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Sample records for antiparkinsonian drug-induced sleepiness

  1. The effect of anti-parkinsonian drugs on chlorpromazine-induced depression of operant behaviour.

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    Székely, J I; Dunai-Kovács, Z; Borsy, J

    1976-01-01

    Rats were conditioned in automatic Skinner boxes on a discrete trial avoidance-escape schedule. The chlorpromazine-induced conditioned reflex inhibition could be reversed by apomorphine and amantadine, but not by atropine, trihexyphenidyl and diethazine. These findings seem to provide an additional tool for differentiating the atropine-like and dopaminergic anti-parkinsonian drugs.

  2. Comparison of the antioxidant potential of antiparkinsonian drugs in different in vitro models

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    Carine Coneglian de Farias

    2014-12-01

    Full Text Available Parkinson's disease (PD is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Furthermore, oxidative stress plays a role in PD, causing or contributing to the neurodegenerative process. Currently PD has only symptomatic treatment and still nothing can be done to stop the degenerative process of the disease. This study aimed to comparatively evaluate the antioxidant capacity of pramipexole, selegeline and amantadine in different in vitrostudies and to offer possible explanations on the molecular antioxidant mechanisms of these drugs. In vitro, the antioxidant capacity of the drugs was assessed by the ability of antiparkinsonian drugs to decrease or scavenge ROS in the neutrophil respiratory burst, ability of antiparkinsonian drugs to donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH•, to scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS+ and evaluation of the ferric reducing antioxidant power (FRAP. This study demonstrated that both pramipexole and selegiline, but not amantadine, have antioxidant effects in vitro by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS+ assay and presenting ferric reduction antioxidant power. This chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs beyond their already recognized mechanism of action.

  3. Severe excessive daytime sleepiness induced by hydroxyurea.

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    Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

    2017-06-01

    Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  4. Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications

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    Cristina Miguelez

    2017-09-01

    Full Text Available The link between the anti-Parkinsonian drug L-3,4-dihydroxyphenylalanine (L-DOPA and the serotonergic (5-HT system has been long established and has received increased attention during the last decade. Most studies have focused on the fact that L-DOPA can be transformed into dopamine (DA and released from 5-HT terminals, which is especially important for the management of L-DOPA-induced dyskinesia. In patients, treatment using L-DOPA also impacts 5-HT neurotransmission; however, few studies have investigated the mechanisms of this effect. The purpose of this review is to summarize the electrophysiological and neurochemical data concerning the effects of L-DOPA on 5-HT cell function. This review will argue that L-DOPA disrupts the link between the electrical activity of 5-HT neurons and 5-HT release as well as that between 5-HT release and extracellular 5-HT levels. These effects are caused by the actions of L-DOPA and DA in 5-HT neurons, which affect 5-HT neurotransmission from the biosynthesis of 5-HT to the impairment of the 5-HT transporter. The interaction between L-DOPA and 5-HT transmission is especially relevant in those Parkinson’s disease (PD patients that suffer dyskinesia, comorbid anxiety or depression, since the efficacy of antidepressants or 5-HT compounds may be affected.

  5. Trends in Antiparkinsonian Medication Use in New Zealand: 1995–2011

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    T. L. Pitcher

    2014-01-01

    Full Text Available Prescribing trends for medications are influenced by development of new drugs, changes in knowledge about efficacy and side effects, and priorities set by funding agencies. Changes in the utilization of antiparkinsonian agents in the outpatient community in New Zealand were investigated by using the national prescription database for the period 1995–2011. The dispensed volumes of antiparkinsonian agents were converted into number of defined daily doses per 1000 inhabitants per day for analysis. Increases in the dispensed volumes of levodopa (77%, amantadine (350%, and catechol-o-methyl transferase inhibitors (326% occurred during the study period. Conversely, decreases in the dispensed volumes of anticholinergics (48%, selegiline (82%, and dopamine agonists (6.2% were observed. New Zealand has seen a substantial increase of the amount of levodopa dispensed in the past 17 years. This increase appears to be related to an increase in the number of people taking the medication. We are unable to extrapolate this change to an increase in the prevalence of PD, given levodopa is used in the treatment of a number of medical conditions. The changes in other antiparkinsonian medications largely reflect changes in availability (increases in entacapone and ropinirole and best practice treatment (declines in anticholinergics, selegiline, and tolcapone.

  6. Assessment of the effects of antihistamine drugs on mood, sleep quality, sleepiness, and dream anxiety.

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    Ozdemir, Pinar Guzel; Karadag, Ayşe Serap; Selvi, Yavuz; Boysan, Murat; Bilgili, Serap Gunes; Aydin, Adem; Onder, Sevda

    2014-08-01

    There are limited comparative studies on classic and new-generation antihistamines that affect sleep quality and mood. The purpose of this study was to determine and compare the effects of classic and new-generation antihistamines on sleep quality, daytime sleepiness, dream anxiety, and mood. Ninety-two patients with chronic pruritus completed study in the dermatology outpatient clinic. Treatments with regular recommended therapeutic doses were administered. The effects of antihistaminic drugs on mood, daytime sleepiness, dream anxiety, and sleep quality were assessed on the first day and 1 month after. Outpatients who received cetirizine and hydroxyzine treatments reported higher scores on the depression, anxiety, and fatigue sub-scales than those who received desloratadine, levocetirizine, and rupatadine. Pheniramine and rupatadine were found to be associated with daytime sleepiness and better sleep quality. UKU side effects scale scores were significantly elevated among outpatients receiving pheniramine. Classic antihistamines increased daytime sleepiness and decreased the sleep quality scores. New-generation antihistamines reduced sleep latency and dream anxiety, and increased daytime sleepiness and sleep quality. Both antihistamines, significantly increased daytime sleepiness and nocturnal sleep quality. Daytime sleepiness was significantly predicted by rupadatine and pheniramine treatment. Cetirizine and hydroxyzine, seem to have negative influences on mood states. Given the extensive use of antihistamines in clinical settings, these results should be more elaborately examined in further studies.

  7. A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat

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    Diack, C.; Ackaert, O.; Ploeger, B. A.; van der Graaf, P. H.; Gurrell, R.; Ivarsson, M.; Fairman, D.

    2011-01-01

    Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across...

  8. Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

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    Ramesh Vijay

    2012-05-01

    Full Text Available Abstract Background Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice. Methods The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice. In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody. Results Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity. Conclusions Taken together

  9. Continuing to drive while sleepy: the influence of sleepiness countermeasures, motivation for driving sleepy, and risk perception.

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    Watling, Christopher N; Armstrong, Kerry A; Obst, Patricia L; Smith, Simon S

    2014-12-01

    Driver sleepiness is a major contributor to road crashes. The current study sought to examine the association between perceptions of effectiveness of six sleepiness countermeasures and their relationship with self-reports of continuing to drive while sleepy among 309 drivers after controlling for the influence of age, sex, motivation for driving sleepy, and risk perception of sleepy driving. The results demonstrate that the variables of age, sex, motivation, and risk perception were significantly associated with self-reports of continuing to drive while sleepy and only one countermeasure was associated with self-reports of continuing to drive while sleepy. Further, it was found that age differences in self-reports of continuing to drive while sleepy was mediated by participants' motivation and risk perception. These findings highlight modifiable factors that could be focused on with interventions that seek to modify drivers' attitudes and behaviours of driving while sleepy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Examining signs of driver sleepiness, usage of sleepiness countermeasures and the associations with sleepy driving behaviours and individual factors.

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    Watling, Christopher N; Armstrong, Kerry A; Radun, Igor

    2015-12-01

    The impairing effect from sleepiness is a major contributor to road crashes. The ability of a sleepy driver to perceive their level of sleepiness is an important consideration for road safety as well as the type of sleepiness countermeasure used by drivers as some sleepiness countermeasures are more effective than others. The aims of the current study were to determine the extent that the signs of driver sleepiness were associated with sleepy driving behaviours, as well as determining which individual factors (demographic, work, driving, and sleep-related factors) were associated with using a roadside or in-vehicle sleepiness countermeasure. A sample of 1518 Australian drivers from the Australian State of New South Wales and the neighbouring Australian Capital Territory took part in the study. The participants' experiences with the signs of sleepiness were reasonably extensive. A number of the early signs of sleepiness (e.g., yawning, frequent eye blinks) were related with continuing to drive while sleepy, with the more advanced signs of sleepiness (e.g., difficulty keeping eyes open, dreamlike state of consciousness) associated with having a sleep-related close call. The individual factors associated with using a roadside sleepiness countermeasure included age (being older), education (tertiary level), difficulties getting to sleep, not continuing to drive while sleepy, and having experienced many signs of sleepiness. The results suggest that these participants have a reasonable awareness and experience with the signs of driver sleepiness. Factors related to previous experiences with sleepiness were associated with implementing a roadside countermeasure. Nonetheless, the high proportions of drivers performing sleepy driving behaviours suggest that concerted efforts are needed with road safety campaigns regarding the dangers of driving while sleepy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. [Circadian rhythm : Influence on Epworth Sleepiness Scale score].

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    Herzog, M; Bedorf, A; Rohrmeier, C; Kühnel, T; Herzog, B; Bremert, T; Plontke, S; Plößl, S

    2017-02-01

    The Epworth Sleepiness Scale (ESS) is frequently used to determine daytime sleepiness in patients with sleep-disordered breathing. It is still unclear whether different levels of alertness induced by the circadian rhythm influence ESS score. The aim of this study is to investigate the influence of circadian rhythm-dependent alertness on ESS performance. In a monocentric prospective noninterventional observation study, 97 patients with suspected sleep-disordered breathing were investigated with respect to daytime sleepiness in temporal relationship to polysomnographic examination and treatment. The Karolinska Sleepiness Scale (KSS) and the Stanford Sleepiness Scale (SSS) served as references for the detection of present sleepiness at three different measurement times (morning, noon, evening), prior to and following a diagnostic polysomnography night as well as after a continuous positive airway pressure (CPAP) titration night (9 measurements in total). The KSS, SSS, and ESS were performed at these times in a randomized order. The KSS and SSS scores revealed a circadian rhythm-dependent curve with increased sleepiness at noon and in the evening. Following a diagnostic polysomnography night, the scores were increased compared to the measurements prior to the night. After the CPAP titration night, sleepiness in the morning was reduced. KSS and SSS reflect the changes in alertness induced by the circadian rhythm. The ESS score war neither altered by the intra-daily nor by the inter-daily changes in the level of alertness. According to the present data, the ESS serves as a reliable instrument to detect the level of daytime sleepiness independently of the circadian rhythm-dependent level of alertness.

  12. Excessive Daytime Sleepiness

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    Yavuz Selvi

    2016-06-01

    Full Text Available Excessive daytime sleepiness is one of the most common sleep-related patient symptoms, with preva-lence in the community estimated to be as high as 18%. Patients with excessive daytime sleepiness may exhibit life threatening road and work accidents, social maladjustment, decreased academic and occupational performance and have poorer health than comparable adults. Thus, excessive daytime sleepiness is a serious condition that requires investigation, diagnosis and treatment primarily. As with most medical condition, evaluation of excessive daytime sleepiness begins a precise history and various objective and subjective tools have been also developed to assess excessive daytime sleepiness. The most common causes of excessive daytime sleepiness are insufficient sleep hygiene, chronic sleep deprivation, medical and psychiatric conditions and sleep disorders, such as obstructive sleep apnea, medications, and narcolepsy. Treatment option should address underlying contributors and promote sleep quantity by ensuring good sleep hygiene. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 114-132

  13. Pavlovian conditioning between co-administered drugs: elicitation of an apomorphine-induced antiparkinsonian response by scopolamine.

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    Carey, R J

    1991-01-01

    Sprague-Dawley rats with unilateral 6-OHDA substantia nigra lesions were given combined scopolamine (0.5 mg/kg IP) and apomorphine (0.05 mg/kg SC) treatments. In this animal model, scopolamine, when administered separately, induces ipsilateral rotation and apomorphine, contralateral rotation. When these drugs are co-administered at 0.5 mg/kg and 0.05 mg/kg dose levels, respectively, animals rotate in the contralateral direction, creating the opportunity for the stimulus effect of scopolamine to become associated with the response effect of apomorphine. In tests with scopolamine (0.5 mg/kg), animals that previously had scopolamine and apomorphine co-administered rotated contralaterally in the test chamber, thereby behaving as if they had received apomorphine. Thus, scopolamine exhibited a functionally acquired conditioned stimulus (CS) property by eliciting the apomorphine response of contralateral rotation as a conditioned response. This acquired CS property was extinguished with separate scopolamine trials and reacquired following one scopolamine-apomorphine co-administration trial.

  14. Daytime sleepiness, sleep habits and occupational accidents among hospital nurses.

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    Suzuki, Kenshu; Ohida, Takashi; Kaneita, Yoshitaka; Yokoyama, Eise; Uchiyama, Makoto

    2005-11-01

    This paper reports a study to determine the prevalence of excessive daytime sleepiness and sleep habits among hospital nurses and to analyse associations between excessive daytime sleepiness and different types of medical error. It has been reported that sleep disorders, and the tiredness and sleepiness brought about by sleep disorders may be associated with occupational accidents. However, to our knowledge, there has so far been no report on associations between sleep disorders, excessive daytime sleepiness in particular, and occupational accidents among hospital nurses. The study was a cross-sectional study targeting 4407 nurses working in eight large general hospitals in Japan. An anonymous self-administered questionnaire was used to investigate their sleep patterns and experience of occupational accidents. The data were collected in 2003. The prevalence of excessive daytime sleepiness among hospital nurses in the present study was 26.0%. A statistically significant relationship was observed between having or not having occupational accidents during the past 12 months and excessive daytime sleepiness. Multiple logistic regression analyses on factors leading to occupational accidents during the past 12 months showed statistically significant associations between (1) drug administration errors and (2) shift work and age, between (1) incorrect operation of medical equipment and (2) excessive daytime sleepiness and age, and between needlestick injuries and age. Excessive daytime sleepiness is an important occupational health issue in hospital nurses. It is possible that occupational policies and health promotion measures, such as a provision of sleep hygiene advice and social support at worksites, would be effective in preventing occupational accidents among hospital nurses.

  15. A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.

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    Diack, C; Ackaert, O; Ploeger, B A; van der Graaf, P H; Gurrell, R; Ivarsson, M; Fairman, D

    2011-12-01

    Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.

  16. Residual sleepiness after N2O sedation: a randomized control trial [ISRCTN88442975

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    Lichtor J Lance

    2004-05-01

    Full Text Available Abstract Background Nitrous oxide (N2O provides sedation for procedures that result in constant low-intensity pain. How long do individuals remain sleepy after receiving N2O? We hypothesized that drug effects would be apparent for an hour or more. Methods This was a randomized, double blind controlled study. On three separate occasions, volunteers (N = 12 received 100% oxygen or 20% or 40% N2O for 30 min. Dependent measures included the multiple sleep latency test (MSLT, a Drug Effects/Liking questionnaire, visual analogue scales, and five psychomotor tests. Repeated measures analysis of variance was performed with drug and time as factors. Results During inhalation, drug effects were apparent based on the questionnaire, visual analogue scales, and psychomotor tests. Three hours after inhaling 100% oxygen or 20% N2O, subjects were sleepier than if they breathed 40% N2O. No other drug effects were apparent 1 hour after inhalation ceased. Patients did not demonstrate increased sleepiness after N2O inhalation. Conclusion We found no evidence for increased sleepiness greater than 1 hour after N2O inhalation. Our study suggests that long-term effects of N2O are not significant.

  17. Risk Factors for Cardiovascular Disease, Metabolic Syndrome and Sleepiness in Truck Drivers

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    Antonio de Padua Mansur

    2015-01-01

    Full Text Available AbstractBackground:Truck driver sleepiness is a primary cause of vehicle accidents. Several causes are associated with sleepiness in truck drivers. Obesity and metabolic syndrome (MetS are associated with sleep disorders and with primary risk factors for cardiovascular diseases (CVD. We analyzed the relationship between these conditions and prevalence of sleepiness in truck drivers.Methods:We analyzed the major risk factors for CVD, anthropometric data and sleep disorders in 2228 male truck drivers from 148 road stops made by the Federal Highway Police from 2006 to 2011. Alcohol consumption, illicit drugs and overtime working hours were also analyzed. Sleepiness was assessed using the Epworth Sleepiness Scale.Results:Mean age was 43.1 ± 10.8 years. From 2006 to 2011, an increase in neck (p = 0.011 and abdominal circumference (p < 0.001, total cholesterol (p < 0.001, triglyceride plasma levels (p = 0.014, and sleepiness was observed (p < 0.001. In addition, a reduction in hypertension (39.6% to 25.9%, p < 0.001, alcohol consumption (32% to 23%, p = 0.033 and overtime hours (52.2% to 42.8%, p < 0.001 was found. Linear regression analysis showed that sleepiness correlated closely with body mass index (β = 0.19, Raj2 = 0.659, p = 0.031, abdominal circumference (β = 0.24, Raj2 = 0.826, p = 0.021, hypertension (β = -0.62, Raj2 = 0.901, p = 0.002, and triglycerides (β = 0.34, Raj2 = 0.936, p = 0.022. Linear multiple regression indicated that hypertension (p = 0.008 and abdominal circumference (p = 0.025 are independent variables for sleepiness.Conclusions:Increased prevalence of sleepiness was associated with major components of the MetS.

  18. Obesity and sleepiness in women with fibromyalgia.

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    de Araújo, Tânia Aparecida; Mota, Maria Carliana; Crispim, Cibele Aparecida

    2015-02-01

    Fibromyalgia (FM) is associated with a number of comorbidities, including chronic widespread pain, fatigue and non-restorative sleep. Evidence has shown that FM is closely associated with overweight and obesity. The objective of the present study was to investigate the relationship between obesity and sleepiness in women with FM. A total of 100 adult female patients with a prior medical diagnosis of FM participated in the study. Body mass, height and waist circumference were measured, and body mass index (BMI) was calculated. The diet quality was evaluated by the Healthy Eating Index. Subjective analyses of daytime sleepiness [Epworth Sleepiness Scale (ESS)] and sleep quality (Pittsburgh Sleep Quality) were performed. An obesity rate of 41 % was found in all women (56.1 % were sleepy and 43.9 % were not, p = 0.04). Obese women showed a greater level of sleepiness when compared with non-obese (10.2 and 7.0, respectively, p = 0.004). Sleepy women showed a greater weight gain after the diagnosis of FM when compared with non-sleepy women (11.7 and 6.4 kg, respectively, p = 0.04). A positive and significant correlation between BMI and sleepiness (r = 0.35, p = 0.02) was also found. In multivariate logistic regression, moderate or severe sleepiness (ESS >12) was associated with obesity (odds ratio 3.44, 95 % CI 1.31-9.01, p = 0.04). These results demonstrate an important association between sleepiness and FM, suggesting that the occurrence of obesity may be involved with sleepiness in these patients.

  19. Measuring subjective sleepiness at work in hospital nurses: validation of a modified delivery format of the Karolinska Sleepiness Scale.

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    Geiger Brown, Jeanne; Wieroney, Margaret; Blair, Lori; Zhu, Shijun; Warren, Joan; Scharf, Steven M; Hinds, Pamela S

    2014-12-01

    Sleepiness during the work shift is common and can be hazardous to workers and, in the case of nurses, to patients under their care. Thus, measuring sleepiness in occupational studies is an important component of workplace health and safety. The Karolinska Sleepiness Scale (KSS) is usually used as a momentary assessment of a respondent's state of sleepiness; however, end-of-shift measurement is sometimes preferred based on the study setting. We assessed the predictive validity of the KSS as an end-of-shift recall measurement, asking for "average" sleepiness over the shift and "highest" level of sleepiness during the shift. Hospital registered nurses (N=40) working 12-h shifts completed an end-of-shift diary over 4 weeks that included the National Aeronautical and Space Administration Task Load Index (NASA-TLX) work intensity items and the KSS (498 shifts over 4 weeks). Vigilant attention was assessed by measuring reaction time, lapses, and anticipations using a 10-min performance vigilance task (PVT) at the end of the shift. The Horne-Ostberg Questionnaire, Epworth Sleepiness Scale, General Sleep Disturbance Scale, and Cleveland Sleep Habits Questionnaire were also collected at baseline to assess factors that could be associated with higher sleepiness. We hypothesized that higher KSS scores would correlate with vigilant attention parameters reflective of sleepiness (slower reaction times and more lapses and anticipations on a performance vigilance task) and also with those factors known to produce higher sleepiness. These factors included the following: (1) working night shifts, especially for those with "morningness" trait; (2) working sequential night shifts; (3) having low physical and mental work demands and low time pressure; (4) having concomitant organic sleep disorders; and (5) having greater "trait" sleepiness (Epworth Sleepiness Scale). Linear mixed models and generalized linear mixed models were used to test associations that could assess the predictive

  20. Caffeine: sleep and daytime sleepiness.

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    Roehrs, Timothy; Roth, Thomas

    2008-04-01

    Caffeine is one of the most widely consumed psychoactive substances and it has profound effects on sleep and wake function. Laboratory studies have documented its sleep-disruptive effects. It clearly enhances alertness and performance in studies with explicit sleep deprivation, restriction, or circadian sleep schedule reversals. But, under conditions of habitual sleep the evidence indicates that caffeine, rather then enhancing performance, is merely restoring performance degraded by sleepiness. The sleepiness and degraded function may be due to basal sleep insufficiency, circadian sleep schedule reversals, rebound sleepiness, and/or a withdrawal syndrome after the acute, over-night, caffeine discontinuation typical of most studies. Studies have shown that caffeine dependence develops at relatively low daily doses and after short periods of regular daily use. Large sample and population-based studies indicate that regular daily dietary caffeine intake is associated with disturbed sleep and associated daytime sleepiness. Further, children and adolescents, while reporting lower daily, weight-corrected caffeine intake, similarly experience sleep disturbance and daytime sleepiness associated with their caffeine use. The risks to sleep and alertness of regular caffeine use are greatly underestimated by both the general population and physicians.

  1. Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness.

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    Philip, Pierre; Sagaspe, Patricia; Prague, Mélanie; Tassi, Patricia; Capelli, Aurore; Bioulac, Bernard; Commenges, Daniel; Taillard, Jacques

    2012-07-01

    To evaluate the effects of acute sleep deprivation and chronic sleep restriction on vigilance, performance, and self-perception of sleepiness. Habitual night followed by 1 night of total sleep loss (acute sleep deprivation) or 5 consecutive nights of 4 hr of sleep (chronic sleep restriction) and recovery night. Eighteen healthy middle-aged male participants (age [(± standard deviation] = 49.7 ± 2.6 yr, range 46-55 yr). Multiple sleep latency test trials, Karolinska Sleepiness Scale scores, simple reaction time test (lapses and 10% fastest reaction times), and nocturnal polysomnography data were recorded. Objective and subjective sleepiness increased immediately in response to sleep restriction. Sleep latencies after the second and third nights of sleep restriction reached levels equivalent to those observed after acute sleep deprivation, whereas Karolinska Sleepiness Scale scores did not reach these levels. Lapse occurrence increased after the second day of sleep restriction and reached levels equivalent to those observed after acute sleep deprivation. A statistical model revealed that sleepiness and lapses did not progressively worsen across days of sleep restriction. Ten percent fastest reaction times (i.e., optimal alertness) were not affected by acute or chronic sleep deprivation. Recovery to baseline levels of alertness and performance occurred after 8-hr recovery night. In middle-aged study participants, sleep restriction induced a high increase in sleep propensity but adaptation to chronic sleep restriction occurred beyond day 3 of restriction. This sleepiness attenuation was underestimated by the participants. One recovery night restores daytime sleepiness and cognitive performance deficits induced by acute or chronic sleep deprivation. Philip P; Sagaspe P; Prague M; Tassi P; Capelli A; Bioulac B; Commenges D; Taillard J. Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness. SLEEP 2012;35(7):997-1002.

  2. Daytime sleepiness in Parkinson's disease: a reappraisal.

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    Valérie Cochen De Cock

    Full Text Available Excessive daytime sleepiness is a frequent complaint in Parkinson's disease (PD; however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson's disease (PD using a wide range of potential predictors.One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT. Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose, depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.

  3. Predicting sleepiness during an awake craniotomy.

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    Itoi, Chihiro; Hiromitsu, Kentaro; Saito, Shoko; Yamada, Ryoji; Shinoura, Nobusada; Midorikawa, Akira

    2015-12-01

    An awake craniotomy is a safe neurological surgical technique that minimizes the risk of brain damage. During the course of this surgery, the patient is asked to perform motor or cognitive tasks, but some patients exhibit severe sleepiness. Thus, the present study investigated the predictive value of a patient's preoperative neuropsychological background in terms of sleepiness during an awake craniotomy. Thirty-seven patients with brain tumor who underwent awake craniotomy were included in this study. Prior to craniotomy, the patient evaluated cognitive status, and during the surgery, each patient's performance and attitude toward cognitive tasks were recorded by neuropsychologists. The present findings showed that the construction and calculation abilities of the patients were moderately correlated with their sleepiness. These results indicate that the preoperative cognitive functioning of patients was related to their sleepiness during the awake craniotomy procedure and that the patients who exhibited sleepiness during an awake craniotomy had previously experienced reduced functioning in the parietal lobe. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Sustainable Reduction of Sleepiness through Salutogenic Self-Care Procedure in Lunch Breaks: A Pilot Study

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    Sebastian Schnieder

    2013-01-01

    Full Text Available The aim of the study was to elucidate the immediate, intermediate, and anticipatory sleepiness reducing effects of a salutogenic self-care procedure called progressive muscle relaxation (PMR, during lunch breaks. The second exploratory aim deals with determining the onset and long-term time course of sleepiness changes. In order to evaluate the intraday range and interday change of the proposed relaxation effects, 14 call center agents were assigned to either a daily 20-minute self-administered PMR or a small talk (ST group during a period of seven months. Participants’ levels of sleepiness were analyzed in a controlled trial using anticipatory, postlunchtime, and afternoon changes of sleepiness as indicated by continuously determined objective reaction time measures (16,464 measurements and self-reports administered five times per day, once per month (490 measurements. Results indicate that, in comparison to ST, the PMR break (a induces immediate, intermediate, and anticipatory reductions in sleepiness; (b these significant effects remarkably show up after one month, and sleepiness continues to decrease for at least another five months. Although further research is required referring to the specific responsible mediating variables, our results suggest that relaxation based lunch breaks are both accepted by employees and provide a sustainable impact on sleepiness.

  5. Improvement in fatigue during Natalizumab treatment is linked to improvement in depression and day-time sleepiness

    Directory of Open Access Journals (Sweden)

    Iris-Katharina ePenner

    2015-02-01

    Full Text Available Background: Fatigue is a frequent symptom in multiple sclerosis (MS and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over one year of treatment with natalizumab. Objective: To evaluate whether fatigue improvement might be directly linked to improved depression and daytime sleepiness. Methods: Patients were assessed regarding fatigue, depression, and daytime sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analysed. Results: After one year of natalizumab treatment, the majority of patients (>92% remained stable or improved in total, motor and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5% and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11% and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. Conclusion: Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.

  6. The effects of armodafinil on objective sleepiness and performance in a shift work disorder sample unselected for objective sleepiness.

    Science.gov (United States)

    Howard, Ryan; Roth, Thomas; Drake, Christopher L

    2014-06-01

    Armodafinil is a medication used to treat excessive sleepiness in individuals with shift work disorder (SWD). In the present study, we investigate whether armodafinil can normalize nocturnal sleepiness in a group of typical SWD patients. Participants were 12 night workers (aged 33.8 ± 8.57 years, 7 female subjects) with excessive sleepiness (≥10 on the Epworth Sleepiness Scale; mean, 14.8 ± 3.16), meeting the International Classification of Sleep Disorders, Second Edition criteria for SWD, with no other sleep or medical disorders verified by polysomnogram. The multiple sleep latency test (MSLT) was not used as an entry criteria. Armodafinil was administered at 10:30 pm in a randomized, double-blind, placebo-controlled, crossover design with experimental nights separated by 1 week. Primary end point was the MSLT, with naps at 1:30, 3:30, 5:30, and 7:30 am. Other study measures included a sleepiness-alertness visual analog scale administered before each nap, and 2 computer-based performance tests evaluating attention and memory. Subjects with SWD had a mean MSLT of 5.3 ± 3.25 minutes, indicating a mean level of pathological sleepiness. Armodafinil significantly improved MSLT score to 11.1 ± 4.79 minutes (P = 0.006). Subjective levels of alertness on the visual analog scale also improved (P = 0.008). For performance, reaction time to central (P = 0.006) and peripheral (P = 0.003) stimuli and free recall memory (P = 0.05) were also improved. Armodafinil 150 mg administered at the beginning of a night shift normalizes nocturnal sleepiness in individuals with SWD unselected for objective sleepiness. Subjective measures of sleepiness and cognitive performance are also improved. This suggests that armodafinil can improve levels of nocturnal alertness to within normal daytime levels in the majority of patients with SWD.

  7. Nintendo Wii Fit-Based Sleepiness Testing is Not Impaired by Contagious Sleepiness

    Directory of Open Access Journals (Sweden)

    Aino Tietäväinen

    2018-06-01

    Full Text Available Sleep deprivation may cause accidents, and it has deteriorating effects on health. A measurement of postural steadiness by a portable and affordable Nintendo Wii Fit balance board can be used to quantify a person's alertness. At work, people are under the influence of their environment—often other people—that may affect their alertness. This work investigates whether sleep deprivation among people is “contagious,” as quantified by sway measures. We measured 21 volunteers' postural steadiness while alert and sleep deprived. During the measurements, a screen placed in front of the participants showed a footage of either alert or sleep-deprived faces. We found a significant difference between the day time and night time steadiness, but found no effect resulting from watching footage of sleep-deprived people. This finding shows that a posturographic sleepiness tester quantifies physiological sleep deprivation, and is insensitive to the influence of social factors. Keywords: contagious sleepiness, portable and affordable sleepiness tester, posturography, social contagion

  8. Are professional drivers less sleepy than non-professional drivers?

    Science.gov (United States)

    Anund, Anna; Ahlström, Christer; Fors, Carina; Åkerstedt, Torbjörn

    2018-01-01

    Objective It is generally believed that professional drivers can manage quite severe fatigue before routine driving performance is affected. In addition, there are results indicating that professional drivers can adapt to prolonged night shifts and may be able to learn to drive without decreased performance under high levels of sleepiness. However, very little research has been conducted to compare professionals and non-professionals when controlling for time driven and time of day. Method The aim of this study was to use a driving simulator to investigate whether professional drivers are more resistant to sleep deprivation than non-professional drivers. Differences in the development of sleepiness (self-reported, physiological and behavioral) during driving was investigated in 11 young professional and 15 non-professional drivers. Results Professional drivers self-reported significantly lower sleepiness while driving a simulator than non-professional drivers. In contradiction, they showed longer blink durations and more line crossings, both of which are indicators of sleepiness. They also drove faster. The reason for the discrepancy in the relation between the different sleepiness indicators for the two groups could be due to more experience to sleepiness among the professional drivers or possibly to the faster speed, which might unconsciously have been used by the professionals to try to counteract sleepiness. Conclusion Professional drivers self-reported significantly lower sleepiness while driving a simulator than non-professional drivers. However, they showed longer blink durations and more line crossings, both of which are indicators of sleepiness, and they drove faster.

  9. Longitudinal change in sleep and daytime sleepiness in postpartum women.

    Directory of Open Access Journals (Sweden)

    Ashleigh J Filtness

    Full Text Available Sleep disruption strongly influences daytime functioning; resultant sleepiness is recognised as a contributing risk-factor for individuals performing critical and dangerous tasks. While the relationship between sleep and sleepiness has been heavily investigated in the vulnerable sub-populations of shift workers and patients with sleep disorders, postpartum women have been comparatively overlooked. Thirty-three healthy, postpartum women recorded every episode of sleep and wake each day during postpartum weeks 6, 12 and 18. Although repeated measures analysis revealed there was no significant difference in the amount of nocturnal sleep and frequency of night-time wakings, there was a significant reduction in sleep disruption, due to fewer minutes of wake after sleep onset. Subjective sleepiness was measured each day using the Karolinska Sleepiness Scale; at the two earlier time points this was significantly correlated with sleep quality but not to sleep quantity. Epworth Sleepiness Scores significantly reduced over time; however, during week 18 over 50% of participants were still experiencing excessive daytime sleepiness (Epworth Sleepiness Score ≥12. Results have implications for health care providers and policy makers. Health care providers designing interventions to address sleepiness in new mothers should take into account the dynamic changes to sleep and sleepiness during this initial postpartum period. Policy makers developing regulations for parental leave entitlements should take into consideration the high prevalence of excessive daytime sleepiness experienced by new mothers, ensuring enough opportunity for daytime sleepiness to diminish to a manageable level prior to reengagement in the workforce.

  10. Daytime Sleepiness among Medical Students in University of Benin ...

    African Journals Online (AJOL)

    ... of daytime sleepiness could be associated with underlying medical/ psychological disorders. There is a need for future studies to address these correlates of day time sleepiness. It is recommended that strategies to enlighten students on sleep hygiene should be pursued. Keywords: Day time sleepiness, medical students, ...

  11. Causes and consequences of sleepiness among college students

    OpenAIRE

    Hershner, Shelley; Chervin,Ron

    2014-01-01

    Shelley D Hershner, Ronald D ChervinDepartment of Neurology, University of Michigan, Ann Arbor, MI, USAAbstract: Daytime sleepiness, sleep deprivation, and irregular sleep schedules are highly prevalent among college students, as 50% report daytime sleepiness and 70% attain insufficient sleep. The consequences of sleep deprivation and daytime sleepiness are especially problematic to college students and can result in lower grade point averages, increased risk of academic failure, compromised ...

  12. Associations among daytime sleepiness, depression and suicidal ideation in Korean adolescents.

    Science.gov (United States)

    Yang, Boksun; Choe, Kwisoon; Park, Youngrye; Kang, Youngmi

    2017-06-09

    The aim of this study was to examine the effects of daytime sleepiness on depression and suicidal ideation in adolescent high-school students. A survey of 538 high school students aged 16-17 years attending two academic schools was conducted. The Epworth Sleepiness Scale (ESS), the Beck Depression Inventory and the Scale for Suicide Ideation were used to assess subjects' daytime sleepiness, depression and suicidal ideation. The mean score for daytime sleepiness was 8.52, which indicates a sleep deficit. Significant positive correlations were found between daytime sleepiness and depression, between daytime sleepiness and suicidal ideation and between depression and suicidal ideation. Gender and depression were significant predictors of suicidal ideation, accounting for 48% of the variance in this measure. Depression acts as a mediator of the relationship between daytime sleepiness and suicidal ideation. High school students in Korea generally have insufficient sleep time and feel sleepy during the day; insufficient sleep during adolescence may be associated with depression and suicidal ideation.

  13. Association of daytime sleepiness with obstructive sleep apnoea and comorbidities varies by sleepiness definition in a population cohort of men.

    Science.gov (United States)

    Adams, Robert J; Appleton, Sarah L; Vakulin, Andrew; Lang, Carol; Martin, Sean A; Taylor, Anne W; McEvoy, R Doug; Antic, Nick A; Catcheside, Peter G; Wittert, Gary A

    2016-10-01

    To determine correlates of excessive daytime sleepiness (EDS) identified with the Epworth Sleepiness Scale (ESS) and a more broad definition, while accounting for obstructive sleep apnoea (OSA) in community dwelling men. Participants of the Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) Study (n = 837, ≥ 40 years) without a prior OSA diagnosis, underwent in-home full unattended polysomnography (PSG, Embletta X100), completed the ESS, STOP questionnaire and Pittsburgh Sleep Quality Index in 2010-2011. In 2007-2010, questionnaires and biomedical assessment (in South Australian public hospital-based clinics) identified medical conditions. An alternate EDS definition (EDSAlt ) consisted of ≥ 2 of 3 problems (feeling sleepy sitting quietly; feeling tired/fatigued/sleepy; trouble staying awake). EDSAlt (30.4%, n = 253), but not ESS ≥ 11 (EDSESS , 12.6%, n = 104), increased significantly across OSA severity and body mass index categories. In adjusted analyses, EDSESS was significantly associated with depression: odds ratio (OR), 95%CI: 2.2 (1.3-3.8) and nocturia: 2.0 (1.3-3.2). EDSAlt was associated with depression, financial stress, relationship, work-life balance problems and associations with nocturia and diabetes were borderline. After excluding men with EDSESS , EDSAlt was associated with oxygen desaturation index (3%) ≥ 16 and the highest arousal index quartile but not with comorbidities. Sleepiness not necessarily leading to dozing, but not ESS ≥ 11, was related to sleep disordered breathing. Clinicians should be alert to (1) differing perspectives of sleepiness for investigation and treatment of OSA, and (2) the presence of depression and nocturia in men presenting with significant Epworth sleepiness regardless of the presence of OSA. © 2016 Asian Pacific Society of Respirology.

  14. Sleep, sleepiness and school start times: a preliminary study.

    Science.gov (United States)

    Dexter, Donn; Bijwadia, Jagdeep; Schilling, Dana; Applebaugh, Gwendolyn

    2003-01-01

    High school students are reported to be excessively sleepy, resulting in decreased academic performance, increased psycho-social problems and increased risk of morbidity and mortality from accidents. Early school start times have been noted to contribute to this problem. This report attempts to confirm the relationship of early school start times with decreased sleep and increased sleepiness. We examined sophomore and junior students in 2 local high schools with different start times and measured the amount of time slept and sleepiness. We found that students at the early start school reported reduced sleep time and more sleepiness than their counterparts at the later starting school. Early school start times are associated with student reports of less sleep and increased sleepiness. Further studies in larger groups are recommended in view of the potential significant impact of sleep deprivation in this age group.

  15. Drug related problems with Antiparkinsonian agents: consumer Internet reports versus published data.

    Science.gov (United States)

    Schröder, Sabrina; Zöllner, York Francis; Schaefer, Marion

    2007-10-01

    There is currently a lack of detailed information concerning drug related problems in the outpatient treatment of Parkinson's disease. Problems associated with drug treatment communicated anonymously in Parkinson's disease online forums were therefore retrospectively searched and documented for 1 year. Based on postings concerning 12 drugs for the treatment of Parkinson's disease, a total of 238 drug related problems were identified and categorised using the Problem Intervention Documentation (PI-Doc). Of these, 153 were adverse drug reactions. Adverse drug reactions associated with the skin were relatively common, but central effects such as cognitive or psychiatric changes, effects on the sleep/waking system and other problems like headache and dizziness accounted for the highest percentage of adverse events. A comparison with data from scientific literature revealed a number of differences. This means that an analysis of online forums detected a number of drug related problems that were otherwise largely invisible. These were mainly associated with the qualitative aspects of treatment such as medication handling, dosage and individual problems concerning adverse events. In addition, the described method of identifying and classifying drug related problems in Internet forums may also be seen as a contribution to the international discussion about consumer reports and pharmacovigilance. The information about adverse drug reactions given by Internet users can be seen as a valuable adjunct to clinical trial data and as being very timely with regard to the event itself. Online forums may be considered as a suitable source of observational information to complement data from randomised clinical trials.

  16. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  17. The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study.

    Science.gov (United States)

    Mineiro, Maria Alexandra; Silva, Pedro Marques da; Alves, Marta; Papoila, Ana Luísa; Marques Gomes, Maria João; Cardoso, João

    2017-12-08

    Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p

  18. Determinants of daytime sleepiness in first-year nursing students: a questionnaire survey.

    Science.gov (United States)

    Huang, Ching-Feng; Yang, Li-Yu; Wu, Li-Min; Liu, Yi; Chen, Hsing-Mei

    2014-06-01

    Daytime sleepiness may affect student learning achievement. Research studies have found that daytime sleepiness is common in university students; however, information regarding the determinants of daytime sleepiness in this population is still lacking. The purpose of this study was to investigate the determinants of daytime sleepiness in first-year nursing students. In particular, we looked for the relationship between perceived symptoms, nocturnal sleep quality, and daytime sleepiness. A cross-sectional and correlational design was employed. Participants were recruited from two nursing programs at an institute of technology located in southern Taiwan. Ninety-three nursing students completed the questionnaires one month after enrollment into their program. Approximately 35% of the participants experienced excessive daytime sleepiness at the beginning of the semester. Six variables (joining a student club, perceived symptoms, daytime dysfunction, sleep disturbances, sleep latency, and subjective sleep quality) were significantly correlated with daytime sleepiness. Among them, daytime dysfunction and perceived symptoms were two major determinants of daytime sleepiness, both accounting for 37.2% of the variance. Daytime sleepiness in students should not be ignored. It is necessary to help first-year students identify and mitigate physical and psychological symptoms early on, as well as improve daytime functioning, to maintain their daytime performance and promote learning achievement. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The wake-promoting drug Modafinil prevents motor impairment in sickness behavior induced by LPS in mice

    DEFF Research Database (Denmark)

    Zager, Adriano; Brandão, Wesley Nogueira; Margatho, Rafael Oliveira

    2018-01-01

    The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present stu...

  20. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  1. Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

    Science.gov (United States)

    Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

    2010-07-21

    The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

  2. Causes and consequences of sleepiness among college students.

    Science.gov (United States)

    Hershner, Shelley D; Chervin, Ronald D

    2014-01-01

    Daytime sleepiness, sleep deprivation, and irregular sleep schedules are highly prevalent among college students, as 50% report daytime sleepiness and 70% attain insufficient sleep. The consequences of sleep deprivation and daytime sleepiness are especially problematic to college students and can result in lower grade point averages, increased risk of academic failure, compromised learning, impaired mood, and increased risk of motor vehicle accidents. This article reviews the current prevalence of sleepiness and sleep deprivation among college students, contributing factors for sleep deprivation, and the role of sleep in learning and memory. The impact of sleep and sleep disorders on academics, grade point average, driving, and mood will be examined. Most importantly, effective and viable interventions to decrease sleepiness and sleep deprivation through sleep education classes, online programs, encouragement of naps, and adjustment of class time will be reviewed. This paper highlights that addressing sleep issues, which are not often considered as a risk factor for depression and academic failure, should be encouraged. Promotion of university and college policies and class schedules that encourage healthy and adequate sleep could have a significant impact on the sleep, learning, and health of college students. Future research to investigate effective and feasible interventions, which disseminate both sleep knowledge and encouragement of healthy sleep habits to college students in a time and cost effective manner, is a priority.

  3. An Assessment of Daytime Sleepiness among Students of the Gulhane Military Faculty of Medicine using the Epworth Sleepiness Scale

    Directory of Open Access Journals (Sweden)

    Soykan sahin

    2014-02-01

    Full Text Available AIM: Sleep is in an active state which is of vital importance for the regeneration of our mental and physical health and which takes up about one third of our lifespan. Sleep disorders are particularly important for specific groups of professionals like health workers. This research aimed to establish the frequency of sleepiness in Gulhane Military Faculty of Medicine students, their sleep disorders and factors that may affect their sleep patterns. It also set out to identify the particular features that may give rise to these conditions and the precautions which may be taken to prevent them. METHOD: The research aimed to encompass all the students in the Gulhane Military Faculty of Medicine. Actual participation was 69% (412/597. The research was cross-sectional with data collected by means of a questionnaire. The Epworth Sleepiness Scale (ESS score was the dependent variable of the research. The sociodemographic particularities of the students, the physical conditions of their sleep area, their habits and health problems were the independent variables. RESULTS: 84.3% of participants stated that they felt the need to sleep during the day. 56.8% of the students revealed that they felt excessively sleepy during the day, whilst 42.8% did not feel excessively sleeply. A significant statistical link has been established in the ESS score between feeling extremely sleepy every day and and #8220;not going to bed at the usual time every day and #8221;, and #8220;not feeling rested upon waking up and #8221;, and #8220;feeling excessively sleepy during the day and #8221; and and #8220;experiencing sleepiness in class because of the classroom environment and #8221; (p<0.05. CONCLUSIONS: Of the students who participated in the survey, 34.5% did experience sleepiness, and this was about 4-6% above the expected level in normal circumstances. The percentage of those Gulhane Military Faculty of Medicine students who had not had enough sleep and those who stated

  4. Sleepiness and alertness in American industries

    International Nuclear Information System (INIS)

    Coleman, R.M.; Dillingham, J.; Dement, W.C.

    1989-01-01

    Recent evidence that industrial accidents may be caused in part by shiftworkers' lack of alertness has caused growing concern at the US Nuclear Regulatory Commission and within the scientific community. The purpose of the study reported in this paper was threefold: (1) Is sleepiness on the job specific to utility plants? (2) Are performance and safety problems caused by sleepiness specific to utility plants? (3) Are specific shift schedules associated with a higher prevalence of sleepiness? Findings indicate sleepiness on the job among shiftworkers is a widespread problem, not limited to the nuclear power industry. The most common solution in American industry is to overstaff each shift and discipline sleeping employees. Results show this is not effective. A more proactive solution is recommended including some of the following: (1) Provide employees education to assist adjustment to shiftwork. (2) Design and implement shift schedules that are more compatible with human physiological capabilities. (3) Allow officially sanctioned napping on shift as is done in Japan. (4) Divide 6-, 8-, or 12-h shifts into smaller blocks of 2 to 3 h of primary duty. (5) make the environment where employees work more conductive to alertness. (6) Develop a firehouse type of schedule where some employees sleep throughout the night, but are awakened if operational problems arise. (7) Provide incentives to employees to adjust their life style to the night shift and reward them with time off

  5. Sleepiness and alertness in American industries

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R.M.; Dillingham, J.; Dement, W.C.

    1989-01-01

    Recent evidence that industrial accidents may be caused in part by shiftworkers' lack of alertness has caused growing concern at the US Nuclear Regulatory Commission and within the scientific community. The purpose of the study reported in this paper was threefold: (1) Is sleepiness on the job specific to utility plants (2) Are performance and safety problems caused by sleepiness specific to utility plants (3) Are specific shift schedules associated with a higher prevalence of sleepiness Findings indicate sleepiness on the job among shiftworkers is a widespread problem, not limited to the nuclear power industry. The most common solution in American industry is to overstaff each shift and discipline sleeping employees. Results show this is not effective. A more proactive solution is recommended including some of the following: (1) Provide employees education to assist adjustment to shiftwork. (2) Design and implement shift schedules that are more compatible with human physiological capabilities. (3) Allow officially sanctioned napping on shift as is done in Japan. (4) Divide 6-, 8-, or 12-h shifts into smaller blocks of 2 to 3 h of primary duty. (5) make the environment where employees work more conductive to alertness. (6) Develop a firehouse type of schedule where some employees sleep throughout the night, but are awakened if operational problems arise. (7) Provide incentives to employees to adjust their life style to the night shift and reward them with time off.

  6. Brazilian air traffic controllers exhibit excessive sleepiness.

    Science.gov (United States)

    Ribas, Valdenilson Ribeiro; de Almeida, Cláudia Ângela Vilela; Martins, Hugo André de Lima; Alves, Carlos Frederico de Oliveira; Alves, Marcos José Pinheiro Cândido; Carneiro, Severino Marcos de Oliveira; Ribas, Valéria Ribeiro; de Vasconcelos, Carlos Augusto Carvalho; Sougey, Everton Botelho; de Castro, Raul Manhães

    2011-01-01

    Excessive sleepiness (ES) is an increased tendency to initiate involuntary sleep for naps at inappropriate times. The objective of this study was to assess ES in air traffic controllers (ATCo). 45 flight protection professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten or more years in the profession (ATCo≥10, n=15) and ATCo with less than ten years in the profession (ATCoair traffic controllers exhibit excessive sleepiness.

  7. Drug: D04641 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Neuropsychiatric agent ... DG01613 ... Xantine-type antiparkinsonian agent ... DG01967 ... Antiparkinson agent ... DG01613 ... Xantine-type antiparki...nsonian agent Cyp substrate ... DG01891 ... CYP1A1 substrate Cyp inhibitor ... DG01915 ... CYP3

  8. Wake-up stroke: Clinical characteristics, sedentary lifestyle, and daytime sleepiness.

    Science.gov (United States)

    Diniz, Deborath Lucia de Oliveira; Barreto, Pedro Rodrigues; Bruin, Pedro Felipe Carvalhedo de; Bruin, Veralice Meireles Sales de

    2016-10-01

    Wake-up stroke (WUS) is defined when the exact time of the beginning of the symptoms cannot be determined, for the deficits are perceived upon awakening. Sleep alterations are important risk factors for stroke and cardiovascular diseases. This study evaluates the characteristics of patients with and without WUS, the presence of daytime sleepiness, and associated risk factors. Patients with ischemic stroke were investigated about the presence of WUS. Clinical and demographic characteristics were evaluated. Stroke severity was studied by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (MRS), and daytime sleepiness severity was studied by the Epworth Sleepiness Scale (ESS). Seventy patients (57.1% men) aged from 32 to 80 years (58.5±13.3) were studied. WUS was observed in 24.3%. Arterial hypertension (67.1%), type 2 diabetes (27.1%), and hyperlipidemia (22.8%) were frequent. Type 2 diabetes and sedentary lifestyle were more common in patients with WUS (p10). No differences were found between patients with and without WUS as regards stroke severity or excessive daytime sleepiness. Patients with excessive daytime sleepiness were younger and had more sedentary lifestyle (psedentary lifestyle. Daytime sleepiness is frequent and is associated with sedentary lifestyle and heavy drinking.

  9. Recommended treatment strategies for patients with excessive daytime sleepiness.

    Science.gov (United States)

    Rosenberg, Russell P

    2015-10-01

    Excessive daytime sleepiness (EDS) is a common and bothersome phenomenon. It can be associated with insufficient sleep syndrome, narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work disorder, Kleine-Levin syndrome, or Parkinson's disease. Once the underlying cause of the excessive sleepiness is determined, clinicians must select the most appropriate behavioral and pharmacologic interventions to reduce daytime sleepiness, alleviate other symptoms, improve functioning, and ensure the safety of patients and those around them. Patient history, adverse effects, and efficacy in specific conditions should be considered in pharmacologic treatment options for patients with EDS. © Copyright 2015 Physicians Postgraduate Press, Inc.

  10. Data-driven prediction of adverse drug reactions induced by drug-drug interactions.

    Science.gov (United States)

    Liu, Ruifeng; AbdulHameed, Mohamed Diwan M; Kumar, Kamal; Yu, Xueping; Wallqvist, Anders; Reifman, Jaques

    2017-06-08

    The expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions. A computational method that provides prospective predictions of potential DDI-induced ADRs will help to identify and mitigate these adverse health effects. We hypothesize that drug-protein interactions can be used as independent variables in predicting ADRs. We constructed drug pair-protein interaction profiles for ~800 drugs using drug-protein interaction information in the public domain. We then constructed statistical models to score drug pairs for their potential to induce ADRs based on drug pair-protein interaction profiles. We used extensive clinical database information to construct categorical prediction models for drug pairs that are likely to induce ADRs via synergistic DDIs and showed that model performance deteriorated only slightly, with a moderate amount of false positives and false negatives in the training samples, as evaluated by our cross-validation analysis. The cross validation calculations showed an average prediction accuracy of 89% across 1,096 ADR models that captured the deleterious effects of synergistic DDIs. Because the models rely on drug-protein interactions, we made predictions for pairwise combinations of 764 drugs that are currently on the market and for which drug-protein interaction information is available. These predictions are publicly accessible at http://avoid-db.bhsai.org . We used the predictive models to analyze broader aspects of DDI-induced ADRs, showing that ~10% of all combinations have the potential to induce ADRs

  11. Pharmacological interventions for sleepiness and sleep disturbances caused by shift work.

    Science.gov (United States)

    Liira, Juha; Verbeek, Jos H; Costa, Giovanni; Driscoll, Tim R; Sallinen, Mikael; Isotalo, Leena K; Ruotsalainen, Jani H

    2014-08-12

    Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst off work, or both, in workers undertaking shift work in their present job and to assess their cost-effectiveness. We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while off work, alertness and sleepiness, or fatigue at work. Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.Melatonin (1 to 10 mg) after the night shift may increase sleep length during daytime sleep (mean difference (MD) 24 minutes, 95% confidence interval (CI) 9.8 to 38.9; seven trials, 263 participants, low quality evidence) and night-time sleep (MD 17 minutes, 95% CI 3.71 to 30.22; three trials, 234 participants, low quality evidence) compared

  12. Distributed neural actions of anti-parkinsonian therapies as revealed by PET

    International Nuclear Information System (INIS)

    Goerendt, I.K.; Mehta, M.A; Stern, J.S.; Brooks, D.J.; Lawrence, A.D.; Odin, P.

    2006-01-01

    There is a limited understanding of how different anti-parkinsonian treatments act at the neuronal systems level. Using positron emission tomography we examined the effects of levodopa and deep brain stimulation of the subthalamic nucleus on patterns of regional cerebral blood flow in patients with Parkinson's disease during a homogenous cognitive-behavioral state rather than during an unspecified resting state. We found that when medicated precuneus, frontal, parietal, cerebellar and midbrain areas were relatively more activated than when stimulated, whereas when stimulated the precentral gyrus, caudate and thalamus were relatively more activated than when medicated. Areas that were activated by both treatments included the temporal gyri, anterior thalamus, and midbrain. Regions of prefrontal cortex showed relatively greater activation in the 'off treatment' conditions of both the medicated and stimulated groups. Our findings suggest that the two treatment methods may lead to symptomatic relief via both common and different sites of action. (author)

  13. [Sleepiness, safety on the road and management of risk].

    Science.gov (United States)

    Garbarino, S; Traversa, F; Spigno, F

    2012-01-01

    Public health studies have shown that sleepiness at the wheel and other risks associated with sleep are responsible for 5% to 30% of road accidents, depending on the type of driver and/or road. In industrialized countries one-fifth of all traffic accidents can be ascribed to sleepiness behind the wheel. Sleep disorders and various common acute and chronic medical conditions together with lifestyles, extended work hours and prolonged wakefulness directly or indirectly affect the quality and quantity of one's sleep increasing the number of workers with sleep debt and staggered hours. These conditions may increase the risk of road accidents. Strategies to reduce this risk of both commercial and non-commercial drivers related to sleepiness include reliable diagnosis and treatment of sleep disorders, management of chronobiological conflicts, adequate catch-up sleep, and countermeasures against sleepiness at the wheel. Road transport safety requires the adoption of occupational health measures, including risk assessment, health education, technical-environmental prevention and health surveillance.

  14. "Sleepiness" is serious in adolescence: Two surveys of 3235 Canadian students

    Directory of Open Access Journals (Sweden)

    Ogilvie Robert

    2006-05-01

    Full Text Available Abstract Background Evidence is growing that sleep problems in adolescents are significant impediments to learning and negatively affect behaviour, attainment of social competence and quality of life. The objectives of the study were to determine the level of sleepiness among students in high school, to identify factors to explain it, and to determine the association between sleepiness and performance in both academic and extracurricular activities Methods A cross-sectional survey of 2201 high school students in the Hamilton Wentworth District School Board and the Near North District School Board in Ontario was conducted in 1998/9. A similar survey was done three years later involving 1034 students in the Grand Erie District School Board in the same Province. The Epworth Sleepiness Scale (ESS was used to measure sleepiness and we also assessed the reliability of this tool for this population. Descriptive analysis of the cohort and information on various measures of performance and demographic data were included. Regression analysis, using the generalised estimating equation (GEE, was utilized to investigate factors associated with risk of sleepiness (ESS>10. Results Seventy per cent of the students had less than 8.5 hours weeknight sleep. Bedtime habits such as a consistent bedtime routine, staying up late or drinking caffeinated beverages before bed were statistically significantly associated with ESS, as were weeknight sleep quantity and gender. As ESS increased there was an increase in the proportion of students who felt their grades had dropped because of sleepiness, were late for school, were often extremely sleepy at school, and were involved in fewer extracurricular activities. These performance measures were statistically significantly associated with ESS. Twenty-three percent of the students felt their grades had dropped because of sleepiness. Most students (58–68% reported that they were "really sleepy" between 8 and 10 A

  15. "Sleepiness" is serious in adolescence: two surveys of 3235 Canadian students.

    Science.gov (United States)

    Gibson, Edward S; Powles, A C Peter; Thabane, Lehana; O'Brien, Susan; Molnar, Danielle Sirriani; Trajanovic, Nik; Ogilvie, Robert; Shapiro, Colin; Yan, Mi; Chilcott-Tanser, Lisa

    2006-05-02

    Evidence is growing that sleep problems in adolescents are significant impediments to learning and negatively affect behaviour, attainment of social competence and quality of life. The objectives of the study were to determine the level of sleepiness among students in high school, to identify factors to explain it, and to determine the association between sleepiness and performance in both academic and extracurricular activities A cross-sectional survey of 2201 high school students in the Hamilton Wentworth District School Board and the Near North District School Board in Ontario was conducted in 1998/9. A similar survey was done three years later involving 1034 students in the Grand Erie District School Board in the same Province. The Epworth Sleepiness Scale (ESS) was used to measure sleepiness and we also assessed the reliability of this tool for this population. Descriptive analysis of the cohort and information on various measures of performance and demographic data were included. Regression analysis, using the generalised estimating equation (GEE), was utilized to investigate factors associated with risk of sleepiness (ESS>10). Seventy per cent of the students had less than 8.5 hours weeknight sleep. Bedtime habits such as a consistent bedtime routine, staying up late or drinking caffeinated beverages before bed were statistically significantly associated with ESS, as were weeknight sleep quantity and gender. As ESS increased there was an increase in the proportion of students who felt their grades had dropped because of sleepiness, were late for school, were often extremely sleepy at school, and were involved in fewer extracurricular activities. These performance measures were statistically significantly associated with ESS. Twenty-three percent of the students felt their grades had dropped because of sleepiness. Most students (58-68%) reported that they were "really sleepy" between 8 and 10 A.M. Sleep deprivation and excessive daytime sleepiness were common

  16. Causes and consequences of sleepiness among college students

    Directory of Open Access Journals (Sweden)

    Hershner SD

    2014-06-01

    Full Text Available Shelley D Hershner, Ronald D ChervinDepartment of Neurology, University of Michigan, Ann Arbor, MI, USAAbstract: Daytime sleepiness, sleep deprivation, and irregular sleep schedules are highly prevalent among college students, as 50% report daytime sleepiness and 70% attain insufficient sleep. The consequences of sleep deprivation and daytime sleepiness are especially problematic to college students and can result in lower grade point averages, increased risk of academic failure, compromised learning, impaired mood, and increased risk of motor vehicle accidents. This article reviews the current prevalence of sleepiness and sleep deprivation among college students, contributing factors for sleep deprivation, and the role of sleep in learning and memory. The impact of sleep and sleep disorders on academics, grade point average, driving, and mood will be examined. Most importantly, effective and viable interventions to decrease sleepiness and sleep deprivation through sleep education classes, online programs, encouragement of naps, and adjustment of class time will be reviewed. This paper highlights that addressing sleep issues, which are not often considered as a risk factor for depression and academic failure, should be encouraged. Promotion of university and college policies and class schedules that encourage healthy and adequate sleep could have a significant impact on the sleep, learning, and health of college students. Future research to investigate effective and feasible interventions, which disseminate both sleep knowledge and encouragement of healthy sleep habits to college students in a time and cost effective manner, is a priority.Keywords: grade point average, GPA, sleep deprivation, academic performance, adolescence, sleep education programs

  17. Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

    Science.gov (United States)

    Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

    2015-01-01

    We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.

  18. Consequences of Split Shift Work in Indian Traffic Police Personnel: Daytime Sleepiness, Stressors and Psychological Distress

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Soni

    2016-12-01

    Full Text Available The present study was aimed to measure the daily routine preference, daytime sleepiness, and psychological distress experiences, because of split shift system job in a sample in traffic police personnel of Raipur city, India. To measure such parameters we used the Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale (ESS, Operational Police Stress Questionnaire (OPSQ, General Health Questionnaire and the Distress. To evaluate differences between age, body mass index, period of service length and drug / alcohol use for all the subjects (traffic police personnel the t-test and chi-square test were used. Total Hundred male traffic police personnel participated and out of which most of them were found to belong in the evening active category. This study also indicates increased prevalence of excessive daytime sleepiness and (EDS high level of psychological distress as measured by the GHQ-12 among few police workers. Moreover, a number of participants reported significant distress levels, when measured with distress thermometer. In nutshell, the study sample suggests adaptive coping strategies of traffic police personnel working in split shift system profession can be attributed to their evening (E-type circadian preferences.

  19. Validation of the Karolinska sleepiness scale against performance and EEG variables.

    Science.gov (United States)

    Kaida, Kosuke; Takahashi, Masaya; Akerstedt, Torbjörn; Nakata, Akinori; Otsuka, Yasumasa; Haratani, Takashi; Fukasawa, Kenji

    2006-07-01

    The Karolinska sleepiness scale (KSS) is frequently used for evaluating subjective sleepiness. The main aim of the present study was to investigate the validity and reliability of the KSS with electroencephalographic, behavioral and other subjective indicators of sleepiness. Participants were 16 healthy females aged 33-43 (38.1+/-2.68) years. The experiment involved 8 measurement sessions per day for 3 consecutive days. Each session contained the psychomotor vigilance task (PVT), the Karolinska drowsiness test (KDT-EEG alpha & theta power), the alpha attenuation test (AAT-alpha power ratio open/closed eyes) and the KSS. Median reaction time, number of lapses, alpha and theta power density and the alpha attenuation coefficients (AAC) showed highly significant increase with increasing KSS. The same variables were also significantly correlated with KSS, with a mean value for lapses (r=0.56). The KSS was closely related to EEG and behavioral variables, indicating a high validity in measuring sleepiness. KSS ratings may be a useful proxy for EEG or behavioral indicators of sleepiness.

  20. Adolescent Sleepiness: Causes and Consequences.

    Science.gov (United States)

    Hansen, Shana L; Capener, Dale; Daly, Christopher

    2017-09-01

    Insufficient sleep duration and poor sleep quality are common among adolescents. The multidimensional causes of insufficient sleep duration and poor sleep quality include biological, health-related, environmental, and lifestyle factors. The most common direct consequence of insufficient and/or poor sleep quality is excessive daytime sleepiness, which may contribute to poor academic performance, behavioral health problems, substance use, and drowsy driving. Evaluation of sleepiness includes a detailed sleep history and sleep diary, with polysomnography only required for the assessment of specific sleep disorders. Management involves encouraging healthy sleep practices such as having consistent bed and wake times, limiting caffeine and electronics at night before bed, and eliminating napping, in addition to treating any existing sleep or medical disorders. [Pediatr Ann. 2017;46(9):e340-e344.]. Copyright 2017, SLACK Incorporated.

  1. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  2. Drug-induced apnea.

    Science.gov (United States)

    Boutroy, M J

    1994-01-01

    Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

  3. Terbinafine-induced lichenoid drug eruption.

    Science.gov (United States)

    Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

    2017-03-01

    Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

  4. Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness.

    Science.gov (United States)

    Watling, Christopher N; Smith, Simon S; Horswill, Mark S

    2014-11-01

    The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15-min nap break or a 15-min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break. Copyright © 2014 Society for Psychophysiological Research.

  5. Sleep disordered breathing and daytime sleepiness are associated with poor academic performance in teenagers. A study using the Pediatric Daytime Sleepiness Scale (PDSS).

    Science.gov (United States)

    Perez-Chada, Daniel; Perez-Lloret, Santiago; Videla, Alejandro J; Cardinali, Daniel; Bergna, Miguel A; Fernández-Acquier, Mariano; Larrateguy, Luis; Zabert, Gustavo E; Drake, Christopher

    2007-12-01

    Inadequate sleep and sleep disordered breathing (SDB) can impair learning skills. Questionnaires used to evaluate sleepiness in adults are usually inadequate for adolescents. We conducted a study to evaluate the performance of a Spanish version of the Pediatric Daytime Sleepiness Scale (PDSS) and to assess the impact of sleepiness and SDB on academic performance. A cross-sectional survey of students from 7 schools in 4 cities of Argentina. A questionnaire with a Spanish version of the PDSS was used. Questions on the occurrence of snoring and witnessed apneas were answered by the parents. Mathematics and language grades were used as indicators of academic performance. The sample included 2,884 students (50% males; age: 13.3 +/- 1.5 years) Response rate was 85%; 678 cases were excluded due to missing data. Half the students slept sleep habits. Insufficient hours of sleep were prevalent in this population. The Spanish version of the PDSS was a reliable tool in middle-school-aged children. Reports of snoring or witnessed apneas and daytime sleepiness as measured by PDSS were independent predictors of poor academic performance.

  6. Drugs of abuse and Parkinson's disease.

    Science.gov (United States)

    Mursaleen, Leah R; Stamford, Jonathan A

    2016-01-04

    The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Mechanistic review of drug-induced steatohepatitis

    International Nuclear Information System (INIS)

    Schumacher, Justin D.; Guo, Grace L.

    2015-01-01

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.

  8. Mechanistic review of drug-induced steatohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, Justin D., E-mail: Justin.d.schumacher@rutgers.edu; Guo, Grace L.

    2015-11-15

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. - Highlights: • Reviewed the mechanisms underlying drug-induced steatohepatitis for many compounds • Mitochondrial dysfunction is critical in the development of drug-induced steatohepatitis. • Majority of drugs that induce steatohepatitis are cationic amphiphilic drugs. • Chemotherapeutics that induce CASH are cationic amphiphilic drugs. • Majority of drugs that induce steatohepatitis are carnitine palmitoyltransferase-I inhibitors.

  9. Sleep and Sleepiness among First-Time Postpartum Parents: A Field- and Laboratory-Based Multimethod Assessment

    Science.gov (United States)

    Insana, Salvatore P.; Montgomery-Downs, Hawley E.

    2012-01-01

    The study aim was to compare sleep, sleepiness, fatigue, and neurobehavioral performance among first-time mothers and fathers during their early postpartum period. Participants were 21 first-time postpartum mother-father dyads (N=42) and seven childless control dyads (N=14). Within their natural environment, participants completed one week of wrist actigraphy monitoring, along with multi-day self-administered sleepiness, fatigue, and neurobehavioral performance measures. The assessment week was followed by an objective laboratory based test of sleepiness. Mothers obtained more sleep compared to fathers, but mothers’ sleep was more disturbed by awakenings. Fathers had greater objectively measured sleepiness than mothers. Mothers and fathers did not differ on subjectively measured sleep quality, sleepiness, or fatigue; however, mothers had worse neurobehavioral performance than fathers. Compared to control dyads, postpartum parents experienced greater sleep disturbance, sleepiness, and sleepiness associated impairments. Study results inform social policy, postpartum sleep interventions, and research on postpartum family systems and mechanisms that propagate sleepiness. PMID:22553114

  10. Traffic crash accidents in Tehran, Iran: Its relation with circadian rhythm of sleepiness.

    Science.gov (United States)

    Sadeghniiat-Haghighi, Khosro; Yazdi, Zohreh; Moradinia, Mohsen; Aminian, Omid; Esmaili, Alireza

    2015-01-01

    Road traffic accidents are one of main problems in Iran. Multiple factors cause traffic accidents and the most important one is sleepiness. This factor, however, is given less attention in our country. Road traffic accidents relevant to sleepiness are studied. In this cross-sectional study, all road traffic accidents relevant to sleepiness, which were reported by police, were studied in Tehran province in 2009. The risk of road traffic accidents due to sleepiness was increased by more than sevenfold (odds ratio = 7.33) in low alertness hours (0:00-6:00) compared to other time of day. The risk of road traffic accidents due to sleepiness was decreased by 0.15-fold (odds ratio = 0.15) in hours with maximum of alertness (18:00-22:00) of circadian rhythm compared to other time of day. The occurrence of road traffic accidents due to sleepiness has significant statistical relations with driving during lowest point of alertness of circadian rhythm.

  11. Excessive daytime sleepiness and metabolic syndrome in men with obstructive sleep apnea: a large cross-sectional study.

    Science.gov (United States)

    Fu, Yiqun; Xu, Huajun; Xia, Yunyan; Qian, Yingjun; Li, Xinyi; Zou, Jianyin; Wang, Yuyu; Meng, Lili; Tang, Xulan; Zhu, Huaming; Zhou, Huiqun; Su, Kaiming; Yu, Dongzhen; Yi, Hongliang; Guan, Jian; Yin, Shankai

    2017-10-03

    Excessive daytime sleepiness is a common symptom in obstructive sleep apnea (OSA). Previous studies have showed that excessive daytime sleepiness is associated with some individual components of metabolic syndrome. We performed a large cross-sectional study to explore the relationship between excessive daytime sleepiness and metabolic syndrome in male OSA patients. A total of 2241 suspected male OSA patients were consecutively recruited from 2007 to 2013. Subjective daytime sleepiness was assessed using the Epworth sleepiness scale. Anthropometric, metabolic, and polysomnographic parameters were measured. Metabolic score was used to evaluate the severity of metabolic syndrome. Among the male OSA patients, most metabolic parameters varied by excessive daytime sleepiness. In the severe group, male OSA patients with excessive daytime sleepiness were more obese, with higher blood pressure, more severe insulin resistance and dyslipidemia than non-sleepy patients. Patients with metabolic syndrome also had a higher prevalence of excessive daytime sleepiness and scored higher on the Epworth sleepiness scale. Excessive daytime sleepiness was independently associated with an increased risk of metabolic syndrome (odds ratio =1.242, 95% confidence interval: 1.019-1.512). No substantial interaction was observed between excessive daytime sleepiness and OSA/ obesity. Excessive daytime sleepiness was related to metabolic disorders and independently associated with an increased risk of metabolic syndrome in men with OSA. Excessive daytime sleepiness should be taken into consideration for OSA patients, as it may be a simple and useful clinical indicator for evaluating the risk of metabolic syndrome.

  12. Non-REM sleep EEG power distribution in fatigue and sleepiness.

    Science.gov (United States)

    Neu, Daniel; Mairesse, Olivier; Verbanck, Paul; Linkowski, Paul; Le Bon, Olivier

    2014-04-01

    The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness. 135 subjects presenting with sleep apnea-hypopnea syndrome (SAHS, n=58) or chronic fatigue syndrome (CFS, n=52) with respective sleepiness or fatigue complaints and a control group (n=25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations. Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2. Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The effect of bright light on sleepiness among rapid-rotating 12-hour shift workers.

    Science.gov (United States)

    Sadeghniiat-Haghighi, Khosro; Yazdi, Zohreh; Jahanihashemi, Hassan; Aminian, Omid

    2011-01-01

    About 20% of workers in industrialized countries are shift workers and more than half of them work on night or rotating shifts. Most night workers complain of sleepiness due to lack of adjustment of the circadian rhythm. In simulated night-work experiments, scheduled exposure to bright light has been shown to reduce these complaints. Our study assessed the effects of bright light exposure on sleepiness during night work in an industrial setting. In a cross-over design, 94 workers at a ceramic factory were exposed to either bright (2500 lux) or normal light (300 lux) during breaks on night shifts. We initiated 20-minute breaks between 24.00 and 02.00 hours. Sleepiness ratings were determined using the Stanford Sleepiness Scale at 22.00, 24.00, 02.00 and 04.00 hours. Under normal light conditions, sleepiness peaked at 02:00 hours. A significant reduction (22% compared to normal light conditions) in sleepiness was observed after workers were exposed to bright light. Exposure to bright light may be effective in reducing sleepiness among night workers.

  14. [Drug-induced oral ulcerations].

    Science.gov (United States)

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  15. The pediatric daytime sleepiness scale (PDSS): sleep habits and school outcomes in middle-school children.

    Science.gov (United States)

    Drake, Christopher; Nickel, Chelsea; Burduvali, Eleni; Roth, Thomas; Jefferson, Catherine; Pietro, Badia

    2003-06-15

    To develop a measure of daytime sleepiness suitable for middle-school children and examine the relationship between daytime sleepiness and school-related outcomes. Self-report questionnaire. Four hundred fifty, 11- to 15-year-old students, from grades 6, 7, and 8 of a public middle school in Dayton, Ohio. A pediatric daytime sleepiness questionnaire was developed using factor analysis of questions regarding sleep-related behaviors. Results of the sleepiness questionnaire were then compared across other variables, including daily sleep patterns, school achievement, mood, and extracurricular activities. Factor analysis on the 13 questions related to daytime sleepiness yielded 1 primary factor ("pediatric daytime sleepiness"; 32% of variance). Only items with factor loadings above .4 were included in the final sleepiness scale. Internal consistency (Chronbach's alpha) for the final 8-item scale was .80. Separate one-way analyses of variance and trend analyses were performed comparing pediatric daytime sleepiness scores at the 5 different levels of total sleep time and academic achievement. Participants who reported low school achievement, high rates of absenteeism, low school enjoyment, low total sleep time, and frequent illness reported significantly higher levels of daytime sleepiness compared to children with better school-related outcomes. The self-report scale developed in the present work is suitable for middle-school-age children and may be useful in future research given its ease of administration and robust psychometric properties. Daytime sleepiness is related to reduced educational achievement and other negative school-related outcomes.

  16. Validation of the Urdu version of the Epworth Sleepiness Scale.

    Science.gov (United States)

    Surani, Asif Anwar; Ramar, Kannan; Surani, Arif Anwar; Khaliqdina, Jehangir Shehryar; Subramanian, Shyam; Surani, Salim

    2012-09-01

    To translate and validate the Epworth Sleepiness Scale (ESS) for use in Urdu-speaking population. The original Epworth Sleepiness Scale was translated into the Urdu version (ESS-Ur) in three phases - translation and back-translation; committee-based translation; and testing in bilingual individuals. The final was subsequently tested on 89 healthy bilingual subjects between February and April, 2010, to assess the validity of the translation compared to the original version. The subjects were students and employees of Dow University of Health Sciences, Karachi. Both English and Urdu versions of the Epworth Sleepiness Scale were administered to 59 (67%) women and 30 (33%) men. The mean composite Epworth score was 7.53 in English language and 7.7 in the Urdu version (p=0.76). The translated version was found to be highly correlated with the original scale (rho=0.938; pscale's Urdu version as an effective tool for measuring daytime sleepiness in Urdu-speaking population. Future studies assessing the validity of such patients with sleep disorders need to be undertaken.

  17. Narcolepsy Patient Presenting as Drop Attack without Emotional Triggering and Subjective Sleepiness

    Directory of Open Access Journals (Sweden)

    Joon Hyun Baek

    2016-12-01

    Full Text Available Narcolepsy type I is characterized by excessive daytime sleepiness (EDS, cataplexy, sleep paralysis, hypnagogic hallucination, and fragmented night-time sleep. Although diagnosis is based on clinical history, it needs to be confirmed by nocturnal polysomnography, followed by a daytime multiple sleep latency test (MSLT. However, EDS, which is the central symptom of the narcolepsy, is unspecific and there could be a disparity between subjective daytime sleepiness and objective daytime sleepiness measured by MSLT. Also, cataplexy, which is the exclusive symptom of narcolepsy, has a wide phenotypical variability and is triggered by a range of stimuli, even without definite identifiable emotional trigger. We report an unusual narcolepsy patient with spontaneous cataplexy, without an identifiable trigger and subjective daytime sleepiness.

  18. Awareness of driving while sleepy and road traffic accidents: prospective study in GAZEL cohort.

    Science.gov (United States)

    Nabi, Hermann; Guéguen, Alice; Chiron, Mireille; Lafont, Sylviane; Zins, Marie; Lagarde, Emmanuel

    2006-07-08

    To examine the association between self assessed driving while sleepy and the risk of serious road traffic accidents (RTAs). Prospective cohort study. France. 13 299 of the 19 894 living members of the GAZEL cohort, workers and recent retirees of a French national utility company followed up since 1989. Frequency of driving while sleepy in the previous 12 months, reported in 2001; rate ratios for serious RTAs in 2001-3, estimated by using generalised linear Poisson regression models with time dependent covariates. The risk of serious RTAs increased proportionally with the frequency of self reported driving while sleepy. After adjustment for sociodemographic characteristics, driving behaviour variables, work conditions, retirement, medical conditions and treatments, depressive symptoms, and sleep disorders, the adjusted rate ratios of serious RTAs for participants who reported driving while sleepy in the previous 12 months "a few times" or "once a month or more often" were 1.5 (95% confidence interval 1.2 to 2.0) and 2.9 (1.3 to 6.3) respectively compared with those who reported not driving while sleepy over the same period. These associations were not explained by any reported sleep disorders. Self assessed driving while sleepy was a powerful predictor of serious RTAs, suggesting that drivers' awareness of their sleepiness while driving is not sufficient to prevent them from having RTAs. Messages on prevention should therefore focus on convincing sleepy drivers to stop driving and sleep before resuming their journey.

  19. Factors affecting drug-induced liver injury: antithyroid drugs as instances

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2014-09-01

    Full Text Available Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

  20. The comparative analysis of antiparkinsonian activity of glycine combined with amantadine in conditions of changing neurosynaptic transmission

    Directory of Open Access Journals (Sweden)

    Mamchur V.I.

    2017-10-01

    Full Text Available Parkinson's disease is traditionally viewed as a disease which affects the human motor sphere. Besides motor manifestations in the clinical picture of the disease, non-motor manifestations with dementia as the most common are present. The purpose of the work – experimental evaluation of the possible antiparkinsonian action of glycine in terms of experimental models of Parkinson's disease equivalents (akinetic-rigid and tremor forms on the background of antiparkinsonian correction by amantadine. Methods: catalepsy model (inhibition of dopaminergic transmission, equivalents of hypokinesia and rigidity states and model of arekolyn tremor (activation of cholinergic transmission that corresponds to parkinsonian tremor on the background of amantadine administration (50 mg/kg, glycine (100 mg/kg and 200 mg/kg and their combined introduction. The research results show a positive dynamic in combined using of amantadine with glycine at a dose of 100 mg/kg and 200 mg/kg, which was is determined by the low percentage of animals with symptoms of catalepsy (50-70% with evaluation criteria of 0.5-1.8 points with maximum possible 6 points. Similar results were obtained in terms of activation of the cholinergic system (arekolyn tremor. Glycine at a dose of 100 mg/kg and 200 mg/kg facilitated to optimization of antitremor action of amantadine, that is registered in increased latent period of tremor, reduction of its duration and intensity attenuation almost by 2,1 times in comparison with indicators of the control group. Thus, studied combinations of amantadine with glycine at a dose of 100 mg/kg and 200 mg/kg are promising in studying of their influence on dementia in Parkinson's syndrome, and this study will be continued.

  1. Daytime Sleepiness in Men During Early Fatherhood: Implications for Work Safety.

    Science.gov (United States)

    Mellor, Gary; Van Vorst, Stephen

    2015-11-01

    This study measured the daytime sleepiness (DS) and work safety of fathers during the first 12 weeks of their babies' lives (i.e., early fatherhood). A questionnaire was developed using the Epworth Sleepiness Scale (ESS), the Safety Behaviour at Work Scale, a self-reported sleep history, and a work-related incident history. Of the 221 participants, the vast majority reported they experienced less than 6 hours of interrupted sleep per night during the 12 weeks of the study, and an increasing frequency and severity of DS. The study also revealed an inverse correlation between ESS and Safety Behaviour at Work scores; fathers were 14% more likely to report a near-miss accident at work at 12 weeks. This study posits that antenatal classes and assessment of fathers' sleepiness at work by occupational health practitioners could assist fathers in reducing daytime sleepiness and mitigating the risk of workplace incidents. © 2015 The Author(s).

  2. Psychometric Properties of Turkish Version of Pediatric Daytime Sleepiness Scale (PDSS-T

    Directory of Open Access Journals (Sweden)

    Murat Bektas, PhD, RN

    2016-03-01

    Conclusions: The study's results showed that PDSS-T is a valid and reliable instrument for detecting Turkish-speaking children's and adolescents' daytime sleepiness. PDSS-T is convenient for professionals to prevent and manage daytime sleepiness.

  3. Drug-induced cholestasis: mechanisms, models, and markers.

    Science.gov (United States)

    Chatterjee, Sagnik; Annaert, Pieter

    2018-04-27

    Drug-induced cholestasis is a risk factor in progression of drug candidates, and poses serious health hazard if not detected before going into human. Intrahepatic accumulation of bile acids (BAs) represents a characteristic phenomenon associated with drug-induced cholestasis. The major challenges in obtaining a complete understanding of drug-induced cholestasis lies in the complexity of BA-mediated toxicity mechanisms and the impact of bile acids at different 'targets' such as transporters, enzymes and nuclear receptors. At the same time, it is not trivial to have a relevant in vitro system that recapitulates these features. In addition, lack of sensitive and early preclinical biomarkers, relevant to the clinical situation, complicates proper detection of drug-induced cholestasis. Significant overlap in biomarker signatures between different mechanisms of drug-induced liver injury (DILI) precludes identification of specific mechanisms. Over the last decade the knowledge gaps in drug-induced cholestasis are closing due to growing mechanistic understanding of BA-mediated toxicity at (patho)physiologically relevant BA concentrations. Significant progress has been made in the mechanistic understanding of drug-induced cholestasis and associated toxicity, biomarkers and susceptibility factors. In addition, novel in vitro models are evolving which provide a holistic understanding of processes underlying drug-induced cholestasis. This review summarizes the challenges and recent understandings about drug-induced cholestasis with a potential path forward. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Recent advances in the treatment and management of excessive daytime sleepiness.

    Science.gov (United States)

    Black, Jed; Duntley, Stephen P; Bogan, Richard K; O'Malley, Mary B

    2007-02-01

    Excessive daytime sleepiness (EDS) is a prevalent complaint among patients in psychiatric care. Patients with conditions of EDS have often been misdiagnosed with depression due to their complaints of lack of energy, poor concentration, memory disturbance, and a reduced interest in life. Impaired alertness associated with EDS can be detrimental to a person's quality of life by causing decreased work performance, self-consciousness, low self esteem, and social isolation. Excessive sleepiness is also associated with various health problems, comorbid medical and psychiatric conditions, and fatal accidents occurring after the driver has fallen asleep at the wheel. Contributing factors leading to EDS range from insufficient sleep hours to central nervous system-mediated debilitating hypersomnolence. Circadian rhythm disorders, sleep disorders such as obstructive sleep apnea and narcolepsy, and medications that cause sleepiness may also contribute to symptoms of EDS. Recognition of the symptoms of sleep deprivation is essential, as many such patients do not have a clear awareness of their own sleepiness. Treatment options, depending upon the condition, include light therapy or appropriate airway management techniques such as nasal continuous positive airway pressure (CPAP). Occasionally, wakefulness-promoting medications are necessary, particularly in patients with narcolepsy. In this expert roundtable supplement, Stephen P. Duntley, MD, reviews the definition and prevalence of EDS and discusses the contributing factors and consequences of daytime sleepiness. Next, Richard K. Bogan, MD, FCCP, gives an overview of the differential diagnosis of EDS and the assessment tools available for identifying sleepiness in symptomatic patients. Finally, Mary B. O'Malley, MD, PhD, reviews treatment of EDS, including counseling on sleep hygiene and duration of sleep, mechanical treatments, bright-light therapy, and wake-promoting medications.

  5. Short Daytime Naps Briefly Attenuate Objectively Measured Sleepiness Under Chronic Sleep Restriction.

    Science.gov (United States)

    Saletin, Jared M; Hilditch, Cassie J; Dement, William C; Carskadon, Mary A

    2017-09-01

    Napping is a useful countermeasure to the negative effects of acute sleep loss on alertness. The efficacy of naps to recover from chronic sleep loss is less well understood. Following 2 baseline nights (10 hours' time-in-bed), participants were restricted to 7 nights of 5-hour sleep opportunity. Ten adults participated in the No-Nap condition, and a further 9 were assigned to a Nap condition with a daily 45-minute nap opportunity at 1300 h. Sleepiness was assessed using the multiple sleep latency test and a visual analogue scale at 2-hour intervals. Both objective and subjective indexes of sleepiness were normalized within subject as a difference from those at baseline prior to sleep restriction. Mixed-effects models examined how the daytime nap opportunity altered sleepiness across the day and across the protocol. Short daytime naps attenuated sleepiness due to chronic sleep restriction for up to 6-8 hours after the nap. Benefits of the nap did not extend late into evening. Subjective sleepiness demonstrated a similar short-lived benefit that emerged later in the day when objective sleepiness already returned to pre-nap levels. Neither measure showed a benefit of the nap the following morning after the subsequent restriction night. These data indicate a short daytime nap may attenuate sleepiness in chronic sleep restriction, yet subjective and objective benefits emerge at different time scales. Because neither measure showed a benefit the next day, the current study underscores the need for careful consideration before naps are used as routine countermeasures to chronic sleep loss. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  6. Excessive Daytime Sleepiness and Unintended Sleep Episodes Associated with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Fatai Salawu

    2015-01-01

    Full Text Available This article looks at the issues of excessive daytime sleepiness and unintended sleep episodes in patients with Parkinson’s disease (PD and explores the reasons why patients might suffer from these symptoms, and what steps could be taken to manage them. During the last decade, understanding of sleep/wake regulation has increased. Several brainstem nuclei and their communication pathways in the ascending arousing system through the hypothalamus and thalamus to the cortex play key roles in sleep disorders. Insomnia is the most common sleep disorder in PD patients, and excessive daytime sleepiness is also common. Excessive daytime sleepiness affects up to 50% of PD patients and a growing body of research has established this sleep disturbance as a marker of preclinical and premotor PD. It is a frequent and highly persistent feature in PD, with multifactorial underlying pathophysiology. Both age and disease-related disturbances of sleep-wake regulation contribute to hypersomnia in PD. Treatment with dopamine agonists also contribute to excessive daytime sleepiness. Effective management of sleep disturbances and excessive daytime sleepiness can greatly improve the quality of life for patients with PD.

  7. Pupillographic assessment of sleepiness in sleep-deprived healthy subjects.

    Science.gov (United States)

    Wilhelm, B; Wilhelm, H; Lüdtke, H; Streicher, P; Adler, M

    1998-05-01

    Spontaneous pupillary-behavior in darkness provides information about a subject's level of sleepiness. In the present work, pupil measurements in complete darkness and quiet have been recorded continuously over 11-minute period with infrared video pupillography at 25 Hz. The data have been analyzed to yield three parameters describing pupil behavior; the power of diameter variation at frequencies below 0.8 Hz (slow changes in pupil size), the pupillary unrest index, and the average pupil size. To investigate the changes of these parameters in sleep deprivation, spontaneous pupillary behavior in darkness was recorded every 2 hours in 13 healthy subjects from 19:00 to 07:00 during forced wakefulness. On each occasion, comparative subjective sleepiness was assessed with a self-rating scale (Stanford Sleepiness Scale, SSS). The power of slow pupillary oscillations (< or = 0.8 Hz) increased significantly and so did the values of SSS, while basic pupil diameter decreased significantly. Slow pupillary oscillations and SSS did not correlate well in general but high values of pupil parameters were always associated with high values in subjective rating. Our results demonstrate a strong relationship between ongoing sleep deprivation and typical changes in the frequency profiles of spontaneous pupillary oscillations and the tendency to instability in pupil size in normals. These findings suggest that the results of pupil data analysis permit an objective measurement of sleepiness.

  8. Drug-induced hepatic injury

    DEFF Research Database (Denmark)

    Friis, Henrik; Andreasen, P B

    1992-01-01

    The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.......5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.......7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected...

  9. The sleepy teenager - diagnostic challenges.

    Science.gov (United States)

    Landtblom, Anne-Marie; Engström, Maria

    2014-01-01

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.

  10. Levothyroxine Improves Subjective Sleepiness in a Euthyroid Patient with Narcolepsy without Cataplexy

    Science.gov (United States)

    Sobol, Danielle L.; Spector, Andrew R.

    2014-01-01

    Objective: We discuss the use of levothyroxine for excessive daytime sleepiness (EDS) and prolonged nocturnal sleep time in a euthyroid patient with narcolepsy. Methods: After failure of first-line narcolepsy treatments, a 48-year-old female began levothyroxine (25 mcg/day). After 12 weeks of treatment, the patient was evaluated for improvement in total sleep time and subjective daytime sleepiness assessed by Epworth Sleepiness Scale (ESS). Results: At baseline, ESS score was 16 and total sleep time averaged 16 h/day. After 12 weeks, ESS was 13 and reported total sleep time was 13 h/day. Conclusions: Levothyroxine improved EDS and total sleep time in a euthyroid patient with narcolepsy without cataplexy after 12 weeks without side effects. Citation: Sobol DL, Spector AR. Levothyroxine improves subjective sleepiness in a euthyroid patient with narcolepsy without cataplexy. J Clin Sleep Med 2014;10(11):1231-1232. PMID:25325591

  11. The comparison of nasal surgery and CPAP on daytime sleepiness in patients with OSAS.

    Science.gov (United States)

    Tagaya, M; Otake, H; Suzuki, K; Yasuma, F; Yamamoto, H; Noda, A; Nishimura, Y; Sone, M; Nakashima, T; Nakata, S

    2017-09-01

    Residual sleepiness after continuous positive airway pressure (CPAP) is a critical problem in some patients with obstructive sleep apnea syndrome (OSAS). However, nasal surgery is likely to reduce daytime sleepiness and feelings of unrefreshed sleep. The aim of this study is to clarify the effects of nasal surgery and CPAP on daytime sleepiness. This is a retrospective and matched-case control study. The participants were consecutive 40 patients with OSAS who underwent nasal surgery (Surgery group) and 40 matched patients who were treated with CPAP (CPAP group). In the Surgery group, although the nasal surgery did not decrease either apnea or hypopnea, it improved oxygenation, the quality of sleep. In the CPAP Group, the CPAP treatment reduced apnea and hypopnea, and improved oxygenation, quality of sleep. The degree of relief from daytime sleepiness was different between the two groups. The improvement of Epworth Sleepiness Scale was more significant in the Surgery Group than those in the CPAP Group (Surgery from 11.0 to 5.1, CPAP from 10.0 to 6.2). These findings suggest that the results of the nasal surgery is more satisfactory for some patients with OSAS than CPAP on daytime sleepiness.

  12. Drug-induced cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Laurinaviciene, Rasa; Holm Sandholdt, Linda; Bygum, Anette

    2017-01-01

    BACKGROUND: An increasing number of drugs have been linked to drug-induced subacute cutaneous lupus erythematosus (DI-SCLE). The recognition and management of DI-SCLE can be challenging, as the condition may be triggered by different classes of drugs after variable lengths of time. OBJECTIVES......: To determine the proportion of patients with cutaneous lupus erythematosus (CLE) whose drugs are an inducing or aggravating factor. MATERIALS & METHODS: We conducted a retrospective chart review of patients diagnosed with CLE at a dermatological department over a 21-year period. We registered clinical......, serological, and histological data with a focus on drug intake. RESULTS: Of 775 consecutive patients with a diagnosis of lupus erythematosus (LE) or suspected LE, a diagnosis of CLE could be confirmed in 448 patients. A total of 130 patients had a drug intake that could suggest DI-SCLE. In 88 cases, a drug...

  13. Adverse drug reactions induced by cardiovascular drugs in outpatients.

    Science.gov (United States)

    Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

    2008-01-01

    Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, PPearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  14. Pharmacological interventions for sleepiness and sleep disturbances caused by shift work

    Directory of Open Access Journals (Sweden)

    Juha Liira

    Full Text Available BACKGROUND: Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. OBJECTIVES: To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst of work, or both, in workers undertaking shift work. METHODS: Search methods: We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. Selection criteria: We included all eligible randomised controlled trials (RCTs, including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while of work, alertness and sleepiness, or fatigue at work. Data collection and analysis: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. MAIN RESULTS: We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined cafeine plus naps to decrease sleepiness or to increase alertness.

  15. Mutual information measures applied to EEG signals for sleepiness characterization.

    Science.gov (United States)

    Melia, Umberto; Guaita, Marc; Vallverdú, Montserrat; Embid, Cristina; Vilaseca, Isabel; Salamero, Manel; Santamaria, Joan

    2015-03-01

    Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders with a great impact on the patient lives. While many studies have been carried out in order to assess daytime sleepiness, the automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on non-linear dynamical analysis of EEG signal was proposed. Multichannel EEG signals were recorded during five maintenance of wakefulness (MWT) and multiple sleep latency (MSLT) tests alternated throughout the day from patients suffering from sleep disordered breathing. A group of 20 patients with excessive daytime sleepiness (EDS) was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60-s EEG windows in waking state. Measures obtained from cross-mutual information function (CMIF) and auto-mutual-information function (AMIF) were calculated in the EEG. These functions permitted a quantification of the complexity properties of the EEG signal and the non-linear couplings between different zones of the scalp. Statistical differences between EDS and WDS groups were found in β band during MSLT events (p-value CMIF measures yielded sensitivity and specificity above 80% and AUC of ROC above 0.85 in classifying EDS and WDS patients. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

  16. Eveningness Chronotype, Daytime Sleepiness, Caffeine Consumption, and Use of Other Stimulants Among Peruvian University Students.

    Science.gov (United States)

    Whittier, Anjalene; Sanchez, Sixto; Castañeda, Benjamín; Sanchez, Elena; Gelaye, Bizu; Yanez, David; Williams, Michelle A

    2014-03-01

    Objectives: The aims of this study were to evaluate patterns of circadian preferences and daytime sleepiness, and to examine the extent to which the consumption of stimulant beverages is associated with daytime sleepiness and evening chronotype among Peruvian college-age students. Methods: A total of 2,581 undergraduate students completed a self-administered comprehensive questionnaire that gathered information about sleep habits, sociodemographic and lifestyle characteristics, and the use of caffeinated beverages. The Morningness-Eveningness Questionnaire (MEQ) and Epworth Sleepiness Scale (ESS) were used to assess chronotype and daytime sleepiness. We used multivariable linear and logistic regression procedures to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations of sleep disorders with sociodemographic and behavioral factors. Results: The prevalence of daytime sleepiness was 35% [95% CI 32.7-36.4] and eveningness chronotype was 10% [95% CI 8.8-11.1%]. Age, sex, cigarette smoking, and alcohol consumption were significantly associated with an evening chronotype. After adjusting for age, sex, smoking, body mass index, and physical activity, students who reported consumption of any stimulant beverages had 1.25 increased odds of excessive daytime sleepiness (OR=1.25 [95% CI 1.03-1.53]) compared with students who did not consume stimulant beverages. Consumption of any stimulant beverages was not statistically significantly associated with being an evening chronotype (OR=1.30 [95% CI 0.86-1.96]). Conclusions: Excessive daytime sleepiness and eveningness chronotype are common among Peruvian college students. MEQ scores were associated with age, sex, smoking, and alcohol consumption. Regular stimulant beverage consumption tended to be positively associated with excessive daytime sleepiness.

  17. Mutual information measures applied to EEG signals for sleepiness characterization

    OpenAIRE

    Melia, Umberto Sergio Pio; Guaita, Marc; Vallverdú Ferrer, Montserrat; Embid, Cristina; Vilaseca, I; Salamero, Manuel; Santamaria, Joan

    2015-01-01

    Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders with a great impact on the patient lives. While many studies have been carried out in order to assess daytime sleepiness, the automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on non-linear dynamical analysis of EEG signal was proposed. Multichannel EEG signals were recorded during five maintenance of wakefulness (MWT) and multiple sleep lat...

  18. Excessive daytime sleepiness in the elderly: association with cardiovascular risk, obesity and depression

    Directory of Open Access Journals (Sweden)

    Johnnatas Mikael Lopes

    2013-12-01

    Full Text Available OBJECTIVE: To observe the relationship between Excessive Daytime Sleepiness (EDS and the presence of risk factors for cardiovascular dysfunction, depression and obesity in the elderly. METHODS: We interviewed 168 elderly from the community of Campina Grande, Paraíba. They were selected according to health districts in the period of 2010. We used the Epworth Sleepiness Scale to diagnose excessive daytime sleepiness (> 10 points; waist circumference for the risk of cardiovascular dysfunction (> 94 or > 80 cm; Geriatric Depression Scale for depression (>10 points and body mass index for obesity (> 25 kg/m2. Association analysis was performed by the Chi-square test adjusted for sex and age group, adopting α < 0.05. RESULTS: One hundred and sixty eight elderly individuals with mean age of 72.34 ± 7.8 years old participated in this study, being 122 (72.6% women. EDS was identified in 53 (31.5% of them; depression, in 72 (42.9%; overweight/obesity, in 95 (64.46%; and risk of cardiovascular dysfunction, in 129 (79.6%. Depressed men (78.6%, p = 0.0005 and risk of cardiovascular dysfunction (57.1%, p = 0.02 were more prone to EDS. In women, only obesity was related to sleepiness (42.1%, p = 0.01. Only those aged between 70 - 79 years old showed association between sleepiness and obesity. CONCLUSION: It was found that obesity for women, and depression and cardiovascular dysfunction risking for men were associated with EDS in the elderly. The variable sex is a confusion condition for the association with sleepiness.

  19. Adverse drug reactions induced by cardiovascular drugs in outpatients

    Directory of Open Access Journals (Sweden)

    Gholami K

    2008-03-01

    Full Text Available Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs induced by this class of medicinal products seems necessary.Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3% patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5% and the lowest rate with Atenolol (3%. Headache was the most frequent detected ADR (23%. Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05. ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05. With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05. Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  20. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias

    Science.gov (United States)

    Cubeddu, Luigi X.

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended. PMID:26926294

  1. Sleepiness, long distance commuting and night work as predictors of driving performance.

    Directory of Open Access Journals (Sweden)

    Lee Di Milia

    Full Text Available Few studies have examined the effect of working night shift and long distance commuting. We examined the association between several sleep related and demographic variables, commuting distance, night work and use of mobile phones on driving performance. We used a prospective design to recruit participants and conducted a telephone survey (n = 649. The survey collected demographic and journey details, work and sleep history and driving performance concerning the day the participant was recruited. Participants also completed the Karolinska Sleepiness Scale and the Epworth Sleepiness Scale. Night workers reported significantly more sleepiness, shorter sleep duration and commuting longer distances. Seven variables were significant predictors of lane crossing. The strongest predictor was acute sleepiness (OR = 5.25, CI, 1.42-19.49, p<0.01 followed by driving ≥150 kms (OR = 3.61, CI, 1.66-7.81, p<0.001, obtaining less than 10 hours sleep in the previous 48 hours (OR = 2.58, CI, 1.03-6.46, p<0.05, driving after night shift (OR = 2.19, CI, 1.24-3.88, p<0.001, being <43 years old (OR = 1.95, CI, 1.11-3.41, p<0.05 and using mobile phones during the journey (OR = 1.90, CI, 1.10-3.27, p<0.05. Sleep related variables, long-distance commuting and night work have a major impact on lane crossing. Several interventions should be considered to reduce the level of sleepiness in night workers.

  2. Sleep and sleepiness among working and non-working high school evening students.

    Science.gov (United States)

    Teixeira, Liliane Reis; Lowden, Arne; Turte, Samantha Lemos; Nagai, Roberta; Moreno, Claudia Roberta de Castro; Latorre, Maria do Rosário Dias de Oliveira; Fischer, Frida Marina

    2007-01-01

    The aim of this study was to evaluate patterns of sleepiness, comparing working and non-working students. The study was conducted on high school students attending evening classes (19:00-22:30 h) at a public school in São Paulo, Brazil. The study group consisted of working (n=51) and non-working (n=41) students, aged 14-21 yrs. The students answered a questionnaire about working and living conditions and reported health symptoms and diseases. For seven consecutive days, actigraphy measurements were recorded, and the students also filled in a sleep diary. Sleepiness ratings were given six times per day, including upon waking and at bedtime, using the Karolinska Sleepiness Scale. Statistical analyses included three-way ANOVA and t-test. The mean sleep duration during weekdays was shorter among workers (7.2 h) than non-workers (8.8 h) (t=4.34; pSleep efficiency was lower on Fridays among non-workers. Working students were moderately sleepier than non-workers during the week and also during class on specific days: Mondays (13:00-15:00 h), Wednesdays (19:00-22:00 h), and Fridays (22:00-00:59 h). The study found that daytime sleepiness of workers is moderately higher in the evening. This might be due to a work effect, reducing the available time for sleep and shortening the sleep duration. Sleepiness and shorter sleep duration can have a negative impact on the quality of life and school development of high school students.

  3. The sleepy teenager - diagnostic challenges

    OpenAIRE

    Anne-Marie eLandtblom; Anne-Marie eLandtblom; Anne-Marie eLandtblom; Anne-Marie eLandtblom; Maria eEngström

    2014-01-01

    The sleepy teenager is a diagnostic challenge because the problems may be physiological or pathological, with behavioural, social and pychological expressions. It is of great importance that health staff that encounter young people with sleep disturbance have good knowledge about the diseases that must be excluded. Narcolepsy, periodic hypersomnia like Kleine Levin syndrome, delayed sleep phase syndrome and obstructive sleep apnoea syndrome, depression and substance use as well as fatigue f...

  4. Drug induced aseptic meningitis

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-29

    Sep 29, 2013 ... Abstract. Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, anal- gesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The pa- tient often ...

  5. Smartphone addiction risk and daytime sleepiness in Korean adolescents.

    Science.gov (United States)

    Chung, Jee Eun; Choi, Soo An; Kim, Ki Tai; Yee, Jeong; Kim, Joo Hee; Seong, Jin Won; Seong, Jong Mi; Kim, Ju Young; Lee, Kyung Eun; Gwak, Hye Sun

    2018-04-06

    Smartphone overuse can cause not only mobility problems in the wrists, fingers and neck but also interference with sleep habits. However, research on smartphone addiction and sleep disturbances is scarce. Therefore, we aimed to investigate daytime sleepiness in association with smartphone addiction risk in Korean adolescents. A cross-sectional survey method was used in this study. The Pediatric Daytime Sleepiness Scale was used to assess daytime sleepiness, and the Korean Smartphone Addiction Proneness Scale index was used to evaluate the degree of risk for smartphone addiction. The analyses were performed in 1796 adolescents using smartphones, including 820 boys and 976 girls. The at-risk smartphone users made up 15.1% of boys and 23.9% of girls. Our multivariate analyses demonstrated that students who were female, consumed alcohol, had lower academic performance, did not feel refreshed in the morning and initiated sleep after 12 am were at a significantly higher risk of smartphone addiction. The at-risk smartphone user group was independently associated with the upper quartile Pediatric Daytime Sleepiness Scale score in students with the following factors: Female gender, alcohol consumption, poor self-perceived health level, initiating sleep after 12 am, longer time taken to fall asleep and duration of night sleep less than 6 h. The quality of sleep in adolescence affects growth, emotional stability and learning skills. Therefore, the management of smartphone addiction seems to be essential for proper sleeping habits. There is a critical need to develop a means of preventing smartphone addiction on a social level. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  6. The Sleepy Teenager – Diagnostic Challenges

    Science.gov (United States)

    Landtblom, Anne-Marie; Engström, Maria

    2014-01-01

    The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character – and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area. PMID:25136329

  7. Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

    Science.gov (United States)

    Arnulf, Isabelle; Neutel, Dulce; Herlin, Bastien; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Cochen de Cock, Valérie; Vidailhet, Marie

    2015-10-01

    To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems. © 2015 Associated Professional Sleep Societies, LLC.

  8. HLA Association with Drug-Induced Adverse Reactions

    Directory of Open Access Journals (Sweden)

    Wen-Lang Fan

    2017-01-01

    Full Text Available Adverse drug reactions (ADRs remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs, such as Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01. The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI. In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

  9. Associations of Subjective Sleep Quality and Daytime Sleepiness With Cognitive Impairment in Adults and Elders With Heart Failure.

    Science.gov (United States)

    Byun, Eeeseung; Kim, Jinyoung; Riegel, Barbara

    2017-01-01

    This study examined the association of subjective nighttime sleep quality and daytime sleepiness with cognitive impairment in 105 adults (sleep quality and daytime sleepiness were measured by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Cognitive impairment was assessed using a neuropsychological battery measuring attention, memory, and processing speed. Multivariate logistic regression was used. In adults, daytime sleepiness was associated with cognitive impairment, whereas poor nighttime sleep quality was associated with cognitive impairment in elders. Age may play an important role in how sleep impacts cognition in persons with heart failure. Improving nighttime sleep quality and daytime sleepiness in this population may improve cognition.

  10. Road accidents caused by sleepy drivers: Update of a Norwegian survey.

    Science.gov (United States)

    Phillips, Ross Owen; Sagberg, Fridulv

    2013-01-01

    The current study tests, updates and expands a model of factors associated with sleepy driving, originally based on a 1997 survey of accident-involved Norwegian drivers (Sagberg, F., 1999. Road accidents caused by drivers falling asleep. Accident Analysis & Prevention 31, 639-649). The aim is to establish a robust model to inform measures to tackle sleepy driving. The original questions on (i) tiredness-related accidents and (ii) incidents of sleep behind the wheel in the last 12 months were again posed in 2003 and 2008, in independent surveys of Norwegian drivers involved in accidents reported to a large insurance company. According to those drivers at-fault for the accident, tiredness or sleepiness behind the wheel contributed to between 1.9 and 3.9 per cent of all types of accident reported to the insurance company across these years. Accident-involved drivers not at fault for the accident reported a reduction in the incidence of sleep behind the wheel for the preceding year, decreasing from 8.3 per cent in 1997 to 2.9 per cent in 2008. The reasons for this are not clear. According to logistic regression analysis of survey responses, the following factors were robustly associated with road accidents involving sleepy driving: driving off the road; good road conditions; longer distance driven since the start of the trip; and fewer years with a driving licence. The following factors are consistently associated with reports of sleep behind the wheel, whether or not it leads to an accident: being male; driving further per year; being younger; and having sleep-related health problems. Taken together these findings suggest that young, inexperienced male drivers who drive long distances may be a suitable target for road safety campaigns aimed at tackling sleepy driving. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Thymus function in drug-induced lupus.

    Science.gov (United States)

    Rubin, R L; Salomon, D R; Guerrero, R S

    2001-01-01

    Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.

  12. Sleepiness and Motor Vehicle Crashes in a Representative Sample of Portuguese Drivers: The Importance of Epidemiological Representative Surveys.

    Science.gov (United States)

    Gonçalves, M; Peralta, A R; Monteiro Ferreira, J; Guilleminault, Christian

    2015-01-01

    Sleepiness is considered to be a leading cause of crashes. Despite the huge amount of information collected in questionnaire studies, only some are based on representative samples of the population. Specifics of the populations studied hinder the generalization of these previous findings. For the Portuguese population, data from sleep-related car crashes/near misses and sleepiness while driving are missing. The objective of this study is to determine the prevalence of near-miss and nonfatal motor vehicle crashes related to sleepiness in a representative sample of Portuguese drivers. Structured phone interviews regarding sleepiness and sleep-related crashes and near misses, driving habits, demographic data, and sleep quality were conducted using the Pittsburgh Sleep Quality Index and sleep apnea risk using the Berlin questionnaire. A multivariate regression analysis was used to determine the associations with sleepy driving (feeling sleepy or falling asleep while driving) and sleep-related near misses and crashes. Nine hundred subjects, representing the Portuguese population of drivers, were included; 3.1% acknowledged falling asleep while driving during the previous year and 0.67% recalled sleepiness-related crashes. Higher education, driving more than 15,000 km/year, driving more frequently between 12:00 a.m. and 6 a.m., fewer years of having a driver's license, less total sleep time per night, and higher scores on the Epworth Sleepiness Scale (ESS) were all independently associated with sleepy driving. Sleepiness-related crashes and near misses were associated only with falling asleep at the wheel in the previous year. Sleep-related crashes occurred more frequently in drivers who had also had sleep-related near misses. Portugal has lower self-reported sleepiness at the wheel and sleep-related near misses than most other countries where epidemiological data are available. Different population characteristics and cultural, social, and road safety specificities may

  13. Excessive daytime sleepiness among depressed patients | Mume ...

    African Journals Online (AJOL)

    Abstract. Background: Excessive daytime sleepiness (EDS) has been reported among depressed patients in many populations. Many depressed patients seek medical attention partly to deal with EDS, but this sleep disorder is often overlooked in clinical practice. Objectives: The objectives of this study were to determine the ...

  14. Excessive daytime sleepiness among depressed patients | Mume ...

    African Journals Online (AJOL)

    Background: Excessive daytime sleepiness (EDS) has been reported among depressed patients in many populations. Many depressed patients seek medical attention partly to deal with EDS, but this sleep disorder is often overlooked in clinical practice. Objectives: The objectives of this study were to determine the ...

  15. Differential sleep, sleepiness, and neurophysiology in the insomnia phenotypes of shift work disorder.

    Science.gov (United States)

    Gumenyuk, Valentina; Belcher, Ren; Drake, Christopher L; Roth, Thomas

    2015-01-01

    To characterize and compare insomnia symptoms within two common phenotypes of Shift Work Disorder. Observational laboratory and field study. Hospital sleep center. 34 permanent night workers. Subjects were classified by Epworth Sleepiness Scale and Insomnia Severity Index into 3 subgroups: asymptomatic controls, alert insomniacs (AI), and sleepy insomniacs (SI). Sleep parameters were assessed by sleep diary. Circadian phase was evaluated by dim-light salivary melatonin onset (DLMO). Objective sleepiness was measured using the multiple sleep latency test (MSLT). Brain activity was measured using the N1 event-related potential (ERP). A tandem repeat in PER3 was genotyped from saliva DNA. (1) AI group showed normal MSLT scores but elevated N1 amplitudes indicating cortical hyperarousal. (2) SI group showed pathologically low MSLT scores but normal N1 amplitudes. (3) AI and SI groups were not significantly different from one another in circadian phase, while controls were significantly phase-delayed relative to both SWD groups. (4) AI showed significantly longer sleep latencies and lower sleep efficiency than controls during both nocturnal and diurnal sleep. SI significantly differed from controls in nocturnal sleep parameters, but differences during diurnal sleep periods were smaller and not statistically significant. (5) Genotype × phenotype χ² analysis showed significant differences in the PER3 VNTR: 9 of 10 shift workers reporting sleepiness in a post hoc genetic substudy were found to carry the long tandem repeat on PER3, while 4 of 14 shift workers without excessive sleepiness carried the long allele. Our results suggest that the sleepy insomnia phenotype is comprehensively explained by circadian misalignment, while the alert insomnia phenotype resembles an insomnia disorder precipitated by shift work. © 2014 Associated Professional Sleep Societies, LLC.

  16. School Maladjustment and External Locus of Control Predict the Daytime Sleepiness of College Students With ADHD.

    Science.gov (United States)

    Langberg, Joshua M; Dvorsky, Melissa R; Becker, Stephen P; Molitor, Stephen J

    2016-09-01

    The primary aim of this study was to evaluate whether school maladjustment longitudinally predicts the daytime sleepiness of college students with ADHD above and beyond symptoms of ADHD and to determine whether internalizing dimensions mediate the relationship between maladjustment and sleepiness. A prospective longitudinal study of 59 college students comprehensively diagnosed with ADHD who completed ratings at the beginning, middle, and end of the school year. School maladjustment at the beginning of the year significantly predicted daytime sleepiness at the end of the year above and beyond symptoms of ADHD. Locus of control mediated the relationship between maladjustment and daytime sleepiness. The significant school maladjustment difficulties that students with ADHD experience following the transition to college may lead to the development of problems with daytime sleepiness, particularly for those students with high external locus of control. This pattern is likely reciprocal, whereby sleep problems in turn result in greater school impairment, reinforcing the idea that life events are outside of one's control. © The Author(s) 2014.

  17. [Health-related consequences of obstructive sleep apnea: daytime sleepiness, accident risk and legal aspects].

    Science.gov (United States)

    Orth, M; Kotterba, S

    2012-04-01

    Daytime sleepiness for any reason leads to impairment of daytime performance and an increased accident rate. The consequences are an increase of illness- and accident-related costs for the health system. Obstructive sleep apnea (OSA) is one of the major reasons for increased daytime sleepiness, especially in professional drivers. The accident frequency in OSA can be significantly reduced by adequate continuous positive airway pressure (CPAP) therapy. Up till now there are no uniform legal regulations about the handling of OSAS patients or patients with daytime sleepiness due to other diseases as far as driving ability is concerned.

  18. The Defense Committees of Sleepy Lagoon: A Convergent Struggle against Fascism, 1942-1944

    Science.gov (United States)

    Barajas, Frank P.

    2006-01-01

    The Sleepy Lagoon Defense Committee originated as an ad hoc committee and evolved to a broad-based movement for legal justice on behalf of seventeen youth convicted of murder and assault charges in connection with the Sleepy Lagoon case in Los Angeles in January 1943. This essay chronicles the multidimensional organizing to shift public opinion in…

  19. Pharmacogenetics of drug-induced arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; van Puijenbroek, Eugene P; Bracke, Madelon

    2006-01-01

    PURPOSE: The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database...... of a spontaneous reporting system for ADRs, using drug-induced arrhythmias as an example. METHODS: Reports of drug-induced arrhythmias to proarrhythmic drugs were selected from the database of the Netherlands Pharmacovigilance Centre (1996-2003). Information on the patient's general practitioner (GP) was obtained...... be included in the study, giving an overall participation rate of 9% (4/45). The main reason for GPs not being willing to participate was lack of time. Variants were identified in KCNH2, SCN5A and KCNE1. CONCLUSIONS: Spontaneous reporting systems for ADRs may be used for pharmacogenetic research. The methods...

  20. Recent Advances in Drug-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Naoko Inomata

    2012-01-01

    Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

  1. Psychometric properties of the Epworth Sleepiness Scale: A factor analysis and item-response theory approach.

    Science.gov (United States)

    Pilcher, June J; Switzer, Fred S; Munc, Alec; Donnelly, Janet; Jellen, Julia C; Lamm, Claus

    2018-04-01

    The purpose of this study is to examine the psychometric properties of the Epworth Sleepiness Scale (ESS) in two languages, German and English. Students from a university in Austria (N = 292; 55 males; mean age = 18.71 ± 1.71 years; 237 females; mean age = 18.24 ± 0.88 years) and a university in the US (N = 329; 128 males; mean age = 18.71 ± 0.88 years; 201 females; mean age = 21.59 ± 2.27 years) completed the ESS. An exploratory-factor analysis was completed to examine dimensionality of the ESS. Item response theory (IRT) analyses were used to provide information about the response rates on the items on the ESS and provide differential item functioning (DIF) analyses to examine whether the items were interpreted differently between the two languages. The factor analyses suggest that the ESS measures two distinct sleepiness constructs. These constructs indicate that the ESS is probing sleepiness in settings requiring active versus passive responding. The IRT analyses found that overall, the items on the ESS perform well as a measure of sleepiness. However, Item 8 and to a lesser extent Item 6 were being interpreted differently by respondents in comparison to the other items. In addition, the DIF analyses showed that the responses between German and English were very similar indicating that there are only minor measurement differences between the two language versions of the ESS. These findings suggest that the ESS provides a reliable measure of propensity to sleepiness; however, it does convey a two-factor approach to sleepiness. Researchers and clinicians can use the German and English versions of the ESS but may wish to exclude Item 8 when calculating a total sleepiness score.

  2. Excessive daytime sleepiness, nocturnal sleep duration and ...

    African Journals Online (AJOL)

    Background and objectives. Short nocturnal sleep duration resulting in sleep debt may be a cause of excessive daytime sleepiness (EDS). Severity of depression (psychopathology) has been found to be directly related to EDS. There is an association between sleep duration and mental health, so there may therefore be an ...

  3. Pharmacological interventions for daytime sleepiness and sleep disorders in Parkinson's disease: Systematic review and meta-analysis.

    Science.gov (United States)

    Rodrigues, Tiago Martins; Castro Caldas, Ana; Ferreira, Joaquim J

    2016-06-01

    Daytime sleepiness and sleep disorders are frequently reported in Parkinson's disease (PD). However, their impact on quality of life has been underestimated and few clinical trials have been performed. We aimed to assess the efficacy and safety of pharmacological interventions for daytime sleepiness and sleep disorders in PD. Systematic review of randomized controlled trials comparing any pharmacological intervention with no intervention or placebo for the treatment of daytime sleepiness and sleep problems in PD patients. Ten studies (n = 338 patients) were included. Four trials addressed interventions for excessive daytime sleepiness. Meta-analysis of the three trials evaluating modafinil showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale (ESS) (- 2.24 points, 95% CI - 3.90 to - 0.57, p sleep Behaviour Disorder (RBD). Single study results suggest that doxepin and YXQN granules might be efficacious, while pergolide may be deleterious for insomnia and that rivastigmine may be used to treat RBD in PD patients. However, there is insufficient evidence to support or refute the efficacy of any of these interventions. No relevant side effects were reported. Whilst providing recommendations, this systematic review depicts the lack of a body of evidence regarding the treatment of sleep disorders in PD patients; hence, further studies are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Drug-induced gynecomastia in children and adolescents

    Science.gov (United States)

    Goldman, Ran D.

    2010-01-01

    ABSTRACT QUESTION I frequently see adolescent boys in my practice with transient gynecomastia. My management includes reassuring the boys and their families; however, I also understand that specific medication, alcohol, and drugs can cause gynecomastia. How common is this phenomenon, and what medications can induce gynecomastia? ANSWER While gynecomastia is a physiologic phenomenon in most newborns and adolescents, it is important to consider pathologic conditions and medications that can cause breast enlargement. Antibiotics, antiulcer drugs, growth hormones, and chemotherapy have been reported to induce gynecomastia. Adolescents who use anabolic steroids, or who abuse alcohol, marijuana, heroin, or amphetamines, should be alerted to the fact that gynecomastia might develop. Treatment of drug-induced gynecomastia includes discontinuation of the offending drug. Very rarely is surgical intervention required. PMID:20393092

  5. Psychometric Properties of Turkish Version of Pediatric Daytime Sleepiness Scale (PDSS-T).

    Science.gov (United States)

    Bektas, Murat; Bektas, Ilknur; Ayar, Dijle; Selekoglu, Yasemin; Ayar, Ugur; Kudubes, Aslı Akdeniz; Altan, Sema Sal; Armstrong, Merry

    2016-03-01

    The aim of the research was to evaluate the psychometric properties of the Pediatric Daytime Sleepiness Scale-Turkish Version (PDSS-T). The researchers chose a study sample of 522 grade 5-11 students. Data were collected using a demographic data collection form and the PDSS-T. Cronbach α for the scale was .79 and Kaiser-Meyer-Olkin coefficient was .78. Item-total correlations for the scale varied between .53 and .73 (p < .001). The indices of model fit were determined to be the root mean square error of approximation at .07, the goodness of fit index at .97, and the comparative fit index at .97. The study's results showed that PDSS-T is a valid and reliable instrument for detecting Turkish-speaking children's and adolescents' daytime sleepiness. PDSS-T is convenient for professionals to prevent and manage daytime sleepiness. Copyright © 2016. Published by Elsevier B.V.

  6. Sleep quality evaluation, chronotype, sleepiness and anxiety of Paralympic Brazilian athletes: Beijing 2008 Paralympic Games.

    Science.gov (United States)

    Silva, Andressa; Queiroz, Sandra Souza; Winckler, Ciro; Vital, Roberto; Sousa, Ronnie Andrade; Fagundes, Vander; Tufik, Sergio; de Mello, Marco Túlio

    2012-02-01

    The objective of this study was to evaluate the sleep quality, sleepiness, chronotype and the anxiety level of Brazilian Paralympics athletes before the 2008 Beijing Paralympic Games. Cross-sectional study. Setting Exercise and Psychobiology Studies Center (CEPE) and Universidade Federal de São Paulo, an urban city in Brazil. A total of 27 Paralympics athletes of both genders (16 men and 11 women) with an average age of 28±6 years who practised athletics (track and field events) were evaluated. Sleep quality was evaluated using the Pittsburgh Scale and the Epworth Sleepiness Scale to evaluate sleepiness. Chronotype was determined by the Horne and Östberg questionnaire and anxiety through the State-Trait Anxiety Inventory. The evaluations were performed in Brazil 10 days before the competition. The study's results demonstrate that 83.3% of the athletes that presented excessive daytime sleepiness also had poor sleep quality. The authors noted that 71.4% were classified into the morning type and 72% of the athletes who presented a medium anxiety level also presented poor sleep quality. Athletes with poor sleep quality showed significantly lower sleep efficiency (p=0.0119) and greater sleep latency (p=0.0068) than athletes with good sleep quality. Athletes who presented excessive daytime sleepiness presented lower sleep efficiency compared to non-sleepy athletes (p=0.0241). The authors conclude that the majority of athletes presented poor sleep quality before the competition. This information should be taken into consideration whenever possible when scheduling rest, training and competition times.

  7. Monitoring sleepiness with on-board electrophysiological recordings for preventing sleep-deprived traffic accidents.

    Science.gov (United States)

    Papadelis, Christos; Chen, Zhe; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Chouvarda, Ioanna; Bekiaris, Evangelos; Maglaveras, Nikos

    2007-09-01

    The objective of this study is the development and evaluation of efficient neurophysiological signal statistics, which may assess the driver's alertness level and serve as potential indicators of sleepiness in the design of an on-board countermeasure system. Multichannel EEG, EOG, EMG, and ECG were recorded from sleep-deprived subjects exposed to real field driving conditions. A number of severe driving errors occurred during the experiments. The analysis was performed in two main dimensions: the macroscopic analysis that estimates the on-going temporal evolution of physiological measurements during the driving task, and the microscopic event analysis that focuses on the physiological measurements' alterations just before, during, and after the driving errors. Two independent neurophysiologists visually interpreted the measurements. The EEG data were analyzed by using both linear and non-linear analysis tools. We observed the occurrence of brief paroxysmal bursts of alpha activity and an increased synchrony among EEG channels before the driving errors. The alpha relative band ratio (RBR) significantly increased, and the Cross Approximate Entropy that quantifies the synchrony among channels also significantly decreased before the driving errors. Quantitative EEG analysis revealed significant variations of RBR by driving time in the frequency bands of delta, alpha, beta, and gamma. Most of the estimated EEG statistics, such as the Shannon Entropy, Kullback-Leibler Entropy, Coherence, and Cross-Approximate Entropy, were significantly affected by driving time. We also observed an alteration of eyes blinking duration by increased driving time and a significant increase of eye blinks' number and duration before driving errors. EEG and EOG are promising neurophysiological indicators of driver sleepiness and have the potential of monitoring sleepiness in occupational settings incorporated in a sleepiness countermeasure device. The occurrence of brief paroxysmal bursts of

  8. In-car countermeasures open window and music revisited on the real road: popular but hardly effective against driver sleepiness.

    Science.gov (United States)

    Schwarz, Johanna F A; Ingre, Michael; Fors, Carina; Anund, Anna; Kecklund, Göran; Taillard, Jacques; Philip, Pierre; Åkerstedt, Torbjörn

    2012-10-01

    This study investigated the effects of two very commonly used countermeasures against driver sleepiness, opening the window and listening to music, on subjective and physiological sleepiness measures during real road driving. In total, 24 individuals participated in the study. Sixteen participants received intermittent 10-min intervals of: (i) open window (2 cm opened); and (ii) listening to music, during both day and night driving on an open motorway. Both subjective sleepiness and physiological sleepiness (blink duration) was estimated to be significantly reduced when subjects listened to music, but the effect was only minor compared with the pronounced effects of night driving and driving duration. Open window had no attenuating effect on either sleepiness measure. No significant long-term effects beyond the actual countermeasure application intervals occurred, as shown by comparison to the control group (n = 8). Thus, despite their popularity, opening the window and listening to music cannot be recommended as sole countermeasures against driver sleepiness. © 2012 European Sleep Research Society.

  9. Drug-induced psoriasis: clinical perspectives

    Directory of Open Access Journals (Sweden)

    Balak DMW

    2017-12-01

    Full Text Available Deepak MW Balak, Enes Hajdarbegovic Department of Dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands Abstract: Exposure to certain drugs can elicit an induction or exacerbation of psoriasis. Although well-conducted systematic studies on drug-related psoriasis are mostly lacking, traditionally strong associations have been documented for beta-blockers, lithium, antimalarial drugs such as (hydroxychloroquine, interferons, imiquimod, and terbinafine. More recently, new associations have been reported for monoclonal antibody- and small-molecule-based targeted therapies used for oncological and immunological indications, such as tumor necrosis factor-alpha antagonists and anti-programmed cell death protein 1 immune checkpoint inhibitors. Recognizing potential drug-related psoriasis is of clinical relevance to allow an optimal management of psoriasis. However, in clinical practice, identifying medication-related exacerbations and induction of psoriasis can be challenging. The clinical and histopathological features of drug-provoked psoriasis may differ little from that of “classical” nondrug-related forms of psoriasis. In addition, the latency period between start of the medication and onset of psoriasis can be significantly long for some drugs. Assessment of the Naranjo adverse drug reaction probability scale could be used as a practical tool to better differentiate drug-related psoriasis. The first step in the management of drug-related psoriasis is cessation and replacement of the offending drug when deemed clinically possible. However, the induced psoriasis skin lesions may persist after treatment withdrawal. Additional skin-directed treatment options for drug-related psoriasis follows the conventional psoriasis treatment guidelines and includes topical steroids and vitamin D analogs, ultraviolet phototherapy, systemic treatments, such as acitretin, methotrexate, and fumaric acid esters, and biological treatments

  10. Person-directed, non-pharmacological interventions for sleepiness at work and sleep disturbances caused by shift work.

    Science.gov (United States)

    Slanger, Tracy E; Gross, J Valérie; Pinger, Andreas; Morfeld, Peter; Bellinger, Miriam; Duhme, Anna-Lena; Reichardt Ortega, Rosalinde Amancay; Costa, Giovanni; Driscoll, Tim R; Foster, Russell G; Fritschi, Lin; Sallinen, Mikael; Liira, Juha; Erren, Thomas C

    2016-08-23

    Shift work is often associated with sleepiness and sleep disorders. Person-directed, non-pharmacological interventions may positively influence the impact of shift work on sleep, thereby improving workers' well-being, safety, and health. To assess the effects of person-directed, non-pharmacological interventions for reducing sleepiness at work and improving the length and quality of sleep between shifts for shift workers. We searched CENTRAL, MEDLINE Ovid, Embase, Web of Knowledge, ProQuest, PsycINFO, OpenGrey, and OSH-UPDATE from inception to August 2015. We also screened reference lists and conference proceedings and searched the World Health Organization (WHO) Trial register. We contacted experts to obtain unpublished data. Randomised controlled trials (RCTs) (including cross-over designs) that investigated the effect of any person-directed, non-pharmacological intervention on sleepiness on-shift or sleep length and sleep quality off-shift in shift workers who also work nights. At least two authors screened titles and abstracts for relevant studies, extracted data, and assessed risk of bias. We contacted authors to obtain missing information. We conducted meta-analyses when pooling of studies was possible. We included 17 relevant trials (with 556 review-relevant participants) which we categorised into three types of interventions: (1) various exposures to bright light (n = 10); (2) various opportunities for napping (n = 4); and (3) other interventions, such as physical exercise or sleep education (n = 3). In most instances, the studies were too heterogeneous to pool. Most of the comparisons yielded low to very low quality evidence. Only one comparison provided moderate quality evidence. Overall, the included studies' results were inconclusive. We present the results regarding sleepiness below. Bright light Combining two comparable studies (with 184 participants altogether) that investigated the effect of bright light during the night on sleepiness during a shift

  11. A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

    Directory of Open Access Journals (Sweden)

    Ratih S. I. Putri

    2016-11-01

    Full Text Available The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t, the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach Cmax (tmax, and the plasma concentration half-life (t1/2. To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%, 95.53% (89.75%–101.68%, and 92.11% (84.35%–100.58% for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

  12. A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.

    Science.gov (United States)

    Putri, Ratih S I; Setiawati, Effi; Aziswan, Syifa A; Ong, Fenny; Tjandrawinata, Raymond R; Susanto, Liana W

    2016-11-18

    The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC 0-t ), the area under the plasma concentration curve extrapolated to infinite time (AUC 0-∞ ), the maximum plasma concentration (C max ), the time to reach C max (t max ), and the plasma concentration half-life (t 1/2 ). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and C max parameters, while t max and t 1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired t -test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC 0-t , AUC 0-∞ , and C max , respectively. There were no statistically significant differences for t max and t 1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

  13. Comparing two versions of the Karolinska Sleepiness Scale (KSS).

    Science.gov (United States)

    Miley, Anna Åkerstedt; Kecklund, Göran; Åkerstedt, Torbjörn

    2016-01-01

    The Karolinska Sleepiness Scale (KSS) is frequently used to study sleepiness in various contexts. However, it exists in two versions, one with labels on every other step (version A), and one with labels on every step (version B) on the 9-point scale. To date, there are no studies examining whether these versions can be used interchangeably. The two versions were here compared in a 24 hr wakefulness study of 12 adults. KSS ratings were obtained every hour, alternating version A and B. Results indicated that the two versions are highly correlated, do not have different response distributions on labeled and unlabeled steps, and that the distributions across all steps have a high level of correspondence (Kappa = 0.73). It was concluded that the two versions are quite similar.

  14. Attention Deficit Hyperactivity Disorder Symptoms, Sleepiness and Accidental Risk in 36140 Regularly Registered Highway Drivers.

    Directory of Open Access Journals (Sweden)

    Pierre Philip

    Full Text Available Attention Deficit Hyperactivity Disorder (ADHD is a frequent neurodevelopmental disorder that increases accidental risk. Recent studies show that some patients with ADHD can also suffer from excessive daytime sleepiness but there are no data assessing the role of sleepiness in road safety in patients with ADHD. We conducted an epidemiological study to explore sleep complaints, inattention and driving risks among automobile drivers.From August to September 2014, 491186 regular highway users were invited to participate in an Internet survey on driving habits. 36140 drivers answered a questionnaire exploring driving risks, sleep complaints, sleepiness at the wheel, ADHD symptoms (Adult ADHD Self-Report Scale and distraction at the wheel. 1.7% of all drivers reported inattention-related driving accidents and 0.3% sleep-related driving accidents in the previous year. 1543 drivers (4.3% reported ADHD symptoms and were more likely to report accidents than drivers without ADHD symptoms (adjusted OR = 1.24, [1.03-1.51], p 15 versus 3.2% of drivers without ADHD symptoms and 20.5% reported severe sleepiness at the wheel versus 7.3%. Drivers with ADHD symptoms reported significantly more sleep-related (adjusted OR = 1.4, [1.21-1.60], p < .0001 and inattention-related (adjusted OR = 1.9, [1.71-2.14], p<0001 near misses than drivers without ADHD symptoms. The fraction of near-misses attributable to severe sleepiness at the wheel was 4.24% for drivers without ADHD symptoms versus 10,35% for drivers with ADHD symptoms.Our study shows that drivers with ADHD symptoms have more accidents and a higher level of sleepiness at the wheel than drivers without ADHD symptoms. Drivers with ADHD symptoms report more sleep-related and inattention-related near misses, thus confirming the clinical importance of exploring both attentional deficits and sleepiness at the wheel in these drivers. Road safety campaigns should be improved to better inform drivers of these accidental

  15. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  16. Tranexamic acid-induced fixed drug eruption

    Directory of Open Access Journals (Sweden)

    Natsuko Matsumura

    2015-01-01

    Full Text Available A 33-year-old male showed multiple pigmented patches on his trunk and extremities after he took tranexamic acid for common cold. He stated that similar eruptions appeared when he was treated with tranexamic acid for influenza 10 months before. Patch test showed positive results at 48 h and 72 h by 1% and 10% tranexamic acid at the lesional skin only. To our knowledge, nine cases of fixed drug eruption induced by tranexamic acid have been reported in Japan. Tranexamic acid is a safe drug and frequently used because of its anti-fibrinolytic and anti-inflammatory effects, but caution of inducing fixed drug eruption should be necessary.

  17. Attention Deficit Hyperactivity Disorder Symptoms, Sleepiness and Accidental Risk in 36140 Regularly Registered Highway Drivers.

    Science.gov (United States)

    Philip, Pierre; Micoulaud-Franchi, Jean-Arthur; Lagarde, Emmanuel; Taillard, Jacques; Canel, Annick; Sagaspe, Patricia; Bioulac, Stéphanie

    2015-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder that increases accidental risk. Recent studies show that some patients with ADHD can also suffer from excessive daytime sleepiness but there are no data assessing the role of sleepiness in road safety in patients with ADHD. We conducted an epidemiological study to explore sleep complaints, inattention and driving risks among automobile drivers. From August to September 2014, 491186 regular highway users were invited to participate in an Internet survey on driving habits. 36140 drivers answered a questionnaire exploring driving risks, sleep complaints, sleepiness at the wheel, ADHD symptoms (Adult ADHD Self-Report Scale) and distraction at the wheel. 1.7% of all drivers reported inattention-related driving accidents and 0.3% sleep-related driving accidents in the previous year. 1543 drivers (4.3%) reported ADHD symptoms and were more likely to report accidents than drivers without ADHD symptoms (adjusted OR = 1.24, [1.03-1.51], p 15) versus 3.2% of drivers without ADHD symptoms and 20.5% reported severe sleepiness at the wheel versus 7.3%. Drivers with ADHD symptoms reported significantly more sleep-related (adjusted OR = 1.4, [1.21-1.60], p attentional deficits and sleepiness at the wheel in these drivers. Road safety campaigns should be improved to better inform drivers of these accidental risks.

  18. Nonacetaminophen Drug-Induced Acute Liver Failure.

    Science.gov (United States)

    Thomas, Arul M; Lewis, James H

    2018-05-01

    Acute liver failure of all causes is diagnosed in between 2000 and 2500 patients annually in the United States. Drug-induced acute liver failure is the leading cause of acute liver failure, accounting for more than 50% of cases. Nonacetaminophen drug injury represents 11% of all cases in the latest registry from the US Acute Liver Failure Study Group. Although rare, acute liver failure is clinically dramatic when it occurs, and requires a multidisciplinary approach to management. In contrast with acetaminophen-induced acute liver failure, non-acetaminophen-induced acute liver failure has a more ominous prognosis with a lower liver transplant-free survival. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate.

    Science.gov (United States)

    Lieu, Christopher A; Venkiteswaran, Kala; Gilmour, Timothy P; Rao, Anand N; Petticoffer, Andrew C; Gilbert, Erin V; Deogaonkar, Milind; Manyam, Bala V; Subramanian, Thyagarajan

    2012-01-01

    Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

  20. Depressive symptoms are associated with daytime sleepiness and subjective sleep quality in dementia with Lewy bodies.

    Science.gov (United States)

    Elder, Greg J; Colloby, Sean J; Lett, Debra J; O'Brien, John T; Anderson, Kirstie N; Burn, David J; McKeith, Ian G; Taylor, John-Paul

    2016-07-01

    Sleep problems and depression are common symptoms in dementia with Lewy bodies (DLB), where patients typically experience subjectively poor sleep quality, fatigue and excessive daytime sleepiness. However, whilst sleep disturbances have been linked to depression, this relationship has not received much attention in DLB. The present cross-sectional study addresses this by examining whether depressive symptoms are specifically associated with subjective sleep quality and daytime sleepiness in DLB, and by examining other contributory factors. DLB patients (n = 32) completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and the 15-item Geriatric Depression Scale (GDS-15). Motor and cognitive functioning was also assessed. Pearson correlations were used to assess the relationship between GDS-15, ESS and PSQI scores. GDS-15 scores were positively associated with both ESS (r = 0.51, p depressive symptoms in DLB. Given the cross-sectional nature of the present study, the directionality of this relationship cannot be determined, although this association did not appear to be mediated by sleep quality or daytime sleepiness. Nevertheless, these findings have clinical relevance; daytime sleepiness or poor sleep quality might indicate depression in DLB, and subsequent work should examine whether the treatment of depression can reduce excessive daytime sleepiness and improve sleep quality in DLB patients. Alternatively, more rigorous screening for sleep problems in DLB might assist the treatment of depression. © 2015 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. © 2015 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

  1. Who is sleepier on the night shift? The influence of bio-psycho-social factors on subjective sleepiness of female nurses during the night shift.

    Science.gov (United States)

    Zion, Nataly; Drach-Zahavy, Anat; Shochat, Tamar

    2018-07-01

    Sleepiness is a common complaint during the night shift and may impair performance. The current study aims to identify bio-psycho-social factors associated with subjective sleepiness during the night shift. Ninety-two female nurses working rotating shifts completed a sociodemographic questionnaire, the Munich ChronoType Questionaire for shift workers, the Pittsburg Sleep Quality Index, and the Pre-sleep Arousal Scale. Subjective sleepiness was measured hourly during two night shifts using the Karolinska Sleepiness Scale, and activity monitors assessed sleep duration 24-h before each shift. Findings showed that increased sleepiness was associated with increased age in nurses with early chronotypes and with more children. High cognitive pre-sleep arousal, but not sleep, was associated with increased sleepiness, especially in late chronotypes. The impact of bio-psycho-social factors on night shift sleepiness is complex, and depends on mutual interactions between these factors. Nurses most prone to increased sleepiness must develop personal strategies for maintaining vigilance on the night shift. Practitioner Summary: This study aims to identify bio-psycho-social factors associated with subjective sleepiness of female nurses during the night shift. Increasing sleepiness was associated with increased age in nurses with early chronotypes and with more children. Increased cognitive pre-sleep arousal, but not sleep, was associated with increased sleepiness, especially in late chronotypes.

  2. Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?

    Science.gov (United States)

    Alves, Eduardo da Silva; Ackel-D'Elia, Carolina; Luz, Gabriela Pontes; Cunha, Thays Crosara Abrahão; Carneiro, Gláucia; Tufik, Sergio; Bittencourt, Lia Rita Azeredo; de Mello, Marco Tulio

    2013-05-01

    Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.

  3. A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias.

    Science.gov (United States)

    Lieu, Christopher A; Kunselman, Allen R; Manyam, Bala V; Venkiteswaran, Kala; Subramanian, Thyagarajan

    2010-08-01

    Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug

  4. Relationship between circadian rhythm amplitude and stability with sleep quality and sleepiness among shift nurses and health care workers.

    Science.gov (United States)

    Jafari Roodbandi, Akram; Choobineh, Alireza; Daneshvar, Somayeh

    2015-01-01

    Sleep is affected by the circadian cycle and its features. Amplitude and stability of circadian rhythm are important parameters of the circadian cycle. This study aims to examine the relationship between amplitude and stability of circadian rhythm with sleep quality and sleepiness. In this cross-sectional research, 315 shift nurses and health care workers from educational hospitals of Kerman University of Medical Sciences (KUMS), Iran, were selected using a random sampling method. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Circadian Type Inventory (CTI) were used to collect the required data. In this study, 83.2% suffered from poor sleep and one-half had moderate and excessive sleepiness. The results showed that flexibility in circadian rhythm stability, job stress and sleepiness are among the factors affecting quality sleep in shift workers. Those whose circadian rhythm amplitude was languid suffered more from sleepiness and those whose circadian stability was flexible had a better sleep. Variables including circadian rhythm stability (flexible/rigid) and amplitude (languid/vigorous) can act as predictive indices in order to employ people in a shift work system so that sleepiness and a drop in quality of sleep are prevented.

  5. Risk of Motor Vehicle Accidents Related to Sleepiness at the Wheel: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Bioulac, Stéphanie; Franchi, Jean-Arthur Micoulaud; Arnaud, Mickael; Sagaspe, Patricia; Moore, Nicholas; Salvo, Francesco; Philip, Pierre

    2017-10-01

    Sleepiness at the wheel is widely believed to be a cause of motor vehicle accidents. Nevertheless, a systematic review of studies investigating this relationship has not yet been published. The objective of this study was to quantify the relationship between sleepiness at the wheel and motor vehicle accidents. A systematic review was performed using Medline, Scopus, and ISI Web of Science. The outcome measure of interest was motor vehicle accident defined as involving four- or two-wheeled vehicles in road traffic, professional and nonprofessional drivers, with or without objective consequences. The exposure was sleepiness at the wheel defined as self-reported sleepiness at the wheel. Studies were included if they provided adjusted risk estimates of motor vehicle accidents related to sleepiness at the wheel. Risk estimates and 95% confidence intervals (95% CIs) were extracted and pooled as odds ratios (ORs) using a random-effect model. Heterogeneity was quantified using Q statistics and the I2 index. The potential causes of heterogeneity were investigated using meta-regressions. Ten cross-sectional studies (51,520 participants), six case-control studies (4904 participants), and one cohort study (13,674 participants) were included. Sleepiness at the wheel was associated with an increased risk of motor vehicle accidents (pooled OR 2.51 [95% CI 1.87; 3.39]). A significant heterogeneity was found between the individual risk estimates (Q = 93.21; I2 = 83%). Sleepiness at the wheel increases the risk of motor vehicle accidents and should be considered when investigating fitness to drive. Further studies are required to explore the nature of this relationship. PROSPERO 2015 CRD42015024805. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  6. Sleepiness and health in midlife women: results of the National Sleep Foundation's 2007 Sleep in America poll.

    Science.gov (United States)

    Chasens, Eileen R; Twerski, Sarah R; Yang, Kyeongra; Umlauf, Mary Grace

    2010-01-01

    The 2007 Sleep in America poll, a random-sample telephone survey, provided data for this study of sleep in community-dwelling women aged 40 to 60 years. The majority of the respondents were post- or perimenopausal, overweight, married or living with someone, and reported good health. A subsample (20%) reported sleepiness that consistently interfered with daily life; the sleepy subsample reported more symptoms of insomnia, restless legs syndrome, obstructive sleep apnea, depression and anxiety, as well as more problems with health-promoting behaviors, drowsy driving, job performance, household duties, and personal relationships. Hierarchical regression showed that sleepiness along with depressive symptoms, medical comorbidities, obesity, and lower education were associated with poor self-rated health, whereas menopause status (pre-, peri- or post-) was not. These results suggest that sleep disruptions and daytime sleepiness negatively affect the daily life of midlife women.

  7. Increased Daytime Sleepiness in Patients with Childhood Craniopharyngioma and Hypothalamic Tumor Involvement: Review of the Literature and Perspectives

    Directory of Open Access Journals (Sweden)

    Hermann L. Müller

    2010-01-01

    Full Text Available Childhood craniopharyngiomas are rare embryogenic malformations of the sellar region, presumably derived from Rathke cleft epithelium. The overall survival rates after neurosurgical intervention and/or irradiation are high (92%. However, the quality of survival is frequently impaired due to endocrine deficiencies, sleep disturbances, daytime sleepiness, and severe obesity caused by hypothalamic lesions. Based on self-assessment using nutritional diaries, caloric intake was similar in patients and BMI-matched controls. Analyses of physical activity by accelerometric measurements showed a markedly lower level of physical activity. Significant daytime sleepiness and disturbances of circadian rhythms have been demonstrated in obese childhood craniopharyngioma patients. Daytime sleepiness and obesity in these patients were both correlated with low nocturnal and early morning melatonin levels. Polysomnographic studies in patients with severe daytime sleepiness revealed sleeping patterns typical for secondary narcolepsy. Reports on a beneficial effect of treatment with central stimulating agents supported the hypothesis that secondary narcolepsy should be considered as a rare cause for severe daytime sleepiness in patients with childhood craniopharyngioma.

  8. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

    Science.gov (United States)

    Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J; Peng, Jie; Turek, Fred W; Marconi, Angelica; Rademaker, Alfred W; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C

    2014-04-01

    Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further

  9. Reliability of a single objective measure in assessing sleepiness.

    Science.gov (United States)

    Sunwoo, Bernie Y; Jackson, Nicholas; Maislin, Greg; Gurubhagavatula, Indira; George, Charles F; Pack, Allan I

    2012-01-01

    To evaluate reliability of single objective tests in assessing sleepiness. Subjects who completed polysomnography underwent a 4-nap multiple sleep latency test (MSLT) the following day. Prior to each nap opportunity on MSLT, subjects performed the psychomotor vigilance test (PVT) and divided attention driving task (DADT). Results of single versus multiple test administrations were compared using the intraclass correlation coefficient (ICC) and adjusted for test administration order effects to explore time of day effects. Measures were explored as continuous and binary (i.e., impaired or not impaired). Community-based sample evaluated at a tertiary, university-based sleep center. 372 adult commercial vehicle operators oversampled for increased obstructive sleep apnea risk. N/A. AS CONTINUOUS MEASURES, ICC WERE AS FOLLOWS: MSLT 0.45, PVT median response time 0.69, PVT number of lapses 0.51, 10-min DADT tracking error 0.87, 20-min DADT tracking error 0.90. Based on binary outcomes, ICC were: MSLT 0.63, PVT number of lapses 0.85, 10-min DADT 0.95, 20-min DADT 0.96. Statistically significant time of day effects were seen in both the MSLT and PVT but not the DADT. Correlation between ESS and different objective tests was strongest for MSLT, range [-0.270 to -0.195] and persisted across all time points. Single DADT and PVT administrations are reliable measures of sleepiness. A single MSLT administration can reasonably discriminate individuals with MSL < 8 minutes. These results support the use of a single administration of some objective tests of sleepiness when performed under controlled conditions in routine clinical care.

  10. "Silent" Sleep Apnea in Dentofacial Deformities and Prevalence of Daytime Sleepiness After Orthognathic and Intranasal Surgery.

    Science.gov (United States)

    Posnick, Jeffrey C; Adachie, Anayo; Singh, Neeru; Choi, Elbert

    2018-04-01

    The purposes of this study were to determine the occurrence of undiagnosed "silent" obstructive sleep apnea (OSA) in dentofacial deformity (DFD) patients at initial surgical presentation and to report on the level of daytime sleepiness in DFD patients with OSA and chronic obstructive nasal breathing (CONB) after undergoing bimaxillary, chin, and intranasal surgery. A retrospective cohort study of patients with a bimaxillary DFD and CONB was implemented. Patients were divided into those with no OSA (group I) and those with OSA (group II). Group II was further subdivided into patients referred with polysomnogram (PSG)-confirmed OSA (group IIa) and those with a diagnosis of OSA only after surgical consultation, airway evaluation, and a positive PSG (group IIb). Group II patients were analyzed at a minimum of 1 year after surgery (range, 1 to 10 years) for daytime sleepiness with the Epworth Sleepiness Scale. Patients with postoperative excessive daytime sleepiness were assessed for risk factors and continued need for OSA treatment. Patients in group II were studied to determine which DFD patterns were most associated with OSA. We compared the prevalence of OSA between our study population and the general population. Two hundred sixty-two patients met the inclusion criteria. Of these, 23% (60 of 262) had PSG-confirmed OSA (group II). This rate was much higher than that found in the general population. Of the patients, 7% (19 of 262) were known to have OSA at initial surgical consultation (group IIa). An additional 16% (41 of 262) were later confirmed by PSG to have OSA (group IIb). Patients with primary mandibular deficiency and short face DFDs were most likely to have OSA (P surgery. A significant association was found between group II patients with postoperative excessive daytime sleepiness ("sleepy" or "very sleepy") and a preoperative body mass index category of overweight (P = .026). Our study found silent OSA to be frequent in the DFD population. The

  11. Sleep habits, excessive daytime sleepiness and school performance in high school students.

    Science.gov (United States)

    Shin, Chol; Kim, Jinkwan; Lee, Sangduck; Ahn, Yongkyu; Joo, Soonjae

    2003-08-01

    A questionnaire survey was carried out to examine the sleep habits and excessive daytime sleepiness (EDS) of 3871 high school students with a mean age of 16.8 years in Korea. The results showed that mean total sleep time was 6.3 h/day for male students and 6.5 h/day for female students, which may be insufficient for adolescence during puberty. The overall prevalence of EDS (defined as an Epworth sleepiness scale score of >10) was 15.9% (14.9% for boys and 18.2% for girls). The prevalence of EDS increased significantly (P performance.

  12. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate

    Directory of Open Access Journals (Sweden)

    Christopher A. Lieu

    2012-01-01

    Full Text Available Chronic treatment with levodopa (LD in Parkinson's disease (PD can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD, and LD+CD in hemiparkinsonian (HP monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR and subthalamic nucleus (STN in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

  13. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  14. Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up.

    Science.gov (United States)

    Mauri, M C; Di Pace, C; Reggiori, A; Paletta, S; Colasanti, A

    2017-10-01

    The study reports a follow-up assessment of 48 patients with concomitant drug abuse at the first admission for psychosis. We focused on the diagnostic distinction between primary psychosis with concomitant drug abuse and drug induced psychosis, to observe whether the diagnoses are stable over time and whether the clinical course significantly differs. The study examined 25 primary psychotic disorder with comorbid drug abuse and 23 drug-induced psychotic disorder patients. Diagnostic and psychopathological assessments were made at baseline and at follow-up. Mean follow-up period was 4.96 years. Patients with comorbid Drug Abuse exhibited higher scores in the item Unusual Content of Thought at baseline than drug-induced psychotic disorder patients: 5.48 vs 4.39 while the two patients groups did not differ in any of the BPRS items evaluated at follow-up. The primary psychosis with comorbid drug abuse and the substance induced psychosis groups were similar regarding diagnostic stability, and a diagnosis of schizophrenia at follow-up occurred similarly. There was no evidence that Drug Induced psychotic patients' symptoms tend to improve more after cessation of drug abuse. An earlier age of onset was found in primary psychotic patients, particularly for patients diagnosed as affected by schizophrenia at follow up. These results might reflect the uncertainty of the distinction between Primary and Drug Induced Psychosis and the difficulties in applying the DSM IV-TR criteria for diagnosing comorbid drug use disorders and psychotic disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. [SLEEP QUALITY, EXCESSIVE DAYTIME SLEEPINESS AND INSOMNIA IN CHILEAN PARALYMPIC ATHLETES].

    Science.gov (United States)

    Durán Agüero, Samuel; Arroyo Jofre, Patricio; Varas Standen, Camila; Herrera-Valenzuela, Tomas; Moya Cantillana, Cristobal; Pereira Robledo, Rodolfo; Valdés-Badilla, Pablo

    2015-12-01

    the sleep takes part in diverse biological and physiological functions, associating his restriction, with minor performance in the sport, nevertheless the quantity and quality of sleep is not known in paralympic athletes. to determine the sleep quality, insomnia and excessive daytime sleepiness in Chilean paralympic athletes. descriptive transverse Study, the sample included 33 paralympic athletes (24.2% women), those who were practicing swimming, tennis of table, football 5, powerlifting and tennis chair. The studied variables measured up across two surveys of dream: the Questionnaire of Insomnia and the Pittsburgh Sleep Quality Index. the paralympic athletes sleep were 6.9 } 1.4 hours, 27.7% presents daytime sleepiness, 69.6 % insomnia (Survey of insomnia =7), whereas 78.7 % exhibits a bad sleep quality. The age showed a positive correlation with latency to the sleep (r=0.417 *), the insomnia with latency to the sleep (r=0.462 **), the Pittsburg score was correlated negatively by the sleep duration (r =-0.323) and latency to the sleep is correlated positively by the Pittsburgh score (r=0.603 **). the chilean paralympic athletes, present a low sleep quality, insomnia and excessive daytime sleepiness, situation that might influence negatively the sports performance. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  16. Sleep and sleepiness in children with attention deficit / hyperactivity disorder and controls.

    Science.gov (United States)

    Wiebe, Sabrina; Carrier, Julie; Frenette, Sonia; Gruber, Reut

    2013-02-01

    The present study assessed the association between habitual sleep patterns and one night of PSG measured sleep with daytime sleepiness in children with ADHD and typically developing children. Eighty-two children (26 ADHD, 56 typically developing children), between 7 and 11 years, had nighttime sleep recorded using actigraphy over five nights (habitual sleep patterns) and polysomnography during one night (immediate sleep patterns), both within their home environments. Daytime sleepiness was examined using the multiple sleep latency test within a controlled laboratory setting the following day. Using Spearman correlations, the relationships between mean sleep latencies on the multiple sleep latency test and scores on a modified Epworth Sleepiness Scale with polysomnographic measures of sleep quality and architecture and with actigraphic sleep quality measures were examined. Longer sleep latency, measured using polysomnography and actigraphy, was related to longer mean sleep latencies on the multiple sleep latency test in typically developing participants, whereas actigraphic measures of sleep restlessness (time awake and activity during the night), as well as time in slow-wave sleep, were positively related to mean sleep latency on the multiple sleep latency test in children with ADHD. These results show a differential relationship for children with ADHD and typically developing children between habitual and immediate sleep patterns with daytime sleepiness and suggest that problems initiating and maintaining sleep may be present both in nighttime and daytime sleep. © 2012 European Sleep Research Society.

  17. Sleepiness and sleep-disordered breathing in truck drivers : risk analysis of road accidents.

    Science.gov (United States)

    Catarino, Rosa; Spratley, Jorge; Catarino, Isabel; Lunet, Nuno; Pais-Clemente, Manuel

    2014-03-01

    Portugal has one of the highest road traffic fatality rates in Europe. A clear association between sleep-disordered breathing (SDB) and traffic accidents has been previously demonstrated. This study aimed to determine prevalence of excessive daytime sleepiness (EDS) and other sleep disorder symptoms among truck drivers and to identify which individual traits and work habits are associated to increased sleepiness and accident risk. We evaluated a sample of 714 truck drivers using a questionnaire (244 face-to-face interviews, 470 self-administered) that included sociodemographic data, personal habits, previous accidents, Epworth Sleepiness Scale (ESS), and the Berlin questionnaire (BQ). Twenty percent of drivers had EDS and 29 % were at high risk for having obstructive sleep apnea syndrome (OSAS). Two hundred sixty-one drivers (36.6 %) reported near-miss accidents (42.5 % sleep related) and 264 (37.0 %), a driving accident (16.3 % sleep related). ESS score ≥ 11 was a risk factor for both near-miss accidents (odds ratio (OR)=3.84, paccidents (OR=2.25, paccidents (OR=3.30, p=0.03). We found an association between high Mallampati score (III-IV) and near misses (OR=1.89, p=0.04). In this sample of Portuguese truck drivers, we observed a high prevalence of EDS and other sleep disorder symptoms. Accident risk was related to sleepiness and antidepressant use. Identifying drivers at risk for OSAS should be a major priority of medical assessment centers, as a public safety policy.

  18. The effects of consecutive night shifts and shift length on cognitive performance and sleepiness: a field study.

    Science.gov (United States)

    Haidarimoghadam, Rashid; Kazemi, Reza; Motamedzadeh, Majid; Golmohamadi, Rostam; Soltanian, Alireza; Zoghipaydar, Mohamad Reza

    2017-06-01

    The aim of this study was to evaluate the effects of consecutive night shifts (CNS) and shift length on cognitive performance and sleepiness. This study evaluated the sleepiness and performance of 30 control room operators (CROs) working in 7 nights, 7 days, 7 days off (7N7D7O) and 30 CROs working in 4 nights, 7 days, 3 nights, 7 days off (4N7D3N7O) shift patterns in a petrochemical complex on the last night shift before swinging into the day shift. To assess cognitive performance, the n-back test, continuous performance test and simple reaction time test were employed. To assess sleepiness, the Karolinska sleepiness scale was used. Both schedules indicated that the correct responses and response times of working memory were reduced (p = 0.001), while intentional errors and sleepiness increased during the shift work (p = 0.001). CNS had a significant impact on reaction time and commission errors (p = 0.001). The main duty of CROs at a petrochemical plant is checking hazardous processes which require appropriate alertness and cognitive performance. As a result, planning for appropriate working hours and suitable number of CNS in a rotating shift system is a contribution to improving CRO performance and enhancing safety.

  19. Sleep habits, insomnia, and daytime sleepiness in a large and healthy community-based sample of New Zealanders.

    Science.gov (United States)

    Wilsmore, Bradley R; Grunstein, Ronald R; Fransen, Marlene; Woodward, Mark; Norton, Robyn; Ameratunga, Shanthi

    2013-06-15

    To determine the relationship between sleep complaints, primary insomnia, excessive daytime sleepiness, and lifestyle factors in a large community-based sample. Cross-sectional study. Blood donor sites in New Zealand. 22,389 individuals aged 16-84 years volunteering to donate blood. N/A. A comprehensive self-administered questionnaire including personal demographics and validated questions assessing sleep disorders (snoring, apnea), sleep complaints (sleep quantity, sleep dissatisfaction), insomnia symptoms, excessive daytime sleepiness, mood, and lifestyle factors such as work patterns, smoking, alcohol, and illicit substance use. Additionally, direct measurements of height and weight were obtained. One in three participants report healthy sample) was associated with insomnia (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.50 to 2.05), depression (OR 2.01, CI 1.74 to 2.32), and sleep disordered breathing (OR 1.92, CI 1.59 to 2.32). Long work hours, alcohol dependence, and rotating work shifts also increase the risk of daytime sleepiness. Even in this relatively young, healthy, non-clinical sample, sleep complaints and primary insomnia with subsequent excess daytime sleepiness were common. There were clear associations between many personal and lifestyle factors-such as depression, long work hours, alcohol dependence, and rotating shift work-and sleep problems or excessive daytime sleepiness.

  20. Caffeine administration at night during extended wakefulness effectively mitigates performance impairment but not subjective assessments of fatigue and sleepiness.

    Science.gov (United States)

    Paech, Gemma M; Banks, Siobhan; Pajcin, Maja; Grant, Crystal; Johnson, Kayla; Kamimori, Gary H; Vedova, Chris B Della

    2016-06-01

    The current study investigated the effects of repeated caffeine administration on performance and subjective reports of sleepiness and fatigue during 50h extended wakefulness. Twenty-four, non-smokers aged 22.5±2.9y (mean±SD) remained awake for two nights (50h) in a controlled laboratory environment. During this period, 200mg of caffeine or placebo gum was administered at 01:00, 03:00, 05:00 and 07:00 on both nights (total of 800mg/night). Neurobehavioral performance and subjective reports were assessed throughout the wake period. Caffeine improved performance compared to placebo, but did not affect overall ratings of subjective sleepiness and fatigue. Performance and sleepiness worsened with increasing time awake for both conditions. However, caffeine slowed performance impairments such that after 50h of wakefulness performance was better following caffeine administration compared to placebo. Caffeine also slowed the increase in subjective sleepiness and performance ratings, but only during the first night of wakefulness. After two nights of sleep deprivation, there was no difference in sleepiness ratings between the two conditions. These results demonstrate that strategic administration of caffeine effectively mitigates performance impairments associated with 50h wakefulness but does not improve overall subjective assessments of sleepiness, fatigue and performance. Results indicate that while performance impairment is alleviated, individuals may continue to report feelings of sleepiness. Individuals who use caffeine as a countermeasure in sustained operations may feel as though caffeine is not effective despite impairments in objective performance being largely mitigated. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1996-01-01

    reporting system on adverse drug reactions. SUBJECTS: A total of 309 critically reviewed cases of drug-induced thrombocytopenia reported during the period from 1968 to the end of 1991. RESULTS: Sodiumaurothiomalate and the combination sulfamethoxazole with trimethoprim were the most commonly reported single...... numerously reported. The still-growing list of thrombocytopenia-inducing agents contained 110 different drugs. At present, 20% of reported cases concern drugs not previously registered as causing thrombocytopenia in Denmark. Twenty-five per cent of all cases were caused by drugs which appeared only...

  2. Prevalence and correlates of poor sleep quality and daytime sleepiness in Belgian truck drivers.

    Science.gov (United States)

    Braeckman, Lutgart; Verpraet, Rini; Van Risseghem, Marleen; Pevernagie, Dirk; De Bacquer, Dirk

    2011-03-01

    Sleepiness and sleep complaints are common among professional drivers. Sleepiness is a considerable problem not only because it affects the drivers' well-being, but also because of the consequences for performance and safety. Assessment of the (self-reported) prevalence and research into the risk factors are thus an important health issue and are also indispensable to prevent productivity loss and work-related accidents and injuries. Therefore, the aim of this study was to describe sleeping, driving, and health characteristics of Belgian truck drivers and to determine occupational and individual factors associated with poor sleep quality and daytime sleepiness. Cross-sectional data were collected using a self-administered questionnaire that included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Berlin Questionnaire (BQ). The mean (SD) age of the 476 studied truck drivers was 42.7 (10.2) yrs and the mean (SD) body mass index was 27.3 (5.1) kg/m(2). Approximately 47% declared that they drove >50 h/wk and found their work schedule unrealistic. The mean (SD) PSQI score was 4.45 (2.7); poor quality of sleep (PSQI >5) was found in 27.2%. The mean (SD) ESS score was 6.79 (4.17); 18% had a score >10. The BQ indicated that 21.5% had a higher risk on obstructive sleep apnea. In multiple logistic regression analysis, low educational level (odds ratio [OR] 1.86), current smoking (OR 1.75), unrealistic work schedule (OR 1.75), and risk for obstructive sleep apnea (OR 2.97) were found to be independent correlates of daytime sleepiness. Poor sleep quality was significantly associated with poor self-perceived health (OR 1.95), unrealistic work schedule (OR 2.85), low job satisfaction (OR 1.91), and less driving experience (OR 1.73). These results show that poor sleep quality and daytime sleepiness were prevalent in Belgian truck drivers. Taking into account that several significant correlates with respect to these sleep problems were identified

  3. Side effects and opioid addiction in radiation-induced mucositis pain control in head and neck cancer

    International Nuclear Information System (INIS)

    Takahashi, Atsuhito; Shoji, Kazuhiko; Mizuta, Masanobu; Morita, Mami; Iki, Takehiro; Kojima, Tsuyoshi

    2011-01-01

    Radiation therapy in head and neck malignancy may trigger mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). Having already reported early opioid efficacy in radiation-induced mucositis pain in head and neck cancer, we discuss whether this resulted in severe side effects and opioid addiction. Of 11 persons (26.2%) with nausea, 3 could not tolerate opioid. Of 33 (78.6%) with constipation, all were controlled by purgatives. Seven had mild sleepiness. None had severe opioid side effects in radiation-induced mucositis pain treatment, but I showed opioid dependence after 128-days opioid administration. While opioid administration in radiation-induced mucositis pain may not cause addiction, lomg-term opioid use should be carefully monitored. (author)

  4. Dissociations among daytime sleepiness, nighttime sleep, and cognitive status in Parkinson's disease.

    Science.gov (United States)

    Goldman, Jennifer G; Ghode, Reena A; Ouyang, Bichun; Bernard, Bryan; Goetz, Christopher G; Stebbins, Glenn T

    2013-09-01

    Daytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits. Ninety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined. The PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures. Daytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Right prefrontal activity reflects the ability to overcome sleepiness during working memory tasks: a functional near-infrared spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Motoyasu Honma

    Full Text Available It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.

  6. Drug Eruptions Induced by Allopurinol Associated with HLA-BFNx015801

    Directory of Open Access Journals (Sweden)

    Meihua Zeng

    2015-01-01

    Full Text Available Allopurinol, a drug commonly used for treating gout and hyperuricemia, is a frequent cause of drug eruptions. Recent investigations suggest that HLA-BFNx015801 allele is a very strong marker for allopurinol-induced cutaneous adverse drug reactions (cADRs. In this article we report two cases of allopurinol-induced drug eruptions in patients carrying the HLA-BFNx015801 allele and review the literature on the association between HLA-BFNx015801 and allopurinol-induced cADRs based on a MEDLINE and PubMed search

  7. Excessive daytime sleepiness in adult patients with ADHD as measured by the Maintenance of Wakefulness Test, an electrophysiologic measure.

    Science.gov (United States)

    Bioulac, Stéphanie; Chaufton, Cyril; Taillard, Jacques; Claret, Astrid; Sagaspe, Patricia; Fabrigoule, Colette; Bouvard, Manuel P; Philip, Pierre

    2015-07-01

    To quantify the objective level of sleepiness in adult attention-deficit/hyperactivity disorder (ADHD) patients and to determine the relationship between excessive daytime sleepiness and simulated driving performance. Forty adult ADHD patients (DSM-IV criteria) and 19 matched healthy control subjects were included between June 30, 2010, and June 19, 2013. All participants completed the Epworth Sleepiness Scale and the Manchester Driving Behavior Questionnaire. After nocturnal polysomnography, they performed 2 neuropsychological tests, a 4 × 40-minute Maintenance of Wakefulness Test, and a 1-hour driving session. The primary outcome measure was the mean sleep latency on the Maintenance of Wakefulness Test. ADHD patients were divided into 3 groups defined by their Maintenance of Wakefulness Test scores. Participants (patients and control subjects) were allocated as follows: sleepy ADHD (0-19 min), intermediate ADHD (20-33 min), alert ADHD (34-40 min), and control group (34-40 min). The driving performance outcome was the mean standard deviation of lateral position of the vehicle during the simulated session. The group mean (SD) Epworth Sleepiness Scale score was higher in ADHD patients (12.1 [4.4]) than in controls (6.0 [2.7]) (P driving performance compared to the other 3 groups (P driving performance. Excessive daytime sleepiness, therefore, may be a key element needed to better evaluate these ADHD patients. ClinicalTrials.gov identifier: NCT01160874. © Copyright 2015 Physicians Postgraduate Press, Inc.

  8. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug......-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments....... In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We...

  9. PTTG1 attenuates drug-induced cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yunguang Tong

    Full Text Available As PTTG1 (pituitary tumor transforming gene abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1(-/- exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1(-/- senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001. p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1(-/- cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1, p53 and p300 to the p21 promoter was enhanced in PTTG1(-/- cells after treatment, suggesting transcriptional regulation of p21. p21 knock down abrogated the observed senescent effects of these drugs, indicating that PTTG1 likely suppresses p21 to regulate drug-induced senescence. PTTG1 also regulated SW620 colon cancer cells response to doxorubicin and TSA mediated by p21. Subcutaneously xenografted PTTG1(-/- HCT116 cells developed smaller tumors and exhibited enhanced responses to doxorubicin. PTTG1(-/- tumor tissue derived from excised tumors exhibited increased doxorubicin-induced senescence. As senescence is a determinant of cell responses to anti-neoplastic treatments, these findings suggest PTTG1 as a tumor cell marker to predict anti-neoplastic treatment outcomes.

  10. Drug-induced low blood sugar

    Science.gov (United States)

    Drug-induced low blood sugar is low blood glucose that results from taking medicine. ... Low blood sugar (hypoglycemia) is common in people with diabetes who are taking insulin or other medicines to control their diabetes. ...

  11. Frequency of Burnout, Sleepiness and Depression in Emergency Medicine Residents with Medical Errors in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Alireza Aala

    2014-07-01

    Full Text Available Aims: Medical error is a great concern of the patients and physicians. It usually occurs due to physicians’ exhaustion, distress and fatigue. In this study, we aimed to evaluate frequency of distress and fatigue among emergency medicine residents reporting a medical error. Materials and Methods: The study population consisted of emergency medicine residents who completed an emailed questionnaire including self-assessment of medical errors, the Epworth Sleepiness Scale (ESS score, the Maslach Burnout Inventory, and PRIME-MD validated depression screening tool.   Results: In this survey, 100 medical errors were reported including diagnostic errors in 53, therapeutic errors in 24 and following errors in 23 subjects. Most errors were reported by males and third year residents. Residents had no signs of depression, but all had some degrees of sleepiness and burnout. There were significant differences between errors subtypes and age, residency year, depression, sleepiness and burnout scores (p<0.0001.   Conclusion: In conclusion, residents committing a medical error usually experience burnout and have some grades of sleepiness that makes them less motivated increasing the probability of medical errors. However, as none of the residents had depression, it could be concluded that depression has no significant role in medical error occurrence and perhaps it is a possible consequence of medical error.    Keywords: Residents; Medical error; Burnout; Sleepiness; Depression

  12. Prediction of Cognitive Performance and Subjective Sleepiness Using a Model of Arousal Dynamics.

    Science.gov (United States)

    Postnova, Svetlana; Lockley, Steven W; Robinson, Peter A

    2018-04-01

    A model of arousal dynamics is applied to predict objective performance and subjective sleepiness measures, including lapses and reaction time on a visual Performance Vigilance Test (vPVT), performance on a mathematical addition task (ADD), and the Karolinska Sleepiness Scale (KSS). The arousal dynamics model is comprised of a physiologically based flip-flop switch between the wake- and sleep-active neuronal populations and a dynamic circadian oscillator, thus allowing prediction of sleep propensity. Published group-level experimental constant routine (CR) and forced desynchrony (FD) data are used to calibrate the model to predict performance and sleepiness. Only the studies using dim light (performance measures during CR and FD protocols, with sleep-wake cycles ranging from 20 to 42.85 h and a 2:1 wake-to-sleep ratio. New metrics relating model outputs to performance and sleepiness data are developed and tested against group average outcomes from 7 (vPVT lapses), 5 (ADD), and 8 (KSS) experimental protocols, showing good quantitative and qualitative agreement with the data (root mean squared error of 0.38, 0.19, and 0.35, respectively). The weights of the homeostatic and circadian effects are found to be different between the measures, with KSS having stronger homeostatic influence compared with the objective measures of performance. Using FD data in addition to CR data allows us to challenge the model in conditions of both acute sleep deprivation and structured circadian misalignment, ensuring that the role of the circadian and homeostatic drives in performance is properly captured.

  13. Assessment of sleepiness, fatigue, and depression among Gulf Cooperation Council commercial airline pilots.

    Science.gov (United States)

    Aljurf, Tareq M; Olaish, Awad H; BaHammam, Ahmed S

    2018-05-01

    No studies have assessed the prevalence of fatigue, depression, sleepiness, and the risk of obstructive sleep apnea (OSA) among commercial airlines pilots in the Gulf Cooperation Council (GCC). This was a quantitative cross-sectional study conducted among pilots who were on active duty and had flown during the past 6 months for one of three commercial airline companies. We included participants with age between 20 and 65 years. Data were collected using a predesigned electronic questionnaire composed of questions related to demographic information in addition to the Fatigue Severity Scale (FSS), the Berlin Questionnaire, the Epworth Sleepiness Scale (ESS), and the Hospital Anxiety and Depression Scale (HADS). The study included 328 pilots with a mean age ± standard deviation of 41.4 ± 9.7 years. Overall, 224 (68.3%) pilots had an FSS score ≥ 36 indicating severe fatigue and 221 (67.4%) reported making mistakes in the cockpit because of fatigue. One hundred and twelve (34.1%) pilots had an ESS score ≥ 10 indicating excessive daytime sleepiness and 148 (45.1%) reported falling asleep at the controls at least once without previously agreeing with their colleagues. One hundred and thirteen (34.5%) pilots had an abnormal HADS depression score (≥ 8), and 96 (29.3%) pilots were at high risk for OSA requiring further assessment. Fatigue, sleepiness, risk of OSA, and depression are prevalent among GCC commercial airline pilots. Regular assessment by aviation authorities is needed to detect and treat these medical problems.

  14. The prevalence of excessive daytime sleepiness among academic physicians and its impact on the quality of life and occupational performance

    Directory of Open Access Journals (Sweden)

    Aclan Ozder

    2015-08-01

    Full Text Available Objectives: Sleep disorders can affect health and occupational performance of physicians as well as outcomes in patients. The purpose of this study was to assess the prevalence of excessive daytime sleepiness (EDS measured by the Epworth Sleepiness Scale (ESS among academic physicians at a tertiary academic medical center in an urban area in the northwest region of Turkey, and to establish a relationship between the self-perceived sleepiness and the quality of life using the EuroQol-5 dimensions (EQ-5D. Material and Methods: A questionnaire prepared by the researchers after scanning the literature on the subject was e-mailed to the academic physicians of a tertiary academic medical center in Istanbul. The ESS and the EQ-5D were also included in the survey. The e-mail database of the institution directory was used to compile a list of active academic physicians who practiced clinical medicine. Paired and independent t tests were used for the data analysis at a significance level of p 10 (p < 0.001. In the case of the EQ-5D index and visual analogue scale of the EQ-5D questionnaire (EQ-5D VAS, the status of sleepiness of academic physicians was associated with a poorer quality of life (p < 0.001. Conclusions: More than a 1/4 of the academic physicians suffered from sleepiness. There was an association between the poor quality of life and daytime sleepiness. There was also a positive relationship between habitual napping and being sleepy during the day.

  15. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Directory of Open Access Journals (Sweden)

    Anna K Jönsson

    2017-07-01

    Full Text Available Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA. Methods: All individual adverse drug reactions (ADR reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72. Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia

  16. Job demands and resting and napping opportunities for nurses during night shifts: impact on sleepiness and self-evaluated quality of healthcare.

    Science.gov (United States)

    Barthe, Béatrice; Tirilly, Ghislaine; Gentil, Catherine; Toupin, Cathy

    2016-01-01

    The aim of this field study is to describe night shift resting and napping strategies and to examine their beneficial effects on sleepiness and quality of work. The study was carried out with 16 nurses working in an intensive care unit. Data collected during 20 night shifts were related to job demands (systematic observations), to the duration and timing of rests and naps taken by nurses (systematic observations, sleep diaries), to sleepiness (Karolinska Sleepiness Scale), and to quality of work scores (visual analog scale). The results showed that the number of rests and naps depended on the job demands. Resting and napping lowered the levels of sleepiness at the end of the shift. There was no direct relationship between sleepiness and the quality of work score. Discussions about the choice of indicators for the quality of work are necessary. Suggestions for implementing regulations for prescribed napping during night shifts are presented.

  17. Nintendo Wii Fit-Based Sleepiness Testing is Not Impaired by Contagious Sleepiness.

    Science.gov (United States)

    Tietäväinen, Aino; Kuvaldina, Maria; Hæggström, Edward

    2018-06-01

    Sleep deprivation may cause accidents, and it has deteriorating effects on health. A measurement of postural steadiness by a portable and affordable Nintendo Wii Fit balance board can be used to quantify a person's alertness. At work, people are under the influence of their environment-often other people-that may affect their alertness. This work investigates whether sleep deprivation among people is "contagious," as quantified by sway measures. We measured 21 volunteers' postural steadiness while alert and sleep deprived. During the measurements, a screen placed in front of the participants showed a footage of either alert or sleep-deprived faces. We found a significant difference between the day time and night time steadiness, but found no effect resulting from watching footage of sleep-deprived people. This finding shows that a posturographic sleepiness tester quantifies physiological sleep deprivation, and is insensitive to the influence of social factors.

  18. Drug: D00785 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available .gif ... Neuropsychiatric agent ... DG01568 ... MAO inhibitor ... DG01512 ... Monoamine oxidase B inhibitor ... DG01967 ... Antiparkinson...169 ATC code: N04BD01 Chemical group: DG00864 ... Antiparkinsonian in combination w

  19. Sleep and sleepiness during an ultra long-range flight operation between the Middle East and United States.

    Science.gov (United States)

    Holmes, Alexandra; Al-Bayat, Soha; Hilditch, Cassie; Bourgeois-Bougrine, Samira

    2012-03-01

    This study provides a practical example of fatigue risk management in aviation. The sleep and sleepiness of 44 pilots (11 trips × 4 pilot crew) working an ultra long-range (ULR; flight time >16 h) round-trip operation between Doha and Houston was assessed. Sleep was assessed using activity monitors and self-reported sleep diaries. Mean Karolinska Sleepiness Scores (KSS) for climb and descent did not exceed 5 ("neither alert nor sleepy"). Mean daily sleep duration was maintained above 6.3h throughout the operation. During in-flight rest periods, 98% of pilots obtained sleep and sleepiness was subsequently reduced. On layover (49.5h) crew were advised to sleep on Doha or Universal Co-ordinated Time (UTC), but 64% slept during the local (social) night time. Pilots originating from regions with a siesta culture were more likely to nap and made particularly effective use of their daytime in-flight rest periods. The results indicate that the operation is well designed from a fatigue management perspective. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Association between reported sleep need and sleepiness at the wheel: comparative study on French highways between 1996 and 2011.

    Science.gov (United States)

    Quera-Salva, M A; Hartley, S; Sauvagnac-Quera, R; Sagaspe, P; Taillard, J; Contrand, B; Micoulaud, J A; Lagarde, E; Barbot, F; Philip, P

    2016-12-21

    To investigate the evolution over 15 years of sleep schedules, sleepiness at the wheel and driving risk among highway drivers. Comparative survey including questions on usual sleep schedules and before the trip, sleepiness at the wheel, the Epworth sleepiness scale, Basic Nordic Sleep Questionnaire (BNSQ) and a travel questionnaire. 80% of drivers stopped by the highway patrol agreed to participate in both studies with a total of 3545 drivers in 2011 and 2196 drivers in 1996 interviewed. After standardisation based on sex, age and mean annual driving distance, drivers in 2011 reported shorter sleep time on week days (psleep time (p15 indicating severe sleepiness. Even if drivers in 2011 reported good sleep hygiene prior to a highway journey, drivers have reduced their mean weekly sleep duration over 15 years and have a higher risk of sleepiness at the wheel. Sleep hygiene for automobile drivers remains an important concept to address. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Clinical implications of daytime sleepiness for the academic performance of middle school-aged adolescents with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Langberg, Joshua M; Dvorsky, Melissa R; Marshall, Stephen; Evans, Steven W

    2013-10-01

    This study investigated the relative impact of total time slept per night and daytime sleepiness on the academic functioning of 100 middle school-aged youth (mean age = 11.9) with attention deficit hyperactivity disorder (ADHD). The primary goal of the study was to determine if total time slept per night and/or daytime sleepiness, as measured by youth self-report on the Pediatric Daytime Sleepiness Scale (PDSS), predicted academic functioning above and beyond symptoms of ADHD and relevant covariates, such as intelligence, achievement scores and parent education level. Self-reported daytime sleepiness but not self-reported total time slept per night was associated significantly with all academic outcomes. When examined in a hierarchical regression model, self-reported daytime sleepiness significantly predicted parent-rated homework problems and academic impairment and teacher-rated academic competence above and beyond symptoms of ADHD and relevant covariates, but did not predict grade point average or teacher-rated academic impairment. The implications of these findings for understanding more clearly the association between ADHD and sleep and the functional implications of this relationship are discussed. © 2013 European Sleep Research Society.

  2. In silico modeling to predict drug-induced phospholipidosis

    International Nuclear Information System (INIS)

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G.; Sadrieh, Nakissa

    2013-01-01

    Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure–activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80–81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ≥ 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. - Highlights: • New in silico models for predicting drug-induced phospholipidosis (DIPL) are described. • The training set data in the models is derived from the FDA's phospholipidosis database. • We find excellent predictivity values of the models based on external validation. • The models can support drug screening and regulatory decision-making on DIPL

  3. Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2008-01-01

    Full Text Available The conditioned place preference (CPP model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

  4. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Directory of Open Access Journals (Sweden)

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

  5. Fatigued on Venus, sleepy on Mars-gender and racial differences in symptoms of sleep apnea.

    Science.gov (United States)

    Eliasson, Arn H; Kashani, Mariam D; Howard, Robin S; Vernalis, Marina N; Modlin, Randolph E

    2015-03-01

    Clinical guidelines for the care of obstructive sleep apnea (OSA) recommend evaluation of daytime sleepiness but do not specify evaluation of fatigue. We studied how subjects with and without OSA experience fatigue and sleepiness, examining the role of gender and race. Consecutive subjects entering our heart health registry completed validated questionnaires including Berlin Questionnaire for OSA, Fatigue Scale, and Epworth Sleepiness Scale. Data analysis was performed only with Whites and Blacks as there were too few subjects of other races for comparison. Of 384 consecutive subjects, including 218 women (57 %), there were 230 Whites (60 %) and 154 Blacks (40 %), with average age of 55.9 ± 12.8 years. Berlin Questionnaires identified 221 subjects (58 %) as having high likelihood for OSA. Fatigue was much more common in women (75 %) than in men (46 %) with OSA (p men (29 %) without OSA (p = 0.86). In multivariate analysis, men with OSA were sleepier than women; Black men with OSA had higher Epworth scores (mean ± SD, 12.8 ± 5.2) compared to White men (10.6 ± 5.3), White women (10.0 ± 4.5), and Black women (10.5 ± 5.2), p = 0.05. These gender differences were not related to the effects of age, body mass index, perceived stress, sleep duration, or thyroid function. Women report fatigue more commonly with OSA than men. Men experience sleepiness more commonly with OSA than women. The findings suggest that evaluation of sleep disorders must include an assessment of fatigue in addition to sleepiness to capture the experience of women.

  6. Idiosyncratic Drug-Induced Liver Injury: Is Drug-Cytokine Interaction the Linchpin?

    Science.gov (United States)

    Roth, Robert A; Maiuri, Ashley R; Ganey, Patricia E

    2017-02-01

    Idiosyncratic drug-induced liver injury continues to be a human health problem in part because drugs that cause these reactions are not identified in current preclinical testing and because progress in prevention is hampered by incomplete knowledge of mechanisms that underlie these adverse responses. Several hypotheses involving adaptive immune responses, inflammatory stress, inability to adapt to stress, and multiple, concurrent factors have been proposed. Yet much remains unknown about how drugs interact with the liver to effect death of hepatocytes. Evidence supporting hypotheses implicating adaptive or innate immune responses in afflicted patients has begun to emerge and is bolstered by results obtained in experimental animal models and in vitro systems. A commonality in adaptive and innate immunity is the production of cytokines, including interferon-γ (IFNγ). IFNγ initiates cell signaling pathways that culminate in cell death or inhibition of proliferative repair. Tumor necrosis factor-α, another cytokine prominent in immune responses, can also promote cell death. Furthermore, tumor necrosis factor-α interacts with IFNγ, leading to enhanced cellular responses to each cytokine. In this short review, we propose that the interaction of drugs with these cytokines contributes to idiosyncratic drug-induced liver injury, and mechanisms by which this could occur are discussed. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  7. In-car countermeasures open window and music revisited on the real road: popular but hardly effective against driver sleepiness

    NARCIS (Netherlands)

    Schwarz, J.F.A.; Ingre, M.; Fors, C.; Anund, A.; Kecklund, L.G.; Taillard, J.; Philip, P.; Äkerstedt, T.

    2012-01-01

    This study investigated the effects of two very commonly used countermeasures against driver sleepiness, opening the window and listening to music, on subjective and physiological sleepiness measures during real road driving. In total, 24 individuals participated in the study. Sixteen participants

  8. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

    2007-01-01

    In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...... in focal ischemia by pharmacological alteration of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle...... that the core body temperature was reduced by 1.7 degrees C for 24 hours after MCAO in rats treated with Talipexole. This treatment induced a significant reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that the reduction in infarct volume is related to drug-induced hypothermia...

  9. The discovery of drug-induced illness.

    Science.gov (United States)

    Jick, H

    1977-03-03

    The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users.

  10. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

    Science.gov (United States)

    Nogawa, Hisashi; Kawai, Tomoyuki

    2014-10-15

    Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Sleep length and quality, sleepiness and urinary melatonin among healthy Danish nurses with shift work during work and leisure time

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Hansen, Åse Marie; Hansen, Johnni

    2009-01-01

    Sleep problems are common effects of shift work. The aim of the present study was to evaluate how different types of shift affect sleep and sleepiness, and to relate sleepiness to urinary 6-sulfatoxymelatonin....

  12. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  13. Up-regulation of hypoxia-inducible factor (HIF)-1α and HIF-target genes in cortical neurons by the novel multifunctional iron chelator anti-Alzheimer drug, M30.

    Science.gov (United States)

    Avramovich-Tirosh, Y; Bar-Am, O; Amit, T; Youdim, M B H; Weinreb, O

    2010-06-01

    Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelator, M30, possessing the neuroprotective propargylamine moiety of the anti-Parkinsonian drug, rasagiline (Azilect) and antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of our iron chelator, VK28. M30 was recently found to confer potential neuroprotective effects in vitro and in various preclinical neurodegenerative models and regulate the levels and processing of the Alzheimer's amyloid precursor protein and its toxic amyloidogenic derivative, Abeta. Here, we show that M30 activates the hypoxia-inducible factor (HIF)-1alpha signaling pathway, thus promoting HIF-1alpha mRNA and protein expression levels, as well as increasing transcription of HIF-1alpha-dependent genes, including vascular endothelial growth factor, erythropoietin, enolase-1, p21 and tyrosine hydroxylase in rat primary cortical cells. In addition, M30 also increased the expression levels of the transcripts of brain derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43). Regarding aspects of relevance to Alzheimer's disease (AD), western blotting analysis of glycogen synthase kinase- 3beta (GSK-3beta) signaling pathway revealed that M30 enhanced the levels of phospho-AKT (Ser473) and phospho- GSK-3beta (Ser9) and attenuated Tau phosphorylation. M30 was also shown to protect cultured cortical neurons against Abeta(25-35) toxicity. All these multimodal pharmacological activities of M30 might be beneficial for its potent efficacy in the prevention and treatment of neurodegenerative conditions, such as Parkinson's disease and AD in which oxidative stress and iron-mediated toxicity are involved.

  14. Snoring, sleep quality, and sleepiness across attention-deficit/hyperactivity disorder subtypes.

    Science.gov (United States)

    LeBourgeois, Monique K; Avis, Kristin; Mixon, Michele; Olmi, Joe; Harsh, John

    2004-05-01

    To characterize the relationship between pediatric attention-deficit/hyperactivity disorder (ADHD) subtypes, chronic snoring, and indexes of sleep quality and daytime sleepiness. A cross-sectional design with planned comparisons of ADHD (all subtypes) versus general community controls; ADHD Predominantly Inattentive Type (ADHD-I) versus a group with both ADHD Predominantly Hyperactive/Impulsive Type (ADHD-HI) and ADHD Combined Type (ADHD-C); and ADHD-HI versus ADHD-C. Subjects recruited from a pediatric clinic, a university psycholgy clinic, and the general community. Caretakers of 74 children (45 with ADHD, 29 community controls; 53 boys, 21 girls; mean age, 9.6 years; age range, 6 to 16 years). Thirty-two (71.1%) of the children with ADHD were taking stimulant medication and 7 (15.5%) were taking hypnotic medication. N/A. Caretakers completed the Pediatric Sleep Questionnaire (PSQ) and the Children's Sleep-Wake Scale (CSWS). Only the ADHD-HI diagnosis was associated with an increased likelihood of chronic snoring. Sleep quality was poorer among children with ADHD than controls; however, there were no differences in sleep quality across ADHD subtypes. Sleepiness was greater in children with ADHD, especially the ADHD-I Type. Chronic snoring may be a correlated feature in only a subgroup of the ADHD population, possibly those more likely to be diagnosed with ADHD-HI. Although children with ADHD have poorer sleep quality and greater daytime sleepiness, these 2 features of ADHD are not closely related.

  15. Combined electrocardiogram and photoplethysmogram measurements as an indicator of objective sleepiness

    International Nuclear Information System (INIS)

    Chua, Chern-Pin; McDarby, Gary; Heneghan, Conor

    2008-01-01

    There is considerable interest in unobtrusive and portable methods of monitoring sleepiness outside the laboratory setting. This study evaluates the usefulness of combined electrocardiogram (ECG) and photoplethysmogram (PPG) measurements for estimating psychomotor vigilance. The psychomotor vigilance test (PVT) was performed at various points over the course of a day, and one channel each of ECG and PPG was recorded simultaneously. Features derived from ECG and PPG were entered into multiple linear regression models to estimate PVT values. A double-loop, subject-independent validation scheme was used to develop and validate the models. We show that features obtained from the RR interval were reasonably useful for estimating absolute PVT levels, but were somewhat inadequate for estimating within-subject PVT changes. Combined ECG and PPG measurements appear to be useful for predicting PVT values, and deserve further investigation for portable sleepiness monitoring

  16. Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

    Directory of Open Access Journals (Sweden)

    Pinaki Chakravarty

    2016-01-01

    Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

  17. Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli.

    Science.gov (United States)

    Taher, Yousef A; Samud, Awatef M; Ratimy, Aya H; Seabe, Areeje M

    2012-01-01

    The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits. The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05%) and 22 males (10.95%), were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS) was used for the assessment of daytime sleepiness. This study showed that the total sleep time (TST) on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of >10. Furthermore, our results showed that the majority of students (>92%) reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleep-wake schedule. These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.

  18. Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli

    Directory of Open Access Journals (Sweden)

    Yousef A. Taher

    2012-10-01

    Full Text Available Background: The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits. Aim: The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes. Methods: A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05% and 22 males (10.95%, were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS was used for the assessment of daytime sleepiness. Results: This study showed that the total sleep time (TST on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of >10. Furthermore, our results showed that the majority of students (>92% reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleep–wake schedule. Conclusion: These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.

  19. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999

    DEFF Research Database (Denmark)

    Andersen, V; Sonne, J; Andersen, M

    2001-01-01

    valproate (two cases), clomipramine (one case) and azathioprine (one case). Definite relationship was stated for mesalazine (three cases), azathioprine (two cases) and simvastatin (one case) on the basis of re-challenge. A possible or probable causality was considered for a further 30 drugs including 5...... (measles" mumps/rubella) vaccination. CONCLUSION: Drug-induced pancreatitis is rarely reported. The incidence may be increasing and the course is often serious. This is the first report on definite simvastatin-induced pancreatitis. Further studies on the pancreotoxic potential of drugs are warranted.......OBJECTIVES: To present an update on drug-induced pancreatitis reported to the Danish Committee on Adverse Drug Reactions. DESIGN: Retrospective study of spontaneous case reports to the Danish reporting system on adverse drug reactions. METHODS: All cases of suspected drug-induced pancreatitis...

  20. Children's Sleep, Sleepiness, and Performance on Cognitive Tasks

    OpenAIRE

    Buckhalt, Joseph A.

    2011-01-01

    While causal connections between sleep deprivation and attention, learning, and memory have been well established in adults, much less research has been done with children. Relations between the amount and quality of sleep and daytime sleepiness have been found for a number of cognitive and academic tasks in several groups of children. These relations have been found for children who have sleep disorders, for children with disorders involving cognitive impairment, and for typically developing...

  1. Excessive Daytime Sleepiness is Associated with Longer Culprit Lesion and Adverse Outcomes in Patients with Coronary Artery Disease

    Science.gov (United States)

    Lee, Chi-Hang; Ng, Wai-Yee; Hau, William; Ho, Hee-Hwa; Tai, Bee-Choo; Chan, Mark Y.; Richards, A. Mark; Tan, Huay-Cheem

    2013-01-01

    Study Objectives: We assessed whether excessive daytime sleepiness was associated with coronary plaque phenotype and subsequent adverse cardiovascular events. Methods: Prospective cohort study. Intravascular ultrasound (IVUS) examination of the culprit coronary stenosis was performed. The Epworth Sleepiness Scale (ESS) questionnaire was administered, and the patients were divided into 2 groups—(1) sleepier and (2) less sleepy—based on the ESS score. Adverse cardiovascular outcomes were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure admission. Results: One hundred seventeen patients undergoing urgent or non-urgent coronary angiography were recruited. Compared with the less sleepy group (ESS ≤ 10, n = 87), the sleepier group (ESS > 10, n = 30) had higher serum levels of total cholesterol and of low-density-lipoprotein cholesterols (p 10 was associated with longer culprit lesions and future adverse cardiovascular events. Citation: Lee CH; Ng WY; Hau W; Ho HH; Tai BC; Chan MY; Richards AM; Tan HC. Excessive daytime sleepiness is associated with longer culprit lesion and adverse outcomes in patients with coronary artery disease. J Clin Sleep Med 2013;9(12):1267-1272. PMID:24340288

  2. Prevalence of sleepiness while driving four-wheel motor vehicles in Fiji: a population-based survey (TRIP 9).

    Science.gov (United States)

    Herman, Josephine; Ameratunga, Shanthi N; Wainiqolo, Iris; Kafoa, Berlin; Robinson, Elizabeth; McCaig, Eddie; Jackson, Rod

    2013-08-01

    Sleepiness has been shown to be a risk factor for road crashes in high-income countries, but has received little attention in low- and middle-income countries. We examined the prevalence of sleepiness and sleep-related disorders among drivers of four-wheel motor vehicles in Fiji. Using a two-stage cluster sampling roadside survey conducted over 12 months, we recruited a representative sample of people driving four-wheel motor vehicles on the island of Viti Levu, Fiji. A structured interviewer-administered questionnaire sought self-report information on driver characteristics including sleep-related measures. The 752 motor vehicle drivers recruited (84% response rate) were aged 17-75 years, with most driving in Viti Levu undertaken by male subjects (93%), and those identifying with Indian (70%) and Fijian (22%) ethnic groups. Drivers who reported that they were not fully alert accounted for 17% of driving, while a further 1% of driving was undertaken by those who reported having difficulty staying awake or feeling sleepy. A quarter of the driving time among 15-24-year-olds included driving while sleepy or not fully alert, with a similar proportion driving while chronically sleep deprived (ie, with less than five nights of adequate sleep in the previous week=27%). Driving while acutely or chronically sleep deprived was generally more common among Fijians compared with Indians. Driving while not fully alert is relatively common in Fiji. Sleepiness while driving may be an important contributor to road traffic injuries in this and other low- and middle-income countries.

  3. Associations of excessive sleepiness on duty with sleeping hours and number of days of overnight work among medical residents in Japan.

    Science.gov (United States)

    Wada, Koji; Sakata, Yumi; Theriault, Gilles; Narai, Rie; Yoshino, Yae; Tanaka, Katsutoshi; Aizawa, Yoshiharu

    2007-11-01

    Despite long-standing concerns regarding the effects of working hours on the performance and health of medical residents, and the patients' safety, prior studies have not shown an association of excessive sleepiness with the number of sleeping hours and days of overnight work among medical residents. In August 2005, a questionnaire was mailed to 227 eligible participants at 16 teaching hospitals. The total number of sleeping hours in the last 30 d was estimated from the average number of sleeping hours during regular days and during days with overnight work, and the number of days of overnight work. Multiple logistic regression analysis was used to adjust for potentially associated variables. A total of 149 men and 47 women participated in this study. The participation rate was 86.3%. Among the participants, 55 (28.1%) suffered from excessive sleepiness. Excessive sleepiness was associated with sleeping for less than 150 h in the last 30 d (corrected odds ratio [cOR]=1.57; 95% confidence interval [CI], 1.02-2.16). The number of days of overnight work in the last 30 d showed no association with excessive sleepiness. Excessive sleepiness was also associated with smoking (cOR, 1.65; 95%CI, 1.01-2.32). Medical residents who slept for less than 150 h in the last 30 d and smoked had a significantly higher risk of excessive sleepiness on duty.

  4. Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

    Science.gov (United States)

    Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

    2013-01-01

    Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD

  5. Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury.

    Science.gov (United States)

    Weaver, Richard J; Betts, Catherine; Blomme, Eric A G; Gerets, Helga H J; Gjervig Jensen, Klaus; Hewitt, Philip G; Juhila, Satu; Labbe, Gilles; Liguori, Michael J; Mesens, Natalie; Ogese, Monday O; Persson, Mikael; Snoeys, Jan; Stevens, James L; Walker, Tracy; Park, B Kevin

    2017-07-01

    The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered: The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities. Opportunities for research efforts in areas necessitating the development of specific tests and improved mechanistic understanding are highlighted. Expert Opinion: Use of in vitro test systems for safety optimization will remain a core activity in drug discovery. Substantial inroads have been made with a number of assays established for human Drug-induced Liver Injury. There nevertheless remain significant gaps with a need for improved in vitro tools and novel tests to address specific mechanisms of human Drug-Induced Liver Injury. Progress in these areas will necessitate not only models fit for application, but also mechanistic understanding of how chemical insult on the liver occurs in order to identify translational and quantifiable readouts for decision-making.

  6. Driver sleepiness and risk of motor vehicle crash injuries: a population-based case control study in Fiji (TRIP 12).

    Science.gov (United States)

    Herman, Josephine; Kafoa, Berlin; Wainiqolo, Iris; Robinson, Elizabeth; McCaig, Eddie; Connor, Jennie; Jackson, Rod; Ameratunga, Shanthi

    2014-03-01

    Published studies investigating the role of driver sleepiness in road crashes in low and middle-income countries have largely focused on heavy vehicles. We investigated the contribution of driver sleepiness to four-wheel motor vehicle crashes in Fiji, a middle-income Pacific Island country. The population-based case control study included 131 motor vehicles involved in crashes where at least one person died or was hospitalised (cases) and 752 motor vehicles identified in roadside surveys (controls). An interviewer-administered questionnaire completed by drivers or proxies collected information on potential risks for crashes including sleepiness while driving, and factors that may influence the quantity or quality of sleep. Following adjustment for confounders, there was an almost six-fold increase in the odds of injury-involved crashes for vehicles driven by people who were not fully alert or sleepy (OR 5.7, 95%CI: 2.7, 12.3), or those who reported less than 6 h of sleep during the previous 24 h (OR 5.9, 95%CI: 1.7, 20.9). The population attributable risk for crashes associated with driving while not fully alert or sleepy was 34%, and driving after less than 6 h sleep in the previous 24 h was 9%. Driving by people reporting symptoms suggestive of obstructive sleep apnoea was not significantly associated with crash risk. Driver sleepiness is an important contributor to injury-involved four-wheel motor vehicle crashes in Fiji, highlighting the need for evidence-based strategies to address this poorly characterised risk factor for car crashes in less resourced settings. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Excessive daytime sleepiness and subsequent development of Parkinson disease.

    Science.gov (United States)

    Abbott, R D; Ross, G W; White, L R; Tanner, C M; Masaki, K H; Nelson, J S; Curb, J D; Petrovitch, H

    2005-11-08

    To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD). EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001. During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

  8. Ocular Measures of Sleepiness Are Increased in Night Shift Workers Undergoing a Simulated Night Shift Near the Peak Time of the 6-Sulfatoxymelatonin Rhythm

    Science.gov (United States)

    Ftouni, Suzanne; Sletten, Tracey L.; Nicholas, Christian L.; Kennaway, David J.; Lockley, Steven W.; Rajaratnam, Shantha M.W.

    2015-01-01

    Study Objectives: The study examined the relationship between the circadian rhythm of 6-sulphatoxymelatonin (aMT6s) and ocular measures of sleepiness and neurobehavioral performance in shift workers undergoing a simulated night shift. Methods: Twenty-two shift workers (mean age 33.4, SD 11.8 years) were tested at approximately the beginning (20:00) and the end (05:55) of a simulated night shift in the laboratory. At the time point corresponding to the end of the simulated shift, 14 participants were classified as being within range of 6-sulphatoxymelatonin (aMT6s) acrophase— defined as 3 hours before or after aMT6s peak—and 8 were classified as outside aMT6s acrophase range. Participants completed the Karolinska Sleepiness Scale (KSS) and the auditory psychomotor vigilance task (aPVT). Waking electroencephalography (EEG) was recorded and infrared reflectance oculography was used to collect ocular measures of sleepiness: positive and negative amplitude/velocity ratio (PosAVR, NegAVR), mean blink total duration (BTD), the percentage of eye closure (%TEC), and a composite score of sleepiness levels (Johns Drowsiness Scale; JDS). Results: Participants who were tested within aMT6s acrophase range displayed higher levels of sleepiness on ocular measures (%TEC, BTD, PosAVR, JDS), objective sleepiness (EEG delta power frequency band), subjective ratings of sleepiness, and neurobehavioral performance, compared to those who were outside aMT6s acrophase range. Conclusions: The study demonstrated that objective ocular measures of sleepiness are sensitive to circadian rhythm misalignment in shift workers. Citation: Ftouni S, Sletten TL, Nicholas CL, Kennaway DJ, Lockley SW, Rajaratnam SM. Ocular measures of sleepiness are increased in night shift workers undergoing a simulated night shift near the peak time of the 6-sulfatoxymelatonin rhythm. J Clin Sleep Med 2015;11(10):1131–1141. PMID:26094925

  9. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    Directory of Open Access Journals (Sweden)

    Liane Rabinowich

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

  10. Glucose hypermetabolism in the thalamus of patients with drug-induced blepharospasm.

    Science.gov (United States)

    Suzuki, Y; Kiyosawa, M; Wakakura, M; Mochizuki, M; Ishiwata, K; Oda, K; Ishii, K

    2014-03-28

    We examined the difference in cerebral function alterations between drug-induced blepharospasm patients and essential blepharospasm (EB) patients by using positron emission tomography with (18)F-fluorodeoxyglucose. Cerebral glucose metabolism was examined in 21 patients with drug-induced blepharospasm (5 men and 16 women; mean age, 53.1 [range, 29-78] years), 21 essential EB patients (5 men and 16 women; mean age, 53.0 [range, 33-72] years) and 24 healthy subjects (6 men and 18 women; mean age, 57.9 [range, 22-78] years) with long-term history of benzodiazepines use (drug healthy subjects). Drug-induced blepharospasm patients developed symptoms while taking benzodiazepines or thienodiazepines. Sixty-three normal volunteers (15 men and 48 women; mean age, 53.6 [range, 20-70] years) were examined as controls. Differences between the patient groups and control group were examined by statistical parametric mapping. Additionally, we defined regions of interests on both sides of the thalamus, caudate nucleus, anterior putamen, posterior putamen and primary somatosensory area. The differences between groups were tested using two-sample t-tests with Bonferroni correction for multiple comparisons. Cerebral glucose hypermetabolism on both side of the thalamus was detected in drug-induced blepharospasm, EB patients and drug healthy subjects by statistical parametric mapping. In the analysis of regions of interest, glucose metabolism in both sides of the thalamus in the drug-induced blepharospasm group was significantly lower than that in the EB group. Moreover, we observed glucose hypermetabolism in the anterior and posterior putamen bilaterally in EB group but not in drug-induced blepharospasm group and drug healthy subjects. Long-term regimens of benzodiazepines or thienodiazepines may cause down-regulation of benzodiazepine receptors in the brain. We suggest that the functional brain alteration in drug-induced blepharospasm patients is similar to that in EB patients, and

  11. An Overview on the Proposed Mechanisms of Antithyroid Drugs-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2015-03-01

    Full Text Available Drug-induced liver injury (DILI is a major problem for pharmaceutical industry and drug development. Mechanisms of DILI are many and varied. Elucidating the mechanisms of DILI will allow clinicians to prevent liver failure, need for liver transplantation, and death induced by drugs. Methimazole and propylthiouracil (PTU are two convenient antithyroid agents which their administration is accompanied by hepatotoxicity as a deleterious side effect. Although several cases of antithyroid drugs-induced liver injury are reported, there is no clear idea about the mechanism(s of hepatotoxicity induced by these medications. Different mechanisms such as reactive metabolites formation, oxidative stress induction, intracellular targets dysfunction, and immune-mediated toxicity are postulated to be involved in antithyroid agents-induced hepatic damage. Due to the idiosyncratic nature of antithyroid drugs-induced hepatotoxicity, it is impossible to draw a specific conclusion about the mechanisms of liver injury. However, it seems that reactive metabolite formation and immune-mediated toxicity have a great role in antithyroids liver toxicity, especially those caused by methimazole. This review attempted to discuss different mechanisms proposed to be involved in the hepatic injury induced by antithyroid drugs.

  12. Associations of Caffeinated Beverage Consumption and Screen Time with Excessive Daytime Sleepiness in Korean High School Students

    OpenAIRE

    Jun, Nuri; Lee, Aeri; Baik, Inkyung

    2017-01-01

    The present study investigated caffeinated beverage consumption and screen time in the association with excessive daytime sleepiness (EDS) and sleep duration. We conducted a cross-sectional study including 249 Korean male high school students. These participants responded to a questionnaire inquiring the information on lifestyle factors, consumption of caffeinated beverages, time spent for screen media, and sleep duration as well as to the Epworth Sleepiness Scale (ESS) questionnaire. EDS was...

  13. Drug-induced liver injury

    DEFF Research Database (Denmark)

    Nielsen, Mille Bækdal; Ytting, Henriette; Skalshøi Kjær, Mette

    2017-01-01

    OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors...... that DILI may be severe and run a fatal course, and that bilirubin and INR levels may predict poor outcome....

  14. Rhabdomyolysis induced by antiepileptic drugs: characteristics, treatment and prognosis.

    Science.gov (United States)

    Jiang, Wei; Wang, Xuefeng; Zhou, Shengnian

    2016-01-01

    Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.

  15. Antipsychotic-induced somnolence in mothers with schizophrenia.

    Science.gov (United States)

    Seeman, Mary V

    2012-03-01

    Although it is known that many antipsychotic drugs, at the doses prescribed for schizophrenia, are sedative and cause daytime drowsiness, the effect of potentially diminished vigilance on parenting parameters has not been studied. The aim of this paper is to advise clinicians about sedative load in mothers who are prescribed antipsychotic medication. A Medline search was conducted into the sedative effects of antipsychotics, with the following search terms: sleep; sedation; somnolence; wakefulness; antipsychotics; schizophrenia, parenting, maternal behavior, and custody. The results showed that antipsychotic drugs differ in their propensity to induce sedation and do so via their effects on a variety of neurotransmitter systems. It is important to note that mothers with schizophrenia risk losing custody of their infants if they are perceived as potentially neglectful because of excessive daytime sleepiness. Clinicians must choose antipsychotic medications carefully and monitor for sedative effects whenever the patient has important responsibilities that require the maintenance of vigilance.

  16. Correntropy measures to detect daytime sleepiness from EEG signals

    International Nuclear Information System (INIS)

    Melia, Umberto; Vallverdú, Montserrat; Caminal, Pere; Guaita, Marc; Montserrat, Josep M; Vilaseca, Isabel; Salamero, Manel; Gaig, Carles; Santamaria, Joan

    2014-01-01

    Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders and has a great impact on patients’ lives. While many studies have been carried out in order to assess daytime sleepiness, automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on correntropy function analysis of EEG signals was proposed in order to detect patients suffering from EDS. Multichannel EEG signals were recorded during five Maintenance of Wakefulness Tests (MWT) and Multiple Sleep Latency Tests (MSLT) alternated throughout the day for patients suffering from sleep disordered breathing (SDB). A group of 20 patients with EDS was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60 s EEG windows in a waking state. Measures obtained from the cross-correntropy function (CCORR) and auto-correntropy function (ACORR) were calculated in the EEG frequency bands: δ, 0.1–4 Hz; θ, 4–8 Hz; α, 8–12 Hz; β, 12–30 Hz; total band TB, 0.1–45 Hz. These functions permitted the quantification of complex signal properties and the non-linear couplings between different areas of the scalp. Statistical differences between EDS and WDS groups were mainly found in the β band during MSLT events (p-value < 0.0001). The WDS group presented more complexity in the occipital zone than the EDS group, while a stronger nonlinear coupling between the occipital and frontal regions was detected in EDS patients than in the WDS group. At best, ACORR and CCORR measures yielded sensitivity and specificity above 80% and the area under ROC curve (AUC) was above 0.85 in classifying EDS and WDS patients. These performances represent an improvement with respect to classical EEG indices applied in the same database (sensitivity and specificity were never above 80% and AUC was under 0.75). (paper)

  17. An Update on Drug-induced Liver Injury.

    Science.gov (United States)

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  18. Sleep and sleepiness in environmental intolerances: a population-based study.

    Science.gov (United States)

    Nordin, Maria; Nordin, Steven

    2016-08-01

    About one fourth of the general population report environmental intolerance (EI) to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs), and/or sounds. EI sufferers show various clinical features, of which sleep disturbance is one. Sleep disturbance is common also in the general population, but it is not known whether the disturbance is more prominent in EI sufferers than in individuals who do not experience EI. Therefore, EI was compared on various sleep aspects with referents without EI. A population-based sample of 3406 individuals, aged 18-79 years, was recruited from Northern Sweden. Sleep quality, non-restorative sleep, daytime sleepiness, obstructive breathing, and nocturnal insomnia were assessed with the Karolinska Sleep Questionnaire. Single questions assessed time slept, amount of hours of needed sleep, and extent of enough time slept. All four EI groups, compared to the referents, reported significantly poorer sleep quality, more non-restorative sleep, more daytime sleepiness, more obstructive breathing and higher prevalence of nocturnal insomnia than the referents. Nocturnal insomnia was an important factor for EI groups attributing their most prevalent symptoms to chemicals and sounds, irrespective of distress and certain syndromes. None of the EI groups differed significantly from the referents on time slept, but reported needing more sleep time (the EMF-intolerance group showing only a tendency), and all four groups reported to perceive enough sleep to a significantly lesser extent. Sleep disturbance and daytime sleepiness are more common in individuals reporting EI compared to normal referents. Moreover, nocturnal insomnia is an important symptom in its own right in various types of EI. This evokes the question of whether or not sleep therapy may attenuate the severity of the EI. Copyright © 2016. Published by Elsevier B.V.

  19. Effects of psychotropic drugs and psychiatric illness on vocational aptitude and interest assessment.

    Science.gov (United States)

    Helmes, E; Fekken, G C

    1986-07-01

    This study examined the vocational aptitude and interest scores of 326 inpatients at a large urban psychiatric hospital. The inpatient group performed significantly below the adult normative mean on eight of nine General Aptitude Test Battery (GATB) aptitude measures; the single exception was Verbal Aptitude. Further, GATB aptitude scores (adjusted for age and education) were significantly lower for patients who were receiving (N = 210) psychotropic medication than for patients who were not receiving (N = 114) psychotropic medication, again with the exception of Verbal Aptitude. Differentiation of patients into subsamples who were receiving particular drugs or drug combinations indicated that phenothiazines in combination with Anti-Parkinsonians were associated with the poorest GATB performances. Interestingly, self-reported vocational interests were not related in any systematic fashion to receiving medication. A variety of explanations that may account for these findings, including drug side-effects and severity or type of psychiatric disorder, were investigated. Implications for vocational counselors were discussed.

  20. A case-control field study on the relationships among type 2 diabetes, sleepiness and habitual caffeine intake.

    Science.gov (United States)

    Urry, Emily; Jetter, Alexander; Holst, Sebastian C; Berger, Wolfgang; Spinas, Giatgen A; Langhans, Wolfgang; Landolt, Hans-Peter

    2017-02-01

    The purpose of this study was to examine the possible links between type 2 diabetes, daytime sleepiness, sleep quality and caffeine consumption. In this case-control field study, comparing type 2 diabetic ( n=134) and non-type 2 diabetic ( n=230) participants, subjects completed detailed and validated questionnaires to assess demographic status, health, daytime sleepiness, sleep quality and timing, diurnal preference, mistimed circadian rhythms and habitual caffeine intake. All participants gave saliva under standardised conditions for CYP1A2 genotyping and quantification of caffeine concentration. Hierarchical linear regression analyses examined whether type 2 diabetes status was associated with caffeine consumption. Type 2 diabetic participants reported greater daytime sleepiness ( p=0.001), a higher prevalence of sleep apnoea ( p=0.005) and napping ( p=0.008), and greater habitual caffeine intake ( pcaffeine concentration at bedtime ( p=0.01). Multiple regression analyses revealed that type 2 diabetes status was associated with higher self-reported caffeine consumption ( pcaffeine ( pcaffeine intake. Subjective sleep and circadian estimates were similar between case and control groups. Type 2 diabetic patients may self-medicate with caffeine to alleviate daytime sleepiness. High caffeine intake reflects a lifestyle factor that may be considered when promoting type 2 diabetes management.

  1. Association of sociodemographic, lifestyle, and health factors with sleep quality and daytime sleepiness in women: findings from the 2007 National Sleep Foundation "Sleep in America Poll".

    Science.gov (United States)

    Baker, Fiona C; Wolfson, Amy R; Lee, Kathryn A

    2009-06-01

    To investigate factors associated with poor sleep quality and daytime sleepiness in women living in the United States. Data are presented from the National Sleep Foundation's 2007 Sleep in America Poll that included 959 women (18-64 years of age) surveyed by telephone about their sleep quality, daytime sleepiness, and sociodemographic, health, and lifestyle factors. Poor sleep quality was reported by 27% and daytime sleepiness was reported by 21% of respondents. Logistic multivariate regression analyses revealed that poor sleep quality and daytime sleepiness were both independently associated with poor health, having a sleep disorder, and psychological distress. Also, multivariate analyses showed that women who consumed more caffeinated beverages and those who had more than one job were more likely to report poor sleep quality but not daytime sleepiness. Daytime sleepiness, on the other hand, was independently associated with being black/African American, younger, disabled, having less education, and daytime napping. Poor sleep quality and daytime sleepiness are common in American women and are associated with health-related, as well as sociodemographic, factors. Addressing sleep-related complaints in women is important to improve their daytime functioning and quality of life.

  2. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  3. PET imaging of dopamine transporters with [18F]FE-PE2I: Effects of anti-Parkinsonian drugs

    International Nuclear Information System (INIS)

    Bang, Ji-In; Jung, In Soon; Song, Yoo Sung; Park, Hyun Soo; Moon, Byung Seok; Lee, Byung Chul; Kim, Sang Eun

    2016-01-01

    Purpose: This study aimed to assess the striatal [ 18 F]FE-PE2I binding and the immunohistochemical stain of tyrosine hydroxylase (TH) in the striatum, and to evaluate the effects of therapeutic drugs on [ 18 F]FE-PE2I binding. Methods: Dynamic PET/CT of [ 18 F]FE-PE2I was performed in Parkinson’s disease (PD) rat models, induced by the unilateral injection of 6-OHDA into the striatum. A simplified reference tissue model method was used to calculate the striatal binding potential (striatal BP ND ). Each of the four normal rats was pretreated with pramipexole, amantadine, and escitalopram 30 min before [ 18 F]FE-PE2I injection. The effect of L-DOPA combined with benserazide was assessed in the normal and PD rats. Results: The BP ND was significantly lower in the lesioned striatum than in the striatum of the normal rats. After the pretreatment with pramipexole, amantadine, and escitalopram, the values of the striatal BP ND did not differ from those of the controls. The pretreatment with L-DOPA/benserazide, however, significantly reduced the striatal BP ND . The striatal BP ND of the PD rats with L-DOPA/benserazide pretreatment was not different from that of the same PD rats with placebo treatment. Conclusion: [ 18 F]FE-PE2I may be used as a radioligand for the in-vivo imaging of the DAT. In the normal rats, [ 18 F]FE-PE2I binding is unaffected by pramipexole, amantadine, and escitalopram. L-DOPA/benserazide does not affect the striatal [ 18 F]FE-PE2I binding in PD rats

  4. Breathing disturbances without hypoxia are associated with objective sleepiness in sleep apnea

    DEFF Research Database (Denmark)

    Koch, Henriette; Schneider, Logan Douglas; Finn, Laurel A

    2017-01-01

    analyzed with our automated algorithm, developed to detect breathing disturbances and desaturations. Breathing events were time-locked to desaturations, resulting in 2 indices - desaturating (H-BDI) and non-desaturating (NH-BDI) events - regardless of arousals. Measures of subjective (Epworth Sleepiness...... Scale) and objective (2,981 multiple sleep latency tests from a subset of 865 subjects) sleepiness were analyzed, in addition to clinically relevant clinicodemographic variables. Hypertension was defined as BP ≥140/90 or antihypertensive use. H-BDI, but not NH-BDI, correlated strongly with SDB severity...... indices that included hypoxia (r≥0.89, p≤0.001 with 3% ODI and AHI with 4%-desaturations). A doubling of desaturation-associated events was associated with hypertension prevalence, which was significant for ODI but not H-BDI (3% ODI OR=1.06, 95% CI=1.00-1.12, p...

  5. Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha.

    Directory of Open Access Journals (Sweden)

    Jennifer Adamski

    Full Text Available Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1. In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1α stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1α in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1α. Inhibition of the phosphoinositide 3-kinase (PI3K pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target

  6. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  7. Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

    Science.gov (United States)

    Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

    2013-01-01

    Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of

  8. Insomnia, Sleepiness, and Depression in Adolescents Living in Residential Care Facilities

    Science.gov (United States)

    Moreau, Vincent; Belanger, Lynda; Begin, Gilles; Morin, Charles M.

    2009-01-01

    The main objective of this study was to document sleep patterns and disturbances reported by youths temporarily living in residential care facilities. A secondary objective was to examine the relationships between sleep disturbances and mood and daytime sleepiness. A self-reported questionnaire on sleep patterns and habits assessing duration,…

  9. Insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder in nurses having less than 11 hours in-between shifts.

    Directory of Open Access Journals (Sweden)

    Maria Fagerbakke Eldevik

    Full Text Available STUDY OBJECTIVE: To assess if less than 11 hours off work between work shifts (quick returns was related to insomnia, sleepiness, fatigue, anxiety, depression and shift work disorder among nurses. METHODS: A questionnaire including established instruments measuring insomnia (Bergen Insomnia Scale, sleepiness (Epworth Sleepiness Scale, fatigue (Fatigue Questionnaire, anxiety/depression (Hospital Anxiety and Depression Scale and shift work disorder was administered. Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no quick returns, 724 had 1-30 quick returns and 892 had more than 30 quick returns during the past year. 110 nurses did not report the number of quick returns during the past year. The prevalence of insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder was calculated within the three groups of nurses. Crude and adjusted logistic regression analyses were performed to assess the relation between quick returns and such complaints. RESULTS: We found a significant positive association between quick returns and insomnia, excessive sleepiness, excessive fatigue and shift work disorder. Anxiety and depression were not related to working quick returns. CONCLUSIONS: There is a health hazard associated with quick returns. Further research should aim to investigate if workplace strategies aimed at reducing the number of quick returns may reduce complaints among workers.

  10. Insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder in nurses having less than 11 hours in-between shifts.

    Science.gov (United States)

    Eldevik, Maria Fagerbakke; Flo, Elisabeth; Moen, Bente Elisabeth; Pallesen, Ståle; Bjorvatn, Bjørn

    2013-01-01

    To assess if less than 11 hours off work between work shifts (quick returns) was related to insomnia, sleepiness, fatigue, anxiety, depression and shift work disorder among nurses. A questionnaire including established instruments measuring insomnia (Bergen Insomnia Scale), sleepiness (Epworth Sleepiness Scale), fatigue (Fatigue Questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale) and shift work disorder was administered. Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no quick returns, 724 had 1-30 quick returns and 892 had more than 30 quick returns during the past year. 110 nurses did not report the number of quick returns during the past year. The prevalence of insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder was calculated within the three groups of nurses. Crude and adjusted logistic regression analyses were performed to assess the relation between quick returns and such complaints. We found a significant positive association between quick returns and insomnia, excessive sleepiness, excessive fatigue and shift work disorder. Anxiety and depression were not related to working quick returns. There is a health hazard associated with quick returns. Further research should aim to investigate if workplace strategies aimed at reducing the number of quick returns may reduce complaints among workers.

  11. Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Samuel J Bolitho

    Full Text Available INTRODUCTION: Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. METHODS: Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. RESULTS: Patients with PD had a 225% increase in the mean nap time per day (minutes as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001. Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. CONCLUSION: This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime

  12. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yu; Zhang, Xiaojin, E-mail: zhangxj@cug.edu.cn [China University of Geosciences, Faculty of Materials Science and Chemistry (China)

    2017-05-15

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(ε-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  13. [Drug-induced fever: a diagnosis to remember].

    Science.gov (United States)

    Vodovar, D; Le Beller, C; Lillo-Le-Louet, A; Hanslik, T; Megarbane, B

    2014-03-01

    Drug fever (DF) is a febrile reaction induced by a drug without additional clinical features like skin eruption. This adverse drug reaction is probably common but under diagnosed. While its outcome is generally favourable, DF generates unnecessary diagnostic procedures as well as hospitalisations or hospitalisation prolongations. Clinical presentation and biological findings are not specific. Fever is generally well tolerated but may be accompanied by general symptoms mimicking sepsis. Moderate biological disorders could be expected, including elevation or decrease in white blood cell count, eosinophilia, liver cytolysis, and increased C-reactive protein. An infection should be systematically ruled out. Clinical or biological signs of severity should question DF diagnosis. When DF is suspected, the involved drug(s) should be stopped after a reliable assessment of imputability. Antibiotics represent the most often implicated drugs. Fever disappearance after discontinuing the suspected drug is the cornerstone of DF diagnosis. Before stopping the administration of the suspected drug(s), a risk/benefit ratio assessment is necessary. Consistently, it may be complicated to stop an antimicrobial drug when treating an infection or an immunosuppressive drug if required. Copyright © 2013. Published by Elsevier SAS.

  14. Cross-Sectional Study of Obstructive Sleep Apnea Syndrome in Japanese Public Transportation Drivers: Its Prevalence and Association With Pathological Objective Daytime Sleepiness.

    Science.gov (United States)

    Sasai-Sakuma, Taeko; Kikuchi, Katsunori; Inoue, Yuichi

    2016-05-01

    This study investigates obstructive sleep apnea syndrome (OSAS) prevalence among Japanese occupational drivers and factors associated with a pathological level of objective daytime sleepiness. Portable monitoring device (PMD) screening was applied to 2389 Japanese male public transportation traffic drivers. Nocturnal polysomnography (n-PSG) and multiple sleep latency tests (MSLT) were administered to subjects with apnea-hypopnea index (AHI) at least 15 on PMD. In all, 235 subjects were diagnosed as having OSAS (9.8%). AHI on n-PSG at least 40 and Epworth Sleepiness Scale score at least 11 were extracted as factors associated with mean sleep latency on MSLT less than 5 minutes. Prevalence of OSAS in male Japanese public transportation traffic drivers was 9.8% or greater. Individuals aware of excessive daytime sleepiness and with severe OSAS were inferred as exhibiting a pathological level of objective daytime sleepiness.

  15. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug-induced

  16. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    International Nuclear Information System (INIS)

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug-induced

  17. Sleepiness, occlusion, dental arch and palatal dimensions in children attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Andersson, H; Sonnesen, L

    2018-04-01

    This was to compare sleepiness, occlusion, dental arch and palatal dimensions between children with attention deficit hyperactivity disorders (ADHD) and healthy children (control group). 15 children with ADHD (10 boys, 5 girls, mean age 10.98 years) and 36 healthy age matched children (21 boys, 15 girls, mean age 10.60 years) were included. Intra-oral three-dimensional scans of the teeth and palate were performed to evaluate the occlusion, dental arch and palatal dimensions. Sleepiness was evaluated from the questionnaires. The differences between the two groups were analysed by Fisher's exact test and general linear models adjusted for age and gender. The ADHD children had a significantly narrower dental arch at the gingival level of the canines (p ADHD children snored significantly more (p ADHD children had a tendency to sleep fewer hours during the night (p = 0.066) and felt inadequately rested in the morning (p = 0.051) compared to the controls. The results indicate that sleepiness and palatal width, especially the more anterior skeletal part of the palate, may be affected in children with ADHD. The results may prove valuable in the diagnosis and treatment planning of children with ADHD. Further studies are needed to investigate sleep and dental relations in children with ADHD.

  18. Associations between physical activity, sedentary time, sleep duration and daytime sleepiness in US adults.

    Science.gov (United States)

    McClain, James J; Lewin, Daniel S; Laposky, Aaron D; Kahle, Lisa; Berrigan, David

    2014-09-01

    To examine the associations between objectively measured physical activity (PA) or sedentary behavior and self-reported sleep duration or daytime sleepiness in a nationally representative sample of healthy US adults (N=2128). We report analyses of four aspects of sedentary behavior and PA derived from accelerometry data (minutes of sedentary time, activity counts/minute, Minutes of Moderate and Vigorous PA [MVPA], and MVPA in 10-minute bouts) versus self-report of sleep duration and frequency of daytime sleepiness from the 2005-2006 National Health and Nutrition Examination Survey. Age and sex dependence of associations between PA and sleep were observed. Aspects of PA were significantly lower in adults reporting more frequent daytime sleepiness in younger (20-39) and older (≥ 60) age groups, but not in middle-aged (40-59), respondents. In younger respondents, PA increased with sleep duration, but in middle aged and older respondents PA was either unrelated to sleep duration or lower in those reporting ≥ 8 h of sleep. Objectively measured sedentary time showed limited evidence of associations with sleep duration. Further research delineating the relationships between sleep and PA is important because both activities have been implicated in diverse health outcomes as well as in the etiology of obesity. Published by Elsevier Inc.

  19. Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis

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    Bliwise Donald L

    2003-11-01

    Full Text Available Abstract Background Although considerable progress has been made in the treatment of chronic kidney disease, compromised quality of life continues to be a significant problem for patients receiving hemodialysis (HD. However, in spite of the high prevalence of sleep complaints and disorders in this population, the relationship between these problems and quality of life remains to be well characterized. Thus, we studied a sample of stable HD patients to explore relationships between quality of life and both subjective and objective measures of nocturnal sleep and daytime sleepiness Methods The sample included forty-six HD patients, 24 men and 22 women, with a mean age of 51.6 (10.8 years. Subjects underwent one night of polysomnography followed the next morning by a Multiple Sleep Latency Test (MSLT, an objective measure of daytime sleepiness. Subjects also completed: 1 a brief nocturnal sleep questionnaire; 2 the Epworth Sleepiness Scale; and, 3 the Quality of Life Index (QLI, Dialysis Version which provides an overall QLI score and four subscale scores for Health & Functioning (H&F, Social & Economic (S&E, Psychological & Spiritual (P&S, and Family (F. (The range of scores is 0 to 30 with higher scores indicating better quality of life. Results The mean (standard deviation; SD of the overall QLI was 22.8 (4.0. The mean (SD of the four subscales were as follows: H&F – 21.1 (4.7; S&E – 22.0 (4.8; P&S – 24.5 (4.4; and, F – 26.8 (3.5. H&F (rs = -0.326, p = 0.013 and F (rs = -0.248, p = 0.048 subscale scores were negatively correlated with periodic limb movement index but not other polysomnographic measures. The H&F subscale score were positively correlated with nocturnal sleep latency (rs = 0.248, p = 0.048 while the H&F (rs = 0.278, p = 0.030 and total QLI (rs = 0.263, p = 0.038 scores were positively associated with MSLT scores. Both of these latter findings indicate that higher life quality is associated with lower sleepiness levels. ESS

  20. Individual and average responses of sleep quality and daytime sleepiness after four weeks of strength training in adolescents

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    Maria Julia Lyra

    2018-01-01

    Full Text Available Abstract Aims: To analyze the average and individual responses of sleep quality and daytime sleepiness in adolescents after four weeks of strength training. Methods: 19 adolescents with sleep problems recruited in the Federal Institute of Pernambuco, were subject to anthropometric evaluations as well as those for body composition assessment, a 1 repetition maximum test, the sleep parameters (Pittsburgh Sleep Quality Index-PSQI and Epworth Sleepiness Scale-ESS and were submitted to four weeks of strength-training, performed alternately by segment, two sessions per week, according to recommendations for this population. Results: A decrease in the average PSQI score was observed (10.3±3.3 vs 8.8±4.0; p=0.006, but not in ESS (p>0.05, after intervention. The individual analyses demonstrated that ~63% of adolescents experienced reductions ≥ 3 points in the PSQI and ~58% of them experienced reductions ≥ 3 points in the measure of daytime sleepiness. The prevalence of poor sleep quality and daytime sleepiness reduced from 84.2% to 68.4% and from 52.6% to 31.6%, respectively. The comparisons of high and low responders to exercise training show that adolescents who reduced ≥3 points in the score of a least one sleep parameter presented lower weight, fat mass, and fat percentage (p<0.05. Conclusion: A short-term strength-training program is able to improve global sleep quality, but not daytime sleepiness in adolescents. Furthermore, the changes after training are highly heterogeneous. Further studies are required to better understand the effects of strength training on sleep parameters of adolescents.

  1. The prevalence of excessive daytime sleepiness among academic physicians and its impact on the quality of life and occupational performance.

    Science.gov (United States)

    Ozder, Aclan; Eker, Hasan Huseyin

    2015-01-01

    Sleep disorders can affect health and occupational performance of physicians as well as outcomes in patients. The purpose of this study was to assess the prevalence of excessive daytime sleepiness (EDS) measured by the Epworth Sleepiness Scale (ESS) among academic physicians at a tertiary academic medical center in an urban area in the northwest region of Turkey, and to establish a relationship between the self-perceived sleepiness and the quality of life using the EuroQol-5 dimensions (EQ-5D). A questionnaire prepared by the researchers after scanning the literature on the subject was e-mailed to the academic physicians of a tertiary academic medical center in Istanbul. The ESS and the EQ-5D were also included in the survey. The e-mail database of the institution directory was used to compile a list of active academic physicians who practiced clinical medicine. Paired and independent t tests were used for the data analysis at a significance level of p academic physicians were e-mailed and a total of 252 subjects replied resulting in a 63.6% response rate. There were 84 (33.3%) female and 168 (66.7%) male academic physicians participating in the study. One hundred and eight out of 252 (42.8%) academic physicians were taking night calls (p sleep and 84 (33.3%) reported napping daily (p 10) (p academic physicians was associated with a poorer quality of life (p academic physicians suffered from sleepiness. There was an association between the poor quality of life and daytime sleepiness. There was also a positive relationship between habitual napping and being sleepy during the day. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  2. Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

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    Jiezhong Chen

    2017-11-01

    Full Text Available Antipsychotic drugs (APDs are widely prescribed to control various mental disorders. As mental disorders are chronic diseases, these drugs are often used over a life-time. However, APDs can cause serious glucometabolic side-effects including type 2 diabetes and hyperglycaemic emergency, leading to medication non-compliance. At present, there is no effective approach to overcome these side-effects. Understanding the mechanisms for APD-induced diabetes should be helpful in prevention and treatment of these side-effects of APDs and thus improve the clinical outcomes of APDs. In this review, the potential mechanisms for APD-induced diabetes are summarized so that novel approaches can be considered to relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple mechanisms: (1 APDs can inhibit the insulin signaling pathway in the target cells such as muscle cells, hepatocytes and adipocytes to cause insulin resistance; (2 APD-induced obesity can result in high levels of free fatty acids (FFA and inflammation, which can also cause insulin resistance. (3 APDs can cause direct damage to β-cells, leading to dysfunction and apoptosis of β-cells. A recent theory considers that both β-cell damage and insulin resistance are necessary factors for the development of diabetes. In high-fat diet-induced diabetes, the compensatory ability of β-cells is gradually damaged, while APDs cause direct β-cell damage, accounting for the severe form of APD-induced diabetes. Based on these mechanisms, effective prevention of APD-induced diabetes may need an integrated approach to combat various effects of APDs on multiple pathways.

  3. Drug-induced pulmonary arterial hypertension: a recent outbreak

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    Gérald Simonneau

    2013-09-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH.

  4. Emotional content of dreams in obstructive sleep apnea hypopnea syndrome patients and sleepy snorers attending a sleep-disordered breathing clinic.

    Science.gov (United States)

    Fisher, Samantha; Lewis, Keir E; Bartle, Iona; Ghosal, Robin; Davies, Lois; Blagrove, Mark

    2011-02-15

    To assess prospectively the emotional content of dreams in individuals with the obstructive sleep apnea hypopnea syndrome (OSAHS) and sleepy snorers. Prospective observational study. Forty-seven patients with sleepiness and snoring attending a sleep-disordered breathing clinic, completed a morning diary concerning pleasantness/unpleasantness of their dreams for 10 days, and then had AHI assessed by a limited-channel home sleep study. Participants and groups: Sleepy snorers, AHI dreams and nightmares during the diary period. The AHI ≥ 15 group were significantly higher on dream unpleasantness than were the sleepy snorers (p dream emotions (Levene test for homogeneity of variance between the 3 groups, p = 0.018). Mean daytime anxiety and daytime depression were significantly correlated with mean dream unpleasantness and with mean number of nightmares over the diary period. Patients with AHI ≥ 15 had more emotionally negative dreams than patients with AHI dream emotion decreased with increasing AHI, possibly because sleep fragmentation with increasing AHI results in fewer and shorter dreams, in which emotions are rarer.

  5. Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

    Science.gov (United States)

    Frank, Matthew G; Watkins, Linda R; Maier, Steven F

    2011-06-01

    Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Two- and 4-hour bright-light exposures differentially effect sleepiness and performance the subsequent night.

    Science.gov (United States)

    Thessing, V C; Anch, A M; Muehlbach, M J; Schweitzer, P K; Walsh, J K

    1994-03-01

    The effect of two durations of bright light upon sleepiness and performance during typical night shift hours was assessed. Thirty normal, healthy young adults participated in a 2-night protocol. On the 1st night subjects were exposed to bright or dim light beginning at 2400 hours, under one of the following three conditions: bright light for 4 hours, dim light for 2 hours followed by bright light for 2 hours or dim light for 4 hours. Following light exposure, subjects remained awake until 0800 hours in a dimly lit room and slept in the laboratory between 0800 and 1600 hours, during which time sleep was estimated with actigraphy. Throughout the 2nd night, the multiple sleep latency test (MSLT), simulated assembly line task (SALT) performance, and subjective sleepiness were recorded. The single, 4-hour exposure to bright light was found to significantly increase MSLT scores and improve SALT performance during the early morning hours on the night following bright-light exposure. No significant effects were noted with a 2-hour exposure. The most likely explanation for these findings is a phase delay in the circadian rhythm of sleepiness-alertness.

  7. Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition

    Energy Technology Data Exchange (ETDEWEB)

    Shirakawa, Maho; Sekine, Shuichi; Tanaka, Ayaka [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan); Horie, Toshiharu [Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo (Japan); Ito, Kousei, E-mail: itokousei@chiba-u.jp [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan)

    2015-10-01

    The risk of drug-induced liver injury (DILI) is of great concern to the pharmaceutical industry. It is well-known that metabolic activation of drugs to form toxic metabolites (TMs) is strongly associated with DILI onset. Drug-induced mitochondrial dysfunction is also strongly associated with increased risk of DILI. However, it is difficult to determine the target of TMs associated with exacerbation of DILI because of difficulties in identifying and purifying TMs. In this study, we propose a sequential in vitro assay system to assess TM formation and their ability to induce mitochondrial permeability transition (MPT) in a one-pot process. In this assay system, freshly-isolated rat liver mitochondria were incubated with reaction solutions of 44 test drugs preincubated with liver microsomes in the presence or absence of NADPH; then, NADPH-dependent MPT pore opening was assessed as mitochondrial swelling. In this assay system, several hepatotoxic drugs, including benzbromarone (BBR), significantly induced MPT in a NADPH-dependent manner. We investigated the rationality of using BBR as a model drug, since it showed the most prominent MPT in our assay system. Both the production of a candidate toxic metabolite of BBR (1′,6-(OH){sub 2} BBR) and NADPH-dependent MPT were inhibited by several cytochrome P450 (CYP) inhibitors (clotrimazole and SKF-525A, 100 μM). In summary, this assay system can be used to evaluate comprehensive metabolite-dependent MPT without identification or purification of metabolites. - Highlights: • We constructed a sequential assay system for toxic metabolite induced MPT in one pot. • 14 drugs (e.g. benzbromarone (BBR)) induced toxic metabolite dependent MPT. • Both the production of toxic metabolite and MPT could be inhibited by CYP inhibitors. • This system could evaluate the comprehensive MPT without purification of metabolites.

  8. The sleepy teenager - diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLandtblom

    2014-08-01

    Full Text Available The sleepy teenager is a diagnostic challenge because the problems may be physiological or pathological, with behavioural, social and pychological expressions. It is of great importance that health staff that encounter young people with sleep disturbance have good knowledge about the diseases that must be excluded. Narcolepsy, periodic hypersomnia like Kleine Levin syndrome, delayed sleep phase syndrome and obstructive sleep apnoea syndrome, depression and substance use as well as fatigue from chronic disease like multiple sclerosis should be investigated. Clinical assessment, neurophysiological and laboratory investigations constitute important support in these investigations. Functional methods, for example fMRI, are being developed. The role of computer gaming and use of social media in the night is discussed in relation to these diseases. Cognitive dysfunction may develop with several of the conditions. There is need for increased awareness of how to investigate sleep disturbance in children and young people.

  9. Association between commercial vehicle driver at-fault crashes involving sleepiness/fatigue and proximity to rest areas and truck stops.

    Science.gov (United States)

    Bunn, Terry L; Slavova, Svetla; Rock, Peter J

    2017-11-22

    There is ongoing concern at the national level about the availability of adequate commercial vehicle rest areas and truck stops for commercial vehicle drivers to rest or to wait for a delivery window. A retrospective case-control study was conducted to determine the association between the occurrence of sleepiness/fatigue-related (cases) vs. all other human factor-related commercial vehicle driver at-fault crashes (controls) and proximity to rest areas, weigh stations with rest havens, and truck stops. Commercial vehicle driver at-fault crashes involving sleepiness/fatigue were more likely to occur on roadways where the nearest rest areas/weigh stations with rest havens/truck stops were located 20 miles or more from the commercial vehicle crash site (Odds Ratio [OR]=2.32; Confidence Interval [CI] 1.615, 3.335] for 20-39.9 miles vs. commercial vehicle at-fault driver crashes with human factors other than sleepiness/fatigue cited in crash reports. Commercial vehicle driver at-fault crashes involving sleepiness/fatigue also were more likely to occur on parkways compared to interstates (adjusted OR=3.747 [CI 2.83, 4.95]), during nighttime hours (adjusted OR=6.199 [CI 4.733, 8.119]), and on dry pavement (adjusted OR 1.909, [CI 1.373, 2.655]). The use of statewide crash data analysis coupled with ArcGIS mapping capabilities provided the opportunity to both statistically determine and to visualize the association between rest area/weigh station with rest haven/truck stop distance and the occurrence of commercial vehicle driver at-fault crashes involving sleepiness/fatigue. Implementation and evaluation of commercial vehicle employer policies and interventions such as the use of commercial vehicle driver fatigue alert systems may help to reduce fatigue and sleepiness in commercial vehicle drivers. These results can be used by state and local highway transportation officials to inform and increase truck parking availability, especially on parkways. Copyright © 2017

  10. Modification of the Epworth Sleepiness Scale in Central China.

    Science.gov (United States)

    Zhang, Jin Nong; Peng, Bo; Zhao, Ting Ting; Xiang, Min; Fu, Wei; Peng, Yi

    2011-12-01

    The well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China. A Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was administered to 122 patients in central China with suspected SDB [among them, 119 cases met the minimal diagnostic criteria for obstructive sleep apnea by sleep study, e.g., apnea and hypopnea index (AHI) ≥ 5 h(-1)] and 117 healthy central Chinese volunteers without SDB. Multivariate exploratory techniques were used for item validation. The unreliable item in the original ESS was replaced by the eligible backup item, thus a modified ESS (mESS) was built, and then verified. Item 8 proved to be the only unreliable item in central Chinese patients, with the least factor loading on the main factor and the lowest item-total correlation both in the 10-ISQ and in the original ESS, deletion of it would increase the Cronbach's alpha (from 0.86 to 0.87 in the 10-ISQ; from 0.83 to 0.85 in the original ESS). The mESS was subsequently built by replacing item 8 in the original ESS with item 10 in the 10-ISQ. Verification with patients' responses revealed that the mESS was a single-factor questionnaire with good internal consistency (Cronbach's alpha = 0.86). The sum score of the mESS not only correlated with AHI (P < 0.01) but was also able to discriminate the severity of obstructive apnea (P < 0.01). Nasal CPAP treatment for severe OSA reduced the score significantly (P < 0.001). The performance of the mESS was poor in evaluating normal subjects. The mESS improves the validity of ESS for our patients. Therefore, it is justified to use it instead of the original one in assessment of EDS for patients with SDB

  11. Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent

    Directory of Open Access Journals (Sweden)

    Kura AU

    2013-03-01

    Full Text Available Aminu Umar Kura,1 Samer Hasan Hussein Al Ali,2 Mohd Zobir Hussein,3 Sharida Fakurazi,1,4 Palanisamy Arulselvan11Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, 4Faculty of Medicine and Health Science, Pharmacology Unit, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: A new layered organic–inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl alanine (levodopa, intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nanocomposite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w. A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure.Keywords: levodopa, layered double hydroxides, coprecipitation, sustained release

  12. Associations of impaired sleep quality, insomnia, and sleepiness with epilepsy: A questionnaire-based case-control study.

    Science.gov (United States)

    Im, Hee-Jin; Park, Seong-Ho; Baek, Shin-Hye; Chu, Min Kyung; Yang, Kwang Ik; Kim, Won-Joo; Yun, Chang-Ho

    2016-04-01

    The purpose of this study was to document the frequency of sleep problems including poor sleep quality, excessive daytime sleepiness, and insomnia in subjects with epilepsy compared with healthy controls and to determine the factors associated with these sleep disturbances. We recruited 180 patients with epilepsy (age: 43.2 ± 15.6 years, men: 50.0%) and 2836 healthy subjects (age: 44.5 ± 15.0 years, men: 49.8%). Sleep and the anxiety/mood profiles were measured using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, Goldberg Anxiety Scale, and Patient Health Questionnaire-9 depression scale. Associations of sleep problems with epilepsy and other factors were tested by multiple logistic regression analysis, adjusted for age, gender, body mass index, alcohol intake, smoking, perceived sleep insufficiency, and habitual snoring. Sleep disturbances were more common in the group with epilepsy than in the controls (53.3% vs. 25.5%; pinsomnia were significantly associated with epilepsy (odds ratio [95% confidence interval]: 3.52 [2.45-5.05], 2.10 [1.41-3.12], 5.91 [3.43-10.16], respectively). Depressive mood, anxiety, and perceived sleep insufficiency contributed to the presence of sleep disturbances. In the group with epilepsy, seizure remission for the past year related to a lower frequency of insomnia, whereas age, sex, type of epilepsy, and number of antiepileptic drugs were not correlated with sleep problems. Epilepsy was significantly associated with the higher frequency of sleep disturbances, which supports the importance of screening sleep problems in patients with epilepsy and providing available intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Real driving at night - Predicting lane departures from physiological and subjective sleepiness

    NARCIS (Netherlands)

    Hallvig, D.; Anund, A.; Fors, C.; Kecklund, L.G.; Äkerstedt, T.

    2014-01-01

    Only limited information is available on how driving performance relates to physiological and subjective sleepiness on real roads. This relation was the focus of the present study. 33 volunteers drove for 90 min on a rural road during the afternoon and night in an instrumented car, while

  14. Objective and quantitative analysis of daytime sleepiness in physicians after night duties.

    Science.gov (United States)

    Wilhelm, Barbara J; Widmann, Anja; Durst, Wilhelm; Heine, Christian; Otto, Gerhard

    2009-06-01

    Work place studies often have the disadvantage of lacking objective data less prone to subject bias. The aim of this study was to contribute objective data to the discussion about safety aspects of night shifts in physicians. For this purpose we applied the Pupillographic Sleepiness Test (PST). The PST allows recording and analyses of pupillary sleepiness-related oscillations in darkness for 11 min in the sitting subject. The parameter of evaluation is the Pupillary Unrest Index (PUI; mm/min). For statistical analysis the natural logarithm of this parameter is used (lnPUI). Thirty-four physicians were examined by the PST and subjective scales during the first half of the day. Data taken during a day work period (D) were compared to those taken directly after night duty (N) by a Wilcoxon signed rank test. Night duty caused a mean sleep reduction of 3 h (Difference N-D: median 3 h, minimum 0 h, maximum 7 h, p home.

  15. Cognitive Performance, Sleepiness, and Mood in Partially Sleep Deprived Adolescents: The Need for Sleep Study.

    Science.gov (United States)

    Lo, June C; Ong, Ju Lynn; Leong, Ruth L F; Gooley, Joshua J; Chee, Michael W L

    2016-03-01

    To investigate the effects of sleep restriction (7 nights of 5 h time in bed [TIB]) on cognitive performance, subjective sleepiness, and mood in adolescents. A parallel-group design was adopted in the Need for Sleep Study. Fifty-six healthy adolescents (25 males, age = 15-19 y) who studied in top high schools and were not habitual short sleepers were randomly assigned to Sleep Restriction (SR) or Control groups. Participants underwent a 2-w protocol consisting of 3 baseline nights (TIB = 9 h), 7 nights of sleep opportunity manipulation (TIB = 5 h for the SR and 9 h for the control groups), and 3 nights of recovery sleep (TIB = 9 h) at a boarding school. A cognitive test battery was administered three times each day. During the manipulation period, the SR group demonstrated incremental deterioration in sustained attention, working memory and executive function, increase in subjective sleepiness, and decrease in positive mood. Subjective sleepiness and sustained attention did not return to baseline levels even after 2 recovery nights. In contrast, the control group maintained baseline levels of cognitive performance, subjective sleepiness, and mood throughout the study. Incremental improvement in speed of processing, as a result of repeated testing and learning, was observed in the control group but was attenuated in the sleep-restricted participants, who, despite two recovery sleep episodes, continued to perform worse than the control participants. A week of partial sleep deprivation impairs a wide range of cognitive functions, subjective alertness, and mood even in high-performing high school adolescents. Some measures do not recover fully even after 2 nights of recovery sleep. A commentary on this article appears in this issue on page 497. © 2016 Associated Professional Sleep Societies, LLC.

  16. Prevalence and Complications of Drug-induced Seizures in Baharloo Hospital, Tehran, Iran

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    Behnam Behnoush

    2012-05-01

    Full Text Available Background: Seizure is a frequent and important finding in the field of clinical toxicology. Almost all poisons and drugs can produce seizure. We have evaluated frequency and complications of drug-induced seizure in present study. Methods: The present descriptive cross-sectional study was done on patients who were referred to Baharloo Hospital, Tehran, Iran, that had developed seizure before or after hospitalization following intoxication between 20 March 2010 and 20 March 2011. The exclusion criteria were a positive history of epilepsy, head trauma, or abnormal findings in EEG or brain CT scan. Results: Tramadol and tricyclic antidepressants were the most common causes of drug-induced seizure (31.5% and 14.7% of the cases, respectively. Overall, 6 patients (4.2% had developed persistent vegetative state in consequence of brain hypoxia, 16 patients (11.2% had died due to complications of seizure or the poisoning itself. Tramadol was the leading cause of drug-induced seizure and its morbidity and mortality. Tonic-colonic seizure was the most common type of drug-induced seizure. Seizure had occurred once in 58% of the patients, twice in 37.1% of the patients, and had been revolutionized to status epilepticus in 4.9% of them. Among the 7 patients who had developed status epilepticus, 3 cases had died. Conclusion: Appropriate measures for treatment of seizure and prevention of its complications should be taken when patients with drug poisoning are admitted into hospital, especially when the offending drug(s has a higher likelihood to induce seizure.

  17. Drug induced xerostomia in elderly individuals: An institutional study

    Directory of Open Access Journals (Sweden)

    Shishir Ram Shetty

    2012-01-01

    Full Text Available Introduction : With better health care facilities and nutritional levels the average life expectancy of Indian population has been on the rise over the years. Most of the geriatric population is under long-term medication. Aim : The aim of this study was to evaluate the synergistic effect of multiple xerostomia drugs. Materials and Methods : Unstimulated saliva was measured in 60 geriatric patients, and xerostomia questionnaire and quality-of-life scale were also administered. Results : There was a very highly significant reduction in the salivary flow rates of patients under multiple xerostomia-inducing drugs. Conclusion : The synergistic effect of the xerostomia inducing medication could be the possible factor responsible for reduced salivary flow in elderly individuals using such drugs

  18. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  19. Effect of CPAP Therapy in Improving Daytime Sleepiness in Indian Patients with Moderate and Severe OSA.

    Science.gov (United States)

    Battan, Gulshan; Kumar, Sanjeev; Panwar, Ajay; Atam, Virendra; Kumar, Pradeep; Gangwar, Anil; Roy, Ujjawal

    2016-11-01

    Obstructive Sleep Apnoea (OSA) is a highly prevalent disease and a major public health issue in India. Excessive daytime sleepiness is an almost ubiquitous symptom of OSA. Epworth Sleepiness Scale (ESS) score is a validated objective score to measure the degree of daytime sleepiness. Continuous Positive Airway Pressure (CPAP) therapy has been established as the gold standard treatment modality for OSA patients. A few Indian studies have reported the effectiveness of CPAP therapy in improving ESS scores after 1 st month of CPAP use. To observe both, short-term (one month) and long-term (three month) effects of CPAP therapy on ESS scores in moderate to severe OSA patients. The patients complaining of excessive day-time sleepiness, snoring and choking episodes during sleep, consecutively presenting to medicine OPD over a period of 2 years, were subjected to Polysomnography (PSG). Seventy-three patients with apnoea-hypopnea index (AHI) ≥15 were categorised as having moderate to severe forms of OSA (moderate OSA with AHI=15-30 and severe OSA with AHI >30), and were scheduled for an initial trial of CPAP therapy. Forty-seven patients reported good tolerance to CPAP therapy after a trial period of 2 weeks and comprised the final study group. ESS scores in these patients were recorded at the baseline, and after 1 st and 3 rd month of CPAP therapy, and statistically analysed for significance. Mean ESS score at the baseline among moderate and severe OSA patients were 13.67±2.29 and 16.56 ±1.87, respectively. ESS score in both these subgroups improved significantly to 11.63±3.79, p=0.022, CI (0.3293-4.0106)} and 14.13 ±3.74, p CPAP therapy. Likewise, mean ESS scores among moderate and severe OSA patients improved significantly to 9.84 ±2.97, p = 0.022, CI (0.3293-4.0106) and 12.29 ±3.97, p CPAP therapy. The result of the present study shows that CPAP therapy is significantly effective in improving ESS scores in Indian patients having moderate to severe OSA. Benefits

  20. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  1. Drug-induced liver toxicity and prevention by herbal antioxidants: an overview

    Directory of Open Access Journals (Sweden)

    Divya eSingh

    2016-01-01

    Full Text Available The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for medication instigated liver danger. Endorsed medications (counting acetaminophen represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group (ALFSG of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and herbal products in the treatment of various disorders led the investigators to look into their potential in countering drug-induced liver toxicity. Several plant products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less side reactions of the herbs provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed on the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication.

  2. Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges

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    Maria Adriana Rangel

    2017-01-01

    Full Text Available The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis and treatment difficulties.

  3. A survey study of the association between mobile phone use and daytime sleepiness in California high school students

    OpenAIRE

    Nathan, Nila; Zeitzer, Jamie

    2013-01-01

    Background Mobile phone use is near ubiquitous in teenagers. Paralleling the rise in mobile phone use is an equally rapid decline in the amount of time teenagers are spending asleep at night. Prior research indicates that there might be a relationship between daytime sleepiness and nocturnal mobile phone use in teenagers in a variety of countries. As such, the aim of this study was to see if there was an association between mobile phone use, especially at night, and sleepiness in a group of U...

  4. Antimalarial drug induced decrease in creatinine clearance

    NARCIS (Netherlands)

    Landewé, R. B.; Vergouwen, M. S.; Goeei The, S. G.; van Rijthoven, A. W.; Breedveld, F. C.; Dijkmans, B. A.

    1995-01-01

    To confirm the antimalarial drug induced increase of creatinine to determine the factors contributing to this effect. Patients with rheumatoid arthritis (RA) (n = 118) who have used or still use antimalarials (chloroquine or hydroxychloroquine). Serum creatinines prior to antimalarials and serum

  5. Comparison of clinical features between primary and drug-induced sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Komada Y

    2016-05-01

    Full Text Available Yoko Komada,1 Yoshikazu Takaesu,2 Kentaro Matsui,3 Masaki Nakamura,3 Shingo Nishida,3 Meri Kanno,3,† Akira Usui,3 Yuichi Inoue1,3 1Department of Somnology, 2Department of Psychiatry, Tokyo Medical University, 3Japan Somnology Center, Institute of Neuropsychiatry, Tokyo, Japan †Meri Kanno passed away on March 1, 2016 Purpose: The aim of this study was to ascertain the clinical characteristics of drug-induced sleep-related eating disorder (SRED. Patients and methods: We retrospectively reviewed the medical records of 30 patients with primary SRED (without any comorbid sleep disorders and who were not taking any possible causative medications, and ten patients with drug-induced SRED (occurrence of SRED episodes after starting nightly medication of sedative drugs, which completely resolved after dose reduction or discontinuation of the sedatives. Results: All patients with drug-induced SRED took multiple types of sedatives, such as benzodiazepines or benzodiazepine receptor agonists. Clinical features of drug-induced SRED compared with primary SRED were as follows: higher mean age of onset (40 years old in drug-induced SRED vs 26 years old in primary SRED, significantly higher rate of patients who had total amnesia during most of their SRED episodes (75.0% vs 31.8%, significantly lower rate of comorbidity of night eating syndrome (0% vs 63.3%, and significantly lower rate of history of sleepwalking (10.0% vs 46.7%. Increased doses of benzodiazepine receptor agonists may be responsible for drug-induced SRED. Conclusion: The clinical features of drug-induced SRED were different from those of primary SRED, possibly reflecting differences in the underlying mechanisms between these two categories of SREDs. Keywords: nocturnal eating syndrome, night eating, eating disorder, hypnotics, amnesia, sleepwalking, benzodiazepine

  6. Effects of an alternating work shift on air traffic controllers and the relationship with excessive daytime sleepiness and stress.

    Science.gov (United States)

    Freitas, Ângela M; Portuguez, Mirna Wetters; Russomano, Thaís; Freitas, Marcos de; Silvello, Silvio Luis da Silva; Costa, Jaderson Costa da

    2017-10-01

    To evaluate symptoms of stress and excessive daytime sleepiness (EDS) in air traffic control (ATC) officers in Brazil. Fifty-two ATC officers participated, based at three air traffic control units, identified as A, B and C. Stress symptoms were assessed using the Lipp Inventory of Stress Symptoms for Adults, and EDS by the Epworth Sleepiness Scale. The sample mean age was 37 years, 76.9% of whom were male. Excessive daytime sleepiness was identified in 25% of the ATC officers, with 84.6% of these based at air traffic control unit A, which has greater air traffic flow, operating a 24-hour alternating work shift schedule. A total of 16% of the ATC officers had stress symptoms, and of these, 62% showed a predominance of physical symptoms. The high percentage of ATC officers with EDS identified in group A may be related to chronodisruption due to night work and alternating shifts.

  7. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  8. The effect of blue-enriched white light on cognitive performances and sleepiness of night-shift workers: A field study.

    Science.gov (United States)

    Motamedzadeh, Majid; Golmohammadi, Rostam; Kazemi, Reza; Heidarimoghadam, Rashid

    2017-08-01

    Night-shift works are basically accompanied by reduced cognitive performance, sleepiness, and higher possibility for human error and related incidents. It is therefore crucial to improve individuals' performance and alertness in sensitive places like industries' control room with the ultimate goal of increasing efficiency and reducing the number of possible incidents. Previous research has indicated that blue light is a critical cue for entraining circadian rhythm. As a result, the present study was an attempt to investigate whether blue-enriched white light illumination was a practical strategy to decrease sleepiness and improve cognitive performance during night shifts. The study, which adopted a before-after interventional design, was conducted among 30 control room staff members of petrochemical industry. After baseline assessments under existing lighting conditions, every participant was exposed to two new lighting conditions (namely, 17,000K and 6500K blue-enriched white light), each lasting for a week. Assessments were conducted again at the end of these treatments. In order to measure the subjective sleepiness, Karolinska Sleepiness Scale (KSS) was utilized. Subjects also performed the Conners' Continuous Performance Test II (CPT-II) and 1-back test in order to gauge their cognitive performance, and melatonin assessment was carried out using salivary and Eliza technique. The data was analyzed using two-way repeated measure ANOVA. The results indicated that, compared to normal lighting conditions, participants' sleepiness and melatonin rhythm significantly declined when they were exposed to blue-enriched white light. Furthermore, the experimental condition had a significant effect on the reduction of working memory errors. It also decreased omission errors and the reaction time during the sustained attention task. Thus, using blue-enriched white light may be a proper ergonomic strategy for improving performance and alertness, especially during night, in

  9. Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

    Science.gov (United States)

    Potenza, Marc N; Hong, Kwang-ik Adam; Lacadie, Cheryl M; Fulbright, Robert K; Tuit, Keri L; Sinha, Rajita

    2012-04-01

    Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

  10. A survey study of the association between mobile phone use and daytime sleepiness in California high school students.

    Science.gov (United States)

    Nathan, Nila; Zeitzer, Jamie

    2013-09-12

    Mobile phone use is near ubiquitous in teenagers. Paralleling the rise in mobile phone use is an equally rapid decline in the amount of time teenagers are spending asleep at night. Prior research indicates that there might be a relationship between daytime sleepiness and nocturnal mobile phone use in teenagers in a variety of countries. As such, the aim of this study was to see if there was an association between mobile phone use, especially at night, and sleepiness in a group of U.S. teenagers. A questionnaire containing an Epworth Sleepiness Scale (ESS) modified for use in teens and questions about qualitative and quantitative use of the mobile phone was completed by students attending Mountain View High School in Mountain View, California (n = 211). Multivariate regression analysis indicated that ESS score was significantly associated with being female, feeling a need to be accessible by mobile phone all of the time, and a past attempt to reduce mobile phone use. The number of daily texts or phone calls was not directly associated with ESS. Those individuals who felt they needed to be accessible and those who had attempted to reduce mobile phone use were also ones who stayed up later to use the mobile phone and were awakened more often at night by the mobile phone. The relationship between daytime sleepiness and mobile phone use was not directly related to the volume of texting but may be related to the temporal pattern of mobile phone use.

  11. Antithyroid Drug-induced Agranulocytosis

    Directory of Open Access Journals (Sweden)

    Ming-Tsung Sun

    2009-08-01

    Full Text Available Antithyroid drugs are widely used to treat hyperthyroidism, especially Graves' disease, but they tend to cause agranulocytosis, which increases the mortality rate. Granulocyte colony-stimulating factor decreases the duration of recovery from agranulocytosis. We retrospectively studied cases of antithyroid drug-induced agranulocytosis over the past 10 years in a northern Taiwan medical center. A clinical evaluation was conducted, including a review of complete blood cell counts and differential counts. Four cases were included in this analysis. Agranulocytosis persisted in 2 cases despite a change in therapy from propylthiouracil to methimazole. Fever, sore throat, and diarrhea were common symptoms of agranulocytosis. Initial white blood cell counts ranged from 450 to 1,710/μL. Only 1 case had a positive result from a throat swab culture (Staphylococcus aureus. Three of 4 cases received granulocyte colony-stimulating factor therapy, and the recovery time ranged from 3 to 13 days. All of the patients recovered from agranulocytosis. We concluded that: (1 conducting a routine complete blood cell count is beneficial in alerting caregivers to the possibility of agranulocytosis; (2 educating patients about the common symptoms of agranulocytosis may contribute to an early diagnosis; (3 providing granulocyte colony-stimulating factor therapy to patients results in good prognosis; and (4 monitoring for cross-reactions between drugs should be performed to prevent further episodes of agranulocytosis.

  12. Drug: D03731 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ric agent ... DG01568 ... MAO inhibitor ... DG01512 ... Monoamine oxidase B inhibitor ... DG01967 ... Antiparkinson agent Cyp... substrate ... DG01644 ... CYP2D6 substrate ... DG01633 ... CYP3A substrate Same as: C07245 ATC code: N04BD01 Chemical group: DG00864 ... Antiparki...nsonian in combination with levodopa/carbidopa MAOB [HSA

  13. Acute fulminant drug induced necrotizing pancreatitis in a patient with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Pablo Miramontes

    2015-03-01

    Full Text Available Drug-induced acute necrotizing pancreatitis is a rare adverse event, although it has been reported in association with different drugs, including non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and analgesic agents commonly used in rheumatology. In different reviews of the pancreotoxicity of drugs, infliximab and etanercept are mentioned among all medications implicated in drug-induced pancreatitis, but clinical cases of acute pancreatitis complicating treatment with these anti-TNF-α agents have been exceptionally reported. We describe a patient with ankylosing spondylitis treated with etanercept, who developed an acute fulminant necrotizing pancreatitis that resulted in death. Doctors should pay close attention to patients taking biologic drugs in which a complaint of abdominal pain lasting for several days with no apparent cause may require a prompt referral for medical consultation.

  14. Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance

    Science.gov (United States)

    Pejovic, Slobodanka; Basta, Maria; Kritikou, Ilia; Shaffer, Michele L.; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O.; Chrousos, George P.

    2013-01-01

    One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown. PMID:23941878

  15. Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance.

    Science.gov (United States)

    Pejovic, Slobodanka; Basta, Maria; Vgontzas, Alexandros N; Kritikou, Ilia; Shaffer, Michele L; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O; Chrousos, George P

    2013-10-01

    One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

  16. Validation of a modified Hindi version of the Epworth Sleepiness Scale among a North Indian population

    Directory of Open Access Journals (Sweden)

    Geetika Bajpai

    2016-01-01

    Full Text Available Background: Since a majority of population in India does not drive automobiles, one item on the Epworth Sleepiness Scale (ESS requires modification and validation. In addition, data collected by us indicated that a majority of rural and urban Indians regularly spend time in prayer/spiritual activity. The main purpose of this study was to develop a cross-cultural adaptation of the ESS for a North Indian population, in Hindi language (ESS-I. The study also provides evidence of reliability and validity of the modified version. Methodology: The subjects included were normal volunteers aged 18-75 years (Group 1 (n = 70, compared with patients with complaints of excessive daytime sleepiness, who had undergone polysomnography (Group 2 (n = 22 and patients who had undergone multiple sleep latency test (Group 3 (n = 10. The study was carried out in four phases: Translation and retranslation of the original scale with modification of item 8 (mainly addition of option of question on "while offering prayers or in spiritual activity"; reliability (test-retest (n = 30; internal consistency (using Cronbach′s alpha index (n = 102; and sensitivity to change (n = 8. Results: Group 1 showed spiritual activity as a significantly more commonly practiced activity than driving. The Cronbach′s alpha for the modified version was 0.892 (excellent, and this was not improved by removing the modified item. The alpha value for Group 1 versus Groups 2 and 3 was 0.667 and 0.892, respectively. The scale was reliable over time (test-retest, and it was sensitive to sleepiness change in patients with obstructive sleep apnea during treatment. Conclusion: The ESS-I, is comparable to the original scale. It is reliable, valid, and change-sensitive. It is proposed that the modified version can be very useful for detecting sleepiness among Indian population, especially those who do not drive their own vehicles.

  17. Effects of armodafinil and cognitive behavior therapy for insomnia on sleep continuity and daytime sleepiness in cancer survivors.

    Science.gov (United States)

    Garland, Sheila N; Roscoe, Joseph A; Heckler, Charles E; Barilla, Holly; Gehrman, Philip; Findley, James C; Peoples, Anita R; Morrow, Gary R; Kamen, Charles; Perlis, Michael L

    2016-04-01

    This study involves the analysis of a secondary outcome of a trial examining whether cognitive behavior therapy for insomnia (CBT-I), a wake-promoting medication (armodafinil), or both results in greater improvement in prospectively assessed sleep continuity and daytime sleepiness than a placebo-alone group among a heterogeneous group of cancer survivors. Whether or not armodafinil alone, and/or when combined with CBT-I, affected adherence with CBT-I was evaluated. This study is a randomized, placebo-controlled, clinical trial. This study was conducted at two northeastern academic medical centers. Eighty-eight cancer survivors with chronic insomnia were recruited between October 2008 and November 2012. Participants were assigned to one of four conditions: 1) CBT-I and placebo (CBT-I+P); 2) CBT-I and armodafinil (CBT-I + A); 2) armodafinil alone (ARM); or 4) placebo alone (PLA). CBT-I was delivered in seven weekly individual therapy sessions (three in person, four via telephone). The armodafinil dosage was 50 mg BID. Sleep continuity was measured with daily sleep diaries assessing sleep latency (SL), wake after sleep onset (WASO), and total sleep time (TST). The Epworth Sleepiness Scale (ESS) measured daytime sleepiness. Compared to the PLA group, the CBT-I+P and CBT-I+A groups reported a significant reduction in SL with effect sizes of 0.67 and 0.58, respectively. A significant reduction was observed in WASO in the CBT-I+A group with an effect size of 0.64. An increasing trend of TST was observed in the CBT-I+P, CBT-I+A, and PLA groups, but not in the ARM group. No statistically significant reductions in daytime sleepiness (ESS) were observed for any of the groups. CBT-I alone and in combination with armodafinil caused significant improvement in sleep continuity. The addition of armodafinil did not appear to improve daytime sleepiness or enhance adherence to CBT-I. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  19. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    International Nuclear Information System (INIS)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-01-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  20. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Devarbhavi, Harshad; Andrade, Raúl J

    2014-05-01

    Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. The Differential Effects of Regular Shift Work and Obstructive Sleep Apnea on Sleepiness, Mood and Neurocognitive Function.

    Science.gov (United States)

    Cori, Jennifer M; Jackson, Melinda L; Barnes, Maree; Westlake, Justine; Emerson, Paul; Lee, Jacen; Galante, Rosa; Hayley, Amie; Wilsmore, Nicholas; Kennedy, Gerard A; Howard, Mark

    2018-05-29

    To assess whether poor sleep quality experienced by regular shift workers and individuals with obstructive sleep apnea (OSA) affects neurobehavioral function similarly, or whether the different aetiologies have distinct patterns of impairment. 37 shift workers (> 24 hours after their last shift), 36 untreated patients with OSA and 39 healthy controls underwent assessment of sleepiness (Epworth Sleepiness Scale [ESS], Oxford Sleep Resistance Test), mood (Beck Depression Index, State Trait Anxiety Inventory [STAI], Profile of Mood States), vigilance (Psychomotor Vigilance Task [PVT], AusEd driving simulation), neurocognitive function (Logical Memory, Trails Making Task, Digit Span and Victoria Stroop Test) and polysomnography. There were no significant differences between the groups in respect to sleepiness (ESS score [median, IQR] = 10.5, 6.3-14 versus 7, 5-11.5 for OSA group and shift work group, respectively) or mood, with the exception of state anxiety which was elevated in the OSA group (STAI score [median, IQR] = 35, 29-43 versus 30, 24-33.5 for OSA group and shift work group, respectively). However, the OSA group performed significantly worse than the shift work group on the driving task (crash proportion = 46.9% versus 18.9% for OSA group and shift work group, respectively) and the PVT (lapses [median, IQR] = 3, 2-6 versus 2, 0-3.5 for OSA group and shift work group, respectively), as well as most of the neurocognitive measures. Participants with OSA had similar sleepiness and mood to the shift work group, but worse vigilance and neurocognitive function. These findings suggest that distinct causes of sleep disturbance likely result in different patterns of neurobehavioral dysfunction. Copyright © 2018 American Academy of Sleep Medicine. All rights reserved.

  2. Associations of Caffeinated Beverage Consumption and Screen Time with Excessive Daytime Sleepiness in Korean High School Students.

    Science.gov (United States)

    Jun, Nuri; Lee, Aeri; Baik, Inkyung

    2017-01-01

    The present study investigated caffeinated beverage consumption and screen time in the association with excessive daytime sleepiness (EDS) and sleep duration. We conducted a cross-sectional study including 249 Korean male high school students. These participants responded to a questionnaire inquiring the information on lifestyle factors, consumption of caffeinated beverages, time spent for screen media, and sleep duration as well as to the Epworth Sleepiness Scale (ESS) questionnaire. EDS was defined as ESS scores of 9 or greater. Students with EDS consumed greater amount of chocolate/cocoa drinks and spent longer time for a TV and a mobile phone than those without EDS (p students with short sleep (≤ 6 hours) consumed greater amount of coffee than others whereas students with long sleep (> 8 hours) consumed greater amount of chocolate/cocoa drinks than others (p sleep duration. Although these findings do not support causal relationships, they suggest that screen time is associated with EDS, but not with sleep duration, and that consumption of certain types of caffeinated beverages is associated with EDS and sleep duration. Adolescents may need to reduce screen time and caffeine consumption to improve sleep quality and avoid daytime sleepiness.

  3. Effects of napping on sleepiness and sleep-related performance deficits in night-shift workers: a systematic review.

    Science.gov (United States)

    Ruggiero, Jeanne S; Redeker, Nancy S

    2014-04-01

    Night-shift workers are prone to sleep deprivation, misalignment of circadian rhythms, and subsequent sleepiness and sleep-related performance deficits. The purpose of this narrative systematic review is to critically review and synthesize the scientific literature regarding improvements in sleepiness and sleep-related performance deficits following planned naps taken during work-shift hours by night workers and to recommend directions for future research and practice. We conducted a literature search using the Medline, PsychInfo, CINAHL, Cochrane Library, and Health and Safety Science Abstracts databases and included English-language quasi-experimental and experimental studies that evaluated the effects of a nighttime nap taken during a simulated or actual night-work shift. We identified 13 relevant studies, which consisted primarily of small samples and mixed designs. Most investigators found that, despite short periods of sleep inertia immediately following naps, night-shift napping led to decreased sleepiness and improved sleep-related performance. None of the studies examined the effects of naps on safety outcomes in the workplace. Larger-scale randomized clinical trials of night-shift napping and direct safety outcomes are needed prior to wider implementation.

  4. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

    Science.gov (United States)

    Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

    2016-01-01

    Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

  5. A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

    Science.gov (United States)

    Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

    2014-08-01

    Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Tóth, S.; Koós, M. [Research Institute for Solid State Physics and Optics, Budapest (Hungary); Beiler, B. [Institute of Isotopes, HAS, Budapest (Hungary)

    2009-07-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)

  7. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Tóth, S.; Koós, M.; Beiler, B.

    2009-01-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)

  8. Sleep Disruption and Daytime Sleepiness Correlating with Disease Severity and Insulin Resistance in Non-Alcoholic Fatty Liver Disease: A Comparison with Healthy Controls.

    Science.gov (United States)

    Bernsmeier, Christine; Weisskopf, Diego M; Pflueger, Marlon O; Mosimann, Jan; Campana, Benedetta; Terracciano, Luigi; Beglinger, Christoph; Heim, Markus H; Cajochen, Christian

    2015-01-01

    Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD. Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters. In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019). In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.

  9. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds

    Directory of Open Access Journals (Sweden)

    Mengxuan Gao

    2017-02-01

    Full Text Available Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.

  10. Circadian rhythms in effects of hypnotics and sleep inducers.

    Science.gov (United States)

    Reinberg, A

    1986-01-01

    Chronopharmacology involves the investigation of drug effects as a function of biological time and the investigation of drug effects on rhythm characteristics. Three new concepts must be considered: (a) the chronokinetics of a drug, embracing rhythmic (circadian) changes in drug bioavailability (or pharmacokinetics) and its excretion (urinary among others); (b) the chronaesthesia of a biosystem to a drug, i.e. circadian changes in the susceptibility of any biosystem to a drug (including organ systems, parasites, etc.); skin and bronchial chronaesthesia to various agents have been documented in man; and (c) the chronergy of a drug, taking into consideration its chronokinetics and the chronaesthesia of the involved organismic biosystems. The term chronergy includes rhythmic changes in the overall effects and in the effectiveness of some drugs. Clinical chronopharmacology is useful for solving problems of drug optimization, i.e. enhancing the desired efficiency of a drug and reducing its undesired effects. Circadian rhythms can be demonstrated in various effects of drugs on sleep, anaesthesia and related processes. For example, in the rat the duration of sleep induced by substances such as pentobarbital, hexobarbital, Althesin (alphaxadone and alphadoline in castor oil) is circadian system stage-dependent. Time-dependent changes of liver enzymes (e.g. hexobarbital oxidase) play a role in these circadian rhythms. The clinical chronopharmacokinetics of benzodiazepines have been documented in man. Chronopharmacologic methods can be used to study desired and undesired hypnotic effects of substances. Such is the case of new antihistamines (anti-H1), which do not induce sleepiness, in either acute or chronic administration. Pertinent also is the problem of intolerance to shift-work. Intolerant shift-workers are subject to internal desynchronization between at least two rhythms (e.g. activity-rest cycle and body temperature). Clinically these workers suffer from sleep

  11. Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

    Science.gov (United States)

    Ishimaru, Naoto; Ohnishi, Hisashi; Nishiuma, Teruaki; Doukuni, Ryota; Umezawa, Kanoko; Oozone, Sachiko; Kuramoto, Emi; Yoshimura, Sho; Kinami, Saori

    2013-01-01

    Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

  12. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

    Science.gov (United States)

    Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard

    2017-01-01

    Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening

  13. Self-reported exposure to traffic pollution in relation to daytime sleepiness and habitual snoring: a questionnaire study in seven North-European cities.

    Science.gov (United States)

    Gislason, Thorarinn; Bertelsen, Randi J; Real, Francisco Gomez; Sigsgaard, Torben; Franklin, Karl A; Lindberg, Eva; Janson, Christer; Arnardottir, Erna Sif; Hellgren, Johan; Benediktsdottir, Bryndis; Forsberg, Bertil; Johannessen, Ane

    2016-08-01

    Little is known about associations between traffic exposure and sleep disturbances. We examined if self-reported exposure to traffic is associated with habitual snoring and daytime sleepiness in a general population. In the RHINE III study, 12184 adults answered questions on sleep disturbances and traffic exposure. We analysed bedrooms near roads with traffic, bedrooms with traffic noise, and travelling regularly along busy roads as proxies for traffic exposures, using logistic regression. Adjustment factors were study centre, gender, age, smoking habits, educational level, body mass index, physical activity, obstructive sleep apnoea, and sleep duration. One in ten lived near a busy road, 6% slept in a bedroom with traffic noise, and 11% travelled regularly along busy roads. Habitual snoring affected 25% and daytime sleepiness 21%. More men reported snoring and more women reported daytime sleepiness. Having a bedroom with traffic noise was associated with snoring (adjusted OR 1.29, [95% CI 1.12, 1.48]). For daytime sleepiness, on the other hand, bedroom with traffic noise and high exposure to traffic pollution have significant risk factors (adjusted ORs 1.46 [1.11, 1.92] and 1.65 [1.11, 2.45]). Results were consistent across study centres. Daytime sleepiness is associated with traffic pollution and traffic noise, while habitual snoring is only associated with traffic noise. Self-reported traffic exposure should be taken into account when diagnosing and planning treatment for patients with sleep disturbances, because reducing noise and pollution exposure in the bedroom may have a beneficial effect. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Symptomatic endometriosis of the posterior cul-de-sac is associated with impaired sleep quality, excessive daytime sleepiness and insomnia: a case-control study.

    Science.gov (United States)

    Leone Roberti Maggiore, Umberto; Bizzarri, Nicolò; Scala, Carolina; Tafi, Emanuela; Siesto, Gabriele; Alessandri, Franco; Ferrero, Simone

    2017-02-01

    To assess the impact of endometriosis of the posterior cul-de-sac on quality of sleep, average daytime sleepiness and insomnia. This age-matched case-control study was conducted in a tertiary referral centre for the diagnosis and treatment of endometriosis between May 2012 and December 2013. It included 145 women with endometriosis of the posterior cul-de-sac (cases; group E) and 145 patients referred to our Institution because of routine gynaecologic consultations (controls; group C). This study investigated whether sleep is impaired in patients with endometriosis of the posterior cul-de-sac. Sleep quality, daytime sleepiness and insomnia were assessed using the following self-administered questionnaires: the Pittsburgh Sleep Quality Index, the Epworth sleepiness scale and the Insomnia Severity Index, respectively. The primary objective of the study was to evaluate sleep quality in the two study groups. Secondary outcomes of the study were to assess average daytime sleepiness and insomnia in the two study groups. The prevalence of poor sleep quality was significantly higher in group E (64.8%) than in group C (15.1%; pinsomnia (29.0%) and moderate clinical insomnia (16.6%) significantly more frequently than patients in group C (24.4% and 5.0%; p=0.002). A substantial proportion of women with endometriosis of the posterior cul-de-sac experiences poor sleep quality, excessive daytime sleepiness and insomnia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Validated Measures of Insomnia, Function, Sleepiness, and Nasal Obstruction in a CPAP Alternatives Clinic Population.

    Science.gov (United States)

    Lam, Austin S; Collop, Nancy A; Bliwise, Donald L; Dedhia, Raj C

    2017-08-15

    Although efficacious in the treatment of obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) can be difficult to tolerate, with long-term adherence rates approaching 50%. CPAP alternatives clinics specialize in the evaluation and treatment of CPAP-intolerant patients; yet this population has not been studied in the literature. To better understand these patients, we sought to assess insomnia, sleep-related functional status, sleepiness, and nasal obstruction, utilizing data from validated instruments. After approval from the Emory University Institutional Review Board, a retrospective chart review was performed from September 2015 to September 2016 of new patient visits at the Emory CPAP alternatives clinic. Patient demographics and responses were recorded from the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), Epworth Sleepiness Scale, and Nasal Obstruction Symptom Evaluation questionnaires. A total of 172 patients were included, with 81% having moderate-severe OSA. Most of the patients demonstrated moderate-severe clinical insomnia and at least moderate nasal obstruction. FOSQ-10 scores indicated sleep-related functional impairment in 88%. However, most patients did not demonstrate excessive daytime sleepiness. This patient population demonstrates significant symptomatology and functional impairment. Because of the severity of their OSA, they are at increased risk of complications. In order to mitigate the detrimental effects of OSA, these significantly impacted patients should be identified and encouraged to seek CPAP alternatives clinics that specialize in the treatment of this population. © 2017 American Academy of Sleep Medicine

  16. Normative data on the diurnal pattern of the Karolinska Sleepiness Scale ratings and its relation to age, sex, work, stress, sleep quality and sickness absence/illness in a large sample of daytime workers.

    Science.gov (United States)

    Åkerstedt, Torbjorn; Hallvig, David; Kecklund, Göran

    2017-10-01

    Self-rated sleepiness responds to sleep loss, time of day and work schedules. There is, however, a lack of a normative reference showing the diurnal pattern during a normal working day, compared with a day off, as well as differences depending on stress, sleep quality, sex, age and being sick listed. The present study sought to provide such data for the Karolinska Sleepiness Scale. Participants were 431 individuals working in medium-sized public service units. Sleepiness (Karolinska Sleepiness Scale, scale 1-9) was rated at six times a day for a working week and 2 days off (>90.000 ratings). The results show a clear circadian pattern, with high values during the morning (4.5 at 07:00 hours) and evening (6.0 at 22:00 hours), and with low values (3-4) during the 10:00-16:00 hours span. Women had significantly higher (0.5 units) Karolinska Sleepiness Scale values than men, as did younger individuals (0.3 units), those with stress (1.3 units above the low-stress group) and those with poor sleep quality (1.0 units above those with qood sleep quality). Days off showed reduced sleepiness (0.7 units), while being sick listed was associated with an increased sleepiness (0.8 units). Multiple regression analysis of mean sleepiness during the working week yielded mean daytime stress, mean sleep quality, age, and sex as predictors (not sleep duration). Improved sleep quality accounted for the reduced sleepiness during days off, but reduced stress was a second factor. Similar results were obtained in a longitudinal mixed-model regression analysis across the 7 days of the week. The percentage of ratings at Karolinska Sleepiness Scale risk levels (8 + 9) was 6.6%, but most of these were obtained at 22:00 hours. It was concluded that sleepiness ratings are strongly associated with time of day, sleep quality, stress, work day/day off, being ill, age, and sex. © 2017 European Sleep Research Society.

  17. Drug induced hypertension--An unappreciated cause of secondary hypertension.

    Science.gov (United States)

    Grossman, Alon; Messerli, Franz H; Grossman, Ehud

    2015-09-15

    Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Immunoexpression of interleukin-6 in drug-induced gingival overgrowth patients

    Directory of Open Access Journals (Sweden)

    P R Ganesh

    2016-01-01

    Full Text Available Background: To analyze the role of proinflammatory cytokines in drug-induced gingival enlargement in Indian population. Aim: To evaluate for the presence of interleukin-6 (IL-6 in drug-induced gingival enlargement and to compare it with healthy control in the absence of enlargement. Materials and Methods: Thirty-five patients selected for the study and divided into control group (10 and study group (25 consisting of phenytoin (10; cyclosporin (10 and nifedipine (5 induced gingival enlargement. Gingival overgrowth index of Seymour was used to assess overgrowth and allot groups. Under LA, incisional biopsy done, tissue sample fixed in 10% formalin and immunohistochemically evaluated for the presence of IL-6 using LAB-SA method, Labeled- Streptavidin-Biotin Method (LAB-SA kit from Zymed- 2nd generation LAB-SA detection system, Zymed Laboratories, CA. The results of immunohistochemistry were statistically analyzed using Kruskaal–Wallis and Mann–Whitney test. Results: The data obtained from immunohistochemistry assessment shows that drug-induced gingival overgrowth (DIGO samples express more IL-6 than control group and cyclosporin expresses more IL-6 followed by phenytoin and nifedipine. Conclusion: Increased IL-6 expression was noticed in all three DIGO groups in comparison with control group. Among the study group, cyclosporin expressed maximum IL-6 expression followed by phenytoin and nifedipine.

  19. Gamma-sterilization-induced radicals in biodegradable drug delivery systems

    International Nuclear Information System (INIS)

    Maeder, K.; Swartz, H.M.; Domb, A.

    1996-01-01

    Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 o C) was used to characterize free radicals in gamma-ray sterilized biodegradable polymers of the type which are in clinical use. Free radicals were detected in all irradiated polymer samples. The temperature of irradiation (25 o vs dry ice temperature) had only a minor influence on the yield of radicals and the shape of the EPR spectra. In contrast, the composition of the polymers and the drugs incorporated in them did strongly influence the amount of radiation-induced free radicals and their reactivity. In general, polymers with high melting points and crystallinity had the highest yields of radicals observable at room temperature. We were able to use the free radicals induced by the usual sterilization procedures to follow the penetration of water and the degradation of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug delivery noninvasively and continuously in vivo, using the free radicals induced in the usual sterilization process indicates that this approach could be applied immediately for the characterization of these drug delivery systems in experimental animals and in the near future should be able to be used in human subjects. (author)

  20. Drug-Induced Vasculitis: New Insights and a Changing Lineup of Suspects.

    Science.gov (United States)

    Grau, Rafael G

    2015-12-01

    An increasing number of therapeutic agents have been associated with a vasculitic syndrome. This usually involves small vessels, primarily capillaries, venules, and arterioles in leukocytoclastic vasculitis, small-vessel disease similar to an antineutrophil cytoplasmic antibody-related vasculitis, or mid-sized muscular arteries in a polyarteritis-like picture. Antineutrophil cytoplasmic antibodies are present in many cases of vasculitis regardless of the size of the vessel involved. Monoclonal antibodies used to treat many autoimmune disorders have become the most common agents associated with drug-induced vasculitis. Important advances in epigenetics, genetics, and neutrophil apoptosis are providing new insights into the pathogenesis of both drug-induced vasculitis and idiopathic vasculitis. Although management has not changed significantly in the past few years where withdrawal of the offending agent is the primary intervention, increasing awareness of drug-induced vasculitis can lead to earlier diagnosis and prevention of severe organ damage and fatalities.

  1. Parents of children referred to a sleep laboratory for disordered breathing reported anxiety, daytime sleepiness and poor sleep quality.

    Science.gov (United States)

    Cadart, Marion; De Sanctis, Livio; Khirani, Sonia; Amaddeo, Alessandro; Ouss, Lisa; Fauroux, Brigitte

    2018-07-01

    We evaluated the impact that having a child with sleep-disordered breathing had on their parents, including their own sleep quality. Questionnaires were completed by 96 parents of 86 children referred for a sleep study or control of continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) at the sleep laboratory of the Necker Hospital, Paris, France, between October 2015 and January 2016. The questionnaires evaluated anxiety and depression, family functioning, the parents' quality of life, daytime sleepiness and sleep quality. The children had a mean age of seven ±five years and most of the responses (79%) came from their mothers. These showed that 26% of parents showed moderate-to-severe anxiety, 8% moderate-to-severe depression, 6% complex family cohesion, 59% moderate-to-severe daytime sleepiness and 54% poor sleep quality. Anxiety was higher in mothers than in fathers (p parents of children referred to a sleep laboratory reported frequent anxiety, daytime sleepiness and poor sleep quality. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  2. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Tolosa, Laia [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Gómez-Lechón, M. José [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Jiménez, Nuria [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Hervás, David [Biostatistics Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Jover, Ramiro [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain); Donato, M. Teresa, E-mail: donato_mte@gva.es [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain)

    2016-07-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  3. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    International Nuclear Information System (INIS)

    Tolosa, Laia; Gómez-Lechón, M. José; Jiménez, Nuria; Hervás, David; Jover, Ramiro; Donato, M. Teresa

    2016-01-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  4. The association between use of electronic media in bed before going to sleep and insomnia symptoms, daytime sleepiness, morningness, and chronotype.

    Science.gov (United States)

    Fossum, Ingrid Nesdal; Nordnes, Linn Tinnesand; Storemark, Sunniva Straume; Bjorvatn, Bjørn; Pallesen, Ståle

    2014-09-03

    This study investigated whether the use of a television, computer, gaming console, tablet, mobile phone, or audio player in bed before going to sleep was associated with insomnia, daytime sleepiness, morningness, or chronotype. 532 students aged 18-39 were recruited from lectures or via e-mail. Respondents reported the frequency and average duration of their in-bed media use, as well as insomnia symptoms, daytime sleepiness, morningness-eveningness preference and bedtime/rise time on days off. Mean time of media use per night was 46.6 minutes. The results showed that computer usage for playing/surfing/reading was positively associated with insomnia, and negatively associated with morningness. Mobile phone usage for playing/surfing/texting was positively associated with insomnia and chronotype, and negatively associated with morningness. None of the other media devices were related to either of these variables, and no type of media use was related to daytime sleepiness.

  5. Excessive daytime sleepiness and body composition: a population-based study of adults.

    Directory of Open Access Journals (Sweden)

    Amie C Hayley

    Full Text Available BACKGROUND: Excessive daytime sleepiness (EDS is often associated with increased adiposity, particularly when assessed in the context of samples of sleep-disordered patients; however, it is unclear if this relationship is sustained among non-clinical, population-based cohorts. This study aimed to investigate the relationship between EDS and a number of body composition markers among a population-based sample of men and women. METHODS: This study assessed 1066 women aged 21-94 yr (median = 51 yr, IQR 35-66, and 911 men aged 24-92 yr (median = 60 yr, IQR 46-73 who participated in the Geelong Osteoporosis Study (GOS between the years 2001 and 2008. Total body fat mass was determined from whole body dual-energy X-ray absorptiometry scans, and anthropometric parameters (weight, height, and waist circumference were measured. Lifestyle and health information was collected via self-report. Sleepiness was assessed using the Epworth Sleepiness Scale (ESS. Scores of ≥ 10 were considered indicative of EDS. RESULTS: Women: After adjusting for age, alcohol intake, antidepressant medication use and physical activity, EDS was associated with greater waist circumference and body mass index (BMI. EDS was also associated with 1.5-1.6-fold increased odds of being overweight or obese. Men: After adjusting for age, alcohol use, physical activity and smoking status, EDS was associated with greater BMI. These findings were not explained by the use of sedative or antidepressant medication. EDS was also associated with 1.5-fold increased likelihood of being obese, independent of these factors. No differences in lean mass, %body fat, or %lean mass were detected between those with and without EDS for men or women. CONCLUSIONS: These data suggest that EDS is associated with several anthropometric adiposity profiles, independent of associated lifestyle and health factors. Among women, symptoms of EDS are pervasive at both overweight and obese BMI classifications

  6. Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia

    Directory of Open Access Journals (Sweden)

    Angeliki Tsapanou

    2015-07-01

    Full Text Available Background/Aims: To examine the association between self-reported sleep problems and incidence of dementia in community-dwelling elderly people. Methods: 1,041 nondemented participants over 65 years old were examined longitudinally. Sleep problems were estimated using the RAND Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, sleep short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and risk for incident dementia. Age, gender, education, ethnicity, APOE-ε4, stroke, heart disease, hypertension, diabetes, and depression were included as covariates. Results: Over 3 years of follow-up, 966 (92.8% participants remained nondemented, while 78 (7.2% developed dementia. In unadjusted models, sleep inadequacy (‘Get the amount of sleep you need' at the initial visit was associated with increased risk of incident dementia (HR = 1.20; 95% CI 1.02-1.42; p = 0.027. Adjusting for all the covariates, increased risk of incident dementia was still associated with sleep inadequacy (HR = 1.20; 95% CI 1.01-1.42; p = 0.040, as well as with increased daytime sleepiness (‘Have trouble staying awake during the day' (HR = 1.24; 95% CI 1.00-1.54; p = 0.047. Conclusion: Our results suggest that sleep inadequacy and increased daytime sleepiness are risk factors for dementia in older adults, independent of demographic and clinical factors.

  7. Antithyroid drug-induced fetal goitrous hypothyroidism

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Rasmussen, Ase Krogh; Sundberg, Karin

    2011-01-01

    Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can...... be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T(4) are the most consistent indication of maternal...... and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T(4) levels....

  8. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

    Directory of Open Access Journals (Sweden)

    Stavrinou Lampis C

    2011-06-01

    Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  9. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

    Science.gov (United States)

    Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

    2011-06-29

    The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  10. Drug-induced lung disease: High-resolution CT and histological findings

    International Nuclear Information System (INIS)

    Cleverley, Joanne R.; Screaton, Nicholas J.; Hiorns, Melanie P.; Flint, Julia D.A.; Mueller, Nestor L.

    2002-01-01

    AIM: To compare the parenchymal high-resolution computed tomography (HRCT) appearances with histological findings in patients with drug-induced lung disease and to determine the prognostic value of HRCT. MATERIALS AND METHODS: Drug history, HRCT features, histological findings and outcome at 3 months in 20 patients with drug induced-lung disease were reviewed retrospectively. The HRCT images were assessed for the pattern and distribution of abnormalities and classified as most suggestive of interstitial pneumonitis/fibrosis, diffuse alveolar damage (DAD), organizing pneumonia (OP) reaction, or a hypersensitivity reaction. RESULTS: On histopathological examination there were eight cases of interstitial pneumonitis/fibrosis, five of DAD, five of OP reactions, one of hypersensitivity reaction and one of pulmonary eosinophilia. The most common abnormalities on HRCT were ground-glass opacities (n = 17), consolidation (n = 14), interlobular septal thickening (n = 15) and centrilobular nodules (n 8). HRCT interpretation and histological diagnosis were concordant in only nine (45%) of 20 patients. The pattern, distribution, and extent of HRCT abnormalities were of limited prognostic value: all eight patients with histological findings of OP, hypersensitivity reaction, or eosinophilic infiltrate improved on follow-up compared to only five of 13 patients with interstitial pneumonitis/fibrosis or DAD. CONCLUSION: In many cases of drug-induced lung injury HRCT is of limited value in determining the histological pattern and prognosis. Cleverly, J.R. et al

  11. Clinical utility of the Chinese version of the Pediatric Daytime Sleepiness Scale in children with obstructive sleep apnea syndrome and narcolepsy.

    Science.gov (United States)

    Yang, Chien-Ming; Huang, Yu-Shu; Song, Yu-Chen

    2010-04-01

    The present study examined the psychometric properties of the Chinese version of the Pediatric Daytime Sleepiness Scale (PDSS) and the utility of the PDSS as a screening tool for pathological daytime sleepiness in teenagers with obstructive sleep apnea (OSA) and narcolepsy. The PDSS was first administered to 238 middle and high school students to assess the reliability of the scale, and then administered to 28 teenagers with OSA, 31 teenagers with narcolepsy, and 34 normal controls to evaluate its clinical utility. Test-retest reliability and internal consistency were acceptable. The PDSS scores were significantly higher in narcoleptic subjects than in subjects with OSA, and higher in OSA syndrome (OSAS) subjects than normal controls. Furthermore, the scores decreased in narcoleptic subjects after medical treatment. Both reliability and validity were proven to be good. As a screening tool for narcolepsy, receiver operator characteristic (ROC) curve analysis showed that the PDSS, with a cut-off score of 16/17, had good sensitivity (87.1%) and fair specificity (74.3%) for identifying individuals with narcolepsy. When used for screening OSA, however, the differentiating power was not as good. The PDSS is a reliable and valid tool for the measurement of sleepiness in clinical youth populations. When used as a screening tool, it is useful for sleep disorders involving more severe pathological sleepiness, as in narcolepsy.

  12. Daytime Sleepiness, Poor Sleep Quality, Eveningness Chronotype, and Common Mental Disorders among Chilean College Students

    Science.gov (United States)

    Concepcion, Tessa; Barbosa, Clarita; Vélez, Juan Carlos; Pepper, Micah; Andrade, Asterio; Gelaye, Bizu; Yanez, David; Williams, Michelle A.

    2014-01-01

    Objectives: To evaluate whether daytime sleepiness, poor sleep quality, and morningness and eveningness preferences are associated with common mental disorders (CMDs) among college students. Methods: A total of 963 college students completed self-administered questionnaires that collected information about sociodemographic characteristics, sleep…

  13. Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study

    OpenAIRE

    Czeisler, Charles A.; Walsh, James K.; Wesnes, Keith A.; Arora, Sanjay; Roth, Thomas

    2009-01-01

    OBJECTIVE: To assess the effect of armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (≥3 months) shift work disorder (SWD) of moderate or greater severity.

  14. Sleep Disruption and Daytime Sleepiness Correlating with Disease Severity and Insulin Resistance in Non-Alcoholic Fatty Liver Disease: A Comparison with Healthy Controls.

    Directory of Open Access Journals (Sweden)

    Christine Bernsmeier

    Full Text Available Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD.Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale, Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters.In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176 and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149. Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074 and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001. In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017] and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009] independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019.In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.

  15. Gender differences in excessive daytime sleepiness among Japanese workers.

    Science.gov (United States)

    Doi, Yuriko; Minowa, Masumi

    2003-02-01

    Excessive daytime sleepiness (EDS) is serious concern in the workplace with respect to errors, accidents, absenteeism, reduced productivity and impaired personal or professional life. Previous community studies found a female preponderance of EDS, however, there is little research on EDS and gender in occupational settings. We examined the gender differences in prevalence and risk factors of EDS among employees working at a telecommunications company in the Tokyo metropolitan area. Our outcome measure of EDS was the Epworth Sleepiness Scale (ESS). A self-administered questionnaire on health and sleep including ESS was distributed to 5,571 workers between December 1999 and January 2000, and 5,072 responses were returned (91.0%). A total of 4,722 full-time, non-manual and non-shift employees aged 20-59 were used for analysis (3,909 men and 813 women). Chi-squared tests and multiple logistic regression analyses were applied for examining the gender differences in the prevalence and risk factors of EDS. The prevalence rates of EDS were 13.3% for women and 7.2% for men (Pgenders, and being married worked as a protective factor against EDS for men alone. It is obvious that a ban on overtime work and a provision of mental health hygiene are the general strategies for reducing EDS at worksites. In the case of women, we suggest the formation of effective strategies for improving women's status at home and in the workplace must also be a solution for the prevention of EDS (e.g. promoting gender equality in the division of labor at home and strengthening family care policies for working women).

  16. Drug-Induced Anaphylaxis in Latin American Countries.

    Science.gov (United States)

    Jares, Edgardo José; Baena-Cagnani, Carlos E; Sánchez-Borges, Mario; Ensina, Luis Felipe C; Arias-Cruz, Alfredo; Gómez, Maximiliano; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos; Monsell, Silvana; Schuhl, Juan; Cardona-Villa, Ricardo

    2015-01-01

    Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P asthma (N = 22 vs 35 [38.6% vs 61.4%], P Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Drug-induced liver injury due to antibiotics.

    Science.gov (United States)

    Björnsson, Einar S

    Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

  18. Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug-induced Liver Injury.

    Science.gov (United States)

    Jing, Jing; Teschke, Rolf

    2018-03-28

    Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly published in the scientific literature worldwide. As opposed to the multiplicity of botanical chemicals in herbal TCM products, which are often mixtures of several herbs, conventional Western drugs contain only a single synthetic chemical. It is therefore of interest to study how HILI by TCM and DILI compare with each other, and to what extent results from each liver injury type can be transferred to the other. China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM. Therefore, China is well suited to studies of liver injury comparing drugs with TCM herbs. Despite some concordance, recent analyses of liver injury cases with verified causality, using the Roussel Uclaf Causality Assessment Method, revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features: HILI cases are less frequently observed as compared to DILI, have a smaller proportion of females and less unintentional rechallenge events, and present a higher rate of hepatocellular injury features. Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs, such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

  19. Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

    NARCIS (Netherlands)

    Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

    2016-01-01

    Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

  20. Drug-induced parkinsonism: diagnosis and management

    Directory of Open Access Journals (Sweden)

    Blanchet PJ

    2016-09-01

    Full Text Available Pierre J Blanchet,1–3 Veronika Kivenko1–3 1Department of Stomatology, Faculty of Dental Medicine, University of Montreal, 2Andre-Barbeau Movement Disorders Unit, University of Montreal Hospital Center (CHU Montreal, 3Montreal Mental Health University Institute, Montreal, QC, Canada Abstract: Drug-induced parkinsonism (DIP has been known for >60 years. It is the second leading cause of parkinsonism, but still underdiagnosis is likely to influence reported incidence figures. Since DIP is clinically undistinguishable from Lewy-body Parkinson’s disease, any new case of parkinsonism should prompt the search for an offending antipsychotic, hidden neuroleptic, or nonneuroleptic agent that may produce DIP. DIP is reversible upon drug withdrawal in most cases. There is no consensus regarding the duration of the recovery period to allow motor signs to fully remit in order to confirm the diagnosis of DIP following removal of the causative agent, but a drug-free interval of at least 6 months is generally recommended. Interestingly, up to 30% of DIP cases may show persisting or worsening motor signs beyond 6 months following drug withdrawal or adjustment, due to complex postsynaptic and presynaptic factors that may variably interact to negatively influence nigrostriatal dopamine transmission in a so-called “double-hit” hypothesis. The condition significantly impacts on quality of life and increases the risks of morbidity and mortality. Management is challenging in psychiatric patients and requires a team approach to achieve the best outcome. Keywords: neuroleptic drugs, extrapyramidal side effects, second generation antipsychotics, calcium channel blockers, valproic acid, tetrabenazine 

  1. Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

    International Nuclear Information System (INIS)

    Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

    2017-01-01

    Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

  2. Individual vulnerability to insomnia, excessive sleepiness and shift work disorder amongst healthcare shift workers. A systematic review.

    Science.gov (United States)

    Booker, Lauren A; Magee, Michelle; Rajaratnam, Shantha M W; Sletten, Tracey L; Howard, Mark E

    2018-03-27

    Shift workers often experience reduced sleep quality, duration and/or excessive sleepiness due to the imposed conflict between work and their circadian system. About 20-30% of shift workers experience prominent insomnia symptoms and excessive daytime sleepiness consistent with the circadian rhythm sleep disorder known as shift work disorder. Individual factors may influence this vulnerability to shift work disorder or sleep-related impairment associated with shift work. This paper was registered with Prospero and was conducted using recommended standards for systematic reviews and meta-analyses. Published literature that measured sleep-related impairment associated with shift work including reduced sleep quality and duration and increased daytime sleepiness amongst healthcare shift workers and explored characteristics associated with individual variability were reviewed. Fifty-eight studies were included. Older age, morning-type, circadian flexibility, being married or having children, increased caffeine intake, higher scores on neuroticism and lower on hardiness were related to a higher risk of sleep-related impairment in response to shift work, whereas physical activity was a protective factor. The review highlights the diverse range of measurement tools used to evaluate the impact of shift work on sleep. Use of standardised and validated tools would enable cross-study comparisons. Longitudinal studies are required to establish causal relationships between individual factors and the development of shift work disorder. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Effects of long working hours and the night shift on severe sleepiness among workers with 12-hour shift systems for 5 to 7 consecutive days in the automobile factories of Korea.

    Science.gov (United States)

    Son, Mia; Kong, Jeong-Ok; Koh, Sang-Baek; Kim, Jaeyoung; Härmä, Mikko

    2008-12-01

    We investigated the effects of 12-hour shift work for five to seven consecutive days and overtime on the prevalence of severe sleepiness in the automobile industry in Korea. [Correction added after online publication 28 Nov: Opening sentence of the summary has been rephrased for better clarity.] A total of 288 randomly selected male workers from two automobile factories were selected and investigated using questionnaires and sleep-wake diaries in South Korea. The prevalence of severe sleepiness at work [i.e. Karolinska Sleepiness Scale (KSS) score of 7 or higher] was modeled using marginal logistic regression and included theoretical risk factors related to working hours and potential confounding factors related to socio-economic status, work demands, and health behaviors. Factors related to working hours increased the risk for severe sleepiness at the end of the shift in the following order: the night shift [odds ratio (OR): 4.7; 95% confidence interval (CI): 3.6-6.0)], daily overtime (OR: 2.2; 95% CI: 1.7-2.9), weekly overtime (OR: 1.6; 95% CI: 1.0-2.6), and night overtime (OR: 1.6; 95% CI: 0.8-3.0). Long working hours and shift work had a significant interactive effect for severe sleepiness at work. Night shift workers who worked for 12 h or more a day were exposed to a risk of severe sleepiness that was 7.5 times greater than day shift workers who worked less than 11 h. Night shifts and long working hours were the main risk factors for severe sleepiness among automobile factory workers in Korea. Night shifts and long working hours have a high degree of interactive effects resulting in severe sleepiness at work, which highlight the need for immediate measures to address these characteristics among South Korean labor force patterns.

  4. Improvement in Fatigue, Sleepiness, and Health-Related Quality of Life with Bright Light Treatment in Persons with Seasonal Affective Disorder and Subsyndromal SAD

    Directory of Open Access Journals (Sweden)

    Cecilia Rastad

    2011-01-01

    Full Text Available Objective. To investigate the effects of bright light treatment for secondary outcome measures and to explore and validate empirically derived subgroups and treatment effects in subgroups. Methods. A descriptive design. A sample of forty-nine persons (mean age of 45.8 with clinically assessed seasonal affective disorder (SAD or subsyndromal SAD (S-SAD participated in a two-group clinical trial evaluating the effects of treatment with bright light therapy. A person-oriented cluster analysis was applied to study treatment effects in subgroups. Results. For the merged group, sleepiness (Epworth Sleepiness Scale, fatigue (fatigue questionnaire, and health-related quality of life (SF-36 were improved at posttreatment, and results were maintained at the one-month followup. Three distinct subgroups had a high level of fatigue in common, while the level of excessive daytime sleepiness and depressed mood differed between the subgroups. Over time, all subgroups improved following ten days treatment in a light room. Conclusion. Fatigue, excessive daytime sleepiness, and health-related quality of life improve in a similar way as depressed mood following treatment with bright light. The treatment was effective irrespective of the severity of the disorder, that is, for persons with SAD and subsyndromal SAD.

  5. Drug-induced gingival enlargement: Series of cases

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    Isabella Manzur-Villalobos

    2018-01-01

    Full Text Available Introduction: Gingival enlargement (GA is a benign condition of the oral cavity that is characterized by the excessive growth of the gingiva in mass and volume. This lesion is not only caused by hereditary factors or poor oral hygiene, but also by the intake of medications, including antihypertensive, anticonvulsant and immunosuppressive drugs. Objective: To sensitize the prevention or early care in patients with pathologies that merit the use of antihypertensive and anticonvulsants in conjunction with the dentist, to treat or avoid the drug-induced gingival enlargement (DIGE. Materials and methods: A series of clinical cases of patients with gingival enlargement by various drugs are reported, including Phenytoin, Amlodipine and Nifedipine. Periodontal and gingivectomy hygienic phase measures were applied to obtain better effects. Results: Satisfactory results were obtained with a considerable decrease in DIGE. Conclusions: The integral management is important in conjunction with the treating physician to follow up the drug that can be generating gingival enlargement. It is necessary to employ an initial approach with strategies of periodontal hygiene, and in severe cases and, as last resort, the periodontal surgery with gingivectomy and gingivoplasty.

  6. Sleep hygiene and its association with daytime sleepiness, depressive symptoms, and quality of life in patients with mild obstructive sleep apnea.

    Science.gov (United States)

    Lee, Sang-Ahm; Paek, Joon-Hyun; Han, Su-Hyun

    2015-12-15

    To investigate the direct and indirect associations of sleep hygiene with daytime sleepiness, depressive symptoms, and quality of life (QoL), in newly diagnosed, untreated patients with mild obstructive sleep apnea (OSA). Data were collected from adults with mild OSA. The Sleep Hygiene Index (SHI), Sleep Problems Index-1 (SPI-1) of the Medical Outcomes Study-Sleep Scale, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Medical Outcomes Study Short-Form Health survey (SF-36) were used to evaluate patients. To determine the indirect and direct associations between SHI and disease outcomes, the Sobel test and multiple linear regression analyses were used, respectively. When we evaluated the direct associations, we excluded 3 items of the original SHI which were more reflective of general health rather than sleep-specific habits and environments. In total, 260 patients with mild OSA participated in this study. The average age, AHI, and SHI scores were 49.1 years (SD 12.5), 9.3/h (SD 2.9), and 24.7 (SD 6.0), respectively. Here, ≥ 10% of participants indicated poor sleep hygiene behaviors on 7 of 13 items. Young age and men were associated with higher SHI scores (both phygiene is indirectly related to daytime sleepiness, depressive symptoms, QoL via sleep quality and also related to daytime sleepiness and QoL independent of sleep quality in mild OSA patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Can we get more from the Epworth Sleepiness Scale (ESS) than just a single score?

    DEFF Research Database (Denmark)

    Olaithe, Michelle; Skinner, Timothy C.; Clarke, Jemma

    2013-01-01

    a person's posture, activity and environment. These features of sleepiness are referred to as somnificity. This study evaluates and compares the fit of a one-factor structure (sleepiness) and three-factor structure (reflecting low, medium and high levels of somnificity) for the ESS. Methods: All...... participants (a community sample N = 356 and a clinical sample N = 679) were administered the ESS. Confirmatory factor analysis was used to evaluate and compare the fit of one- and three-factor models of the ESS. Results: In both samples, a three-factor structure (community sample adjusted X 2 = 2.95, root...... mean square error of approximation (RMSEA) = 0.07, Comparative Fit Index (CFI) = 0.95; clinical sample adjusted X 2 = 3.98, RMSEA = 0.07, CFI = 0.98) provided a level of model fit that was at least as good as the one-factor structure (community sample adjusted X 2 = 5.01, RMSEA = 0.11, CFI = 0...

  8. Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD: A Swedish Register-Based Study.

    Directory of Open Access Journals (Sweden)

    Ylva Haasum

    Full Text Available Many drugs increase the risk of falls in old age. Although persons with Parkinson's disease (PD are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD, compared to persons without APD.We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs.FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12. The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44-1.55.The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD.

  9. Potential candidate genomic biomarkers of drug induced vascular injury in the rat

    International Nuclear Information System (INIS)

    Dalmas, Deidre A.; Scicchitano, Marshall S.; Mullins, David; Hughes-Earle, Angela; Tatsuoka, Kay; Magid-Slav, Michal; Frazier, Kendall S.; Thomas, Heath C.

    2011-01-01

    Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n = 6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. -- Highlights: ► A gene panel was developed to help predict rat drug-induced mesenteric MAN. ► A gene panel was identified following treatment of rats with 28

  10. Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

    International Nuclear Information System (INIS)

    Makin, Guy; Dive, Caroline

    2001-01-01

    Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance

  11. The Open Form Inducer Approach for Structure-Based Drug Design.

    Directory of Open Access Journals (Sweden)

    Daniel Ken Inaoka

    Full Text Available Many open form (OF structures of drug targets were obtained a posteriori by analysis of co-crystals with inhibitors. Therefore, obtaining the OF structure of a drug target a priori will accelerate development of potent inhibitors. In addition to its small active site, Trypanosoma cruzi dihydroorotate dehydrogenase (TcDHODH is fully functional in its monomeric form, making drug design approaches targeting the active site and protein-protein interactions unrealistic. Therefore, a novel a priori approach was developed to determination the TcDHODH active site in OF. This approach consists of generating an "OF inducer" (predicted in silico to bind the target and cause steric repulsion with flexible regions proximal to the active site that force it open. We provide the first proof-of-concept of this approach by predicting and crystallizing TcDHODH in complex with an OF inducer, thereby obtaining the OF a priori with its subsequent use in designing potent and selective inhibitors. Fourteen co-crystal structures of TcDHODH with the designed inhibitors are presented herein. This approach has potential to encourage drug design against diseases where the molecular targets are such difficult proteins possessing small AS volume. This approach can be extended to study open/close conformation of proteins in general, the identification of allosteric pockets and inhibitors for other drug targets where conventional drug design approaches are not applicable, as well as the effective exploitation of the increasing number of protein structures deposited in Protein Data Bank.

  12. Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

    Science.gov (United States)

    Lee, Jeonghwan; Kim, Sejoong

    2018-03-08

    The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Incidence of drug-induced torsades de pointes with intravenous amiodarone

    Directory of Open Access Journals (Sweden)

    Jayaprakash Shenthar

    2017-11-01

    Conclusion: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.

  14. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    International Nuclear Information System (INIS)

    Liu, Cong; Sekine, Shuichi; Ito, Kousei

    2016-01-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  15. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Cong; Sekine, Shuichi, E-mail: ssekine@faculty.chiba-u.jp; Ito, Kousei

    2016-07-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  16. Melatonin modulates drug-induced acute porphyria

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    Sandra M. Lelli

    Full Text Available This work investigated the modulation by melatonin (Mel of the effects of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide (AIA and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC on oxidative environment, glucose biosynthesis and heme pathway parameters. Administration of Mel before rat intoxication with AIA/DDC showed a clear beneficial effect in all cases. Mel induced decreases of 42% and 35% in the excretion of the hemeprecursors 5-aminolevulinic acid (ALA and porphobilinogen (PBG, respectively, and a 33% decrease in the induction of the heme regulatory enzyme 5-aminolevulinic acid-synthase (ALA-S. The activity of the glucose metabolism enzyme phosphoenolpyruvate carboxykinase (PEPCK, which had been diminished by the porphyrinogenic treatment, was restored by 45% when animals were pre-treated with Mel. Mel abolished the modest decrease in glucose 6-phospatase (G6Pase activity caused by AIA/DDC treatment. The oxidative status of lipids was attenuated by Mel treatment in homogenates by 47%, whereas no statistically significant AIA/DDC-induced increase in thiobarbituric acid reactive substances (TBARS was observed in microsomes after Mel pre-treatment. We hypothesize that Mel may be scavenging reactive species of oxygen (ROS that could be damaging lipids, PEPCK, G6Pase and ferrochelatase (FQ. Additionally, Mel administration resulted in the repression of the key enzyme ALA-S, and this could be due to an increase in glucose levels, which is known to inhibit ALA-S induction. The consequent decrease in levels of the heme precursors ALA and PBG had a beneficial effect on the drug-induced porphyria. The results obtained open the possibility of further research on the use of melatonin as a co-treatment option in acute porphyria. Keywords: Melatonin, Glucose synthesis, Heme pathway, Acute porphyria, Oxidative stress

  17. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis

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    Zenya Saito

    2016-11-01

    Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

  18. Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis

    Science.gov (United States)

    Saito, Kosuke; Maekawa, Keiko; Ishikawa, Masaki; Senoo, Yuya; Urata, Masayo; Murayama, Mayumi; Nakatsu, Noriyuki; Yamada, Hiroshi; Saito, Yoshiro

    2014-01-01

    Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis. PMID:24980264

  19. An Efficient Sleepy Algorithm for Particle-Based Fluids

    Directory of Open Access Journals (Sweden)

    Xiao Nie

    2014-01-01

    Full Text Available We present a novel Smoothed Particle Hydrodynamics (SPH based algorithm for efficiently simulating compressible and weakly compressible particle fluids. Prior particle-based methods simulate all fluid particles; however, in many cases some particles appearing to be at rest can be safely ignored without notably affecting the fluid flow behavior. To identify these particles, a novel sleepy strategy is introduced. By utilizing this strategy, only a portion of the fluid particles requires computational resources; thus an obvious performance gain can be achieved. In addition, in order to resolve unphysical clumping issue due to tensile instability in SPH based methods, a new artificial repulsive force is provided. We demonstrate that our approach can be easily integrated with existing SPH based methods to improve the efficiency without sacrificing visual quality.

  20. Trends in insomnia and excessive daytime sleepiness among U.S. adults from 2002 to 2012.

    Science.gov (United States)

    Ford, Earl S; Cunningham, Timothy J; Giles, Wayne H; Croft, Janet B

    2015-03-01

    Insomnia is a prevalent disorder in the United States and elsewhere. It has been associated with a range of somatic and psychiatric conditions, and adversely affects quality of life, productivity at work, and school performance. The objective of this study was to examine the trend in self-reported insomnia and excessive daytime sleepiness among US adults. We used data of participants aged ≥18 years from the National Health Interview Survey for the years 2002 (30,970 participants), 2007 (23,344 participants), and 2012 (34,509 participants). The unadjusted prevalence of insomnia or trouble sleeping increased from 17.5% (representing 37.5 million adults) in 2002 to 19.2% (representing 46.2 million adults) in 2012 (relative increase: +8.0%) (P trend increased from 17.4% to 18.8%. Significant increases were present among participants aged 18-24, 25-34, 55-64, and 65-74 years, men, women, whites, Hispanics, participants with diabetes, and participants with joint pain. Large relative increases occurred among participants aged 18-24 years (+30.9%) and participants with diabetes (+27.0%). The age-adjusted percentage of participants who reported regularly having excessive daytime sleepiness increased from 9.8% to 12.7% (P trend increases were present in most demographic groups. The largest relative increase was among participants aged 25-34 years (+49%). Increases were also found among participants with hypertension, chronic obstructive pulmonary disease, asthma, and joint pain. Given the deleterious effects of insomnia on health and performance, the increasing prevalence of insomnia and excessive daytime sleepiness among US adults is a potentially troubling development. Published by Elsevier B.V.

  1. Serum drug level-related sodium valproate-induced hair loss.

    Science.gov (United States)

    Ramakrishnappa, Suresh K; Belhekar, Mahesh N

    2013-01-01

    Sodium valproate is a well-established treatment in epilepsy and mood disorders. Its utility is compromised by its adverse effects such as tremor, weight gain, hair loss, and liver dysfunction. Hair loss may occur when drug is used in higher dose. Drug-induced hair loss is diffused and non-scarring, which is reversible upon withdrawal. But there are no case reports showing relation between serum levels of valproate and occurrence of hair loss. So we took interest in reporting this case report.

  2. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  3. Drug induced neutropenia manifesting as oral ulcerations

    Directory of Open Access Journals (Sweden)

    Rachna Kaul

    2009-01-01

    Full Text Available As dental practitioners, we often come across oral ulcerations of varied etiology. Among all the causes of oral ulcers, those due to neutropenia are significant. Neutropenia can occur in many systemic conditions and also in patients on long-term therapy of certain drugs like phenytoin. The diagnosis of neutropenia in time leads to early recognition of the cause of this fatal condition. Here, we report a case of a 50-year-old female patient who developed oral ulcerations secondary to phenytoin-induced neutropenia. Early diagnosis of the condition led to discontinuation of the offending drug and significant improvement in her blood picture and also prevented her from falling prey to many other systemic infections that neutropenia can cause.

  4. Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

    Science.gov (United States)

    Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

    2017-09-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Drug-induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Daba, Mohammad H.; Al-Arifi, Mohammad N; Gubar, Othman A.; El-Tahir, Kamal E.

    2004-01-01

    Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta Tbgf-beta, PDGF, If-I, Et-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspne a, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example Il-I beta and TNF-alpha via activation of nuclear transcription factor Nf-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages and lymphocytes phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system. (author)

  6. Amount of Sleep, Daytime Sleepiness, Hazardous Driving, and Quality of Life of Second Year Medical Students.

    Science.gov (United States)

    Johnson, Kay M; Simon, Nancy; Wicks, Mark; Barr, Karen; O'Connor, Kim; Schaad, Doug

    2017-10-01

    The authors describe the sleep habits of second year medical students and look for associations between reported sleep duration and depression, burnout, overall quality of life, self-reported academic success, and falling asleep while driving. The authors conducted a cross-sectional descriptive study of two consecutive cohorts of second year medical students at a large public university in the USA. Participants completed an anonymous survey about their sleep habits, daytime sleepiness (Epworth sleepiness scale), burnout (Maslach burnout inventory), depression (PRIME MD), and perceived stress (perceived stress scale). Categorical and continuous variables were compared using chi square tests and t tests, respectively. Sixty-eight percent of the students responded. Many (34.3%) reported fewer than 7 h of sleep on typical weeknights, including 6.5% who typically sleep less than 6 h. Twenty-five students (8.4%) reported nodding off while driving during the current academic year. Low typical weeknight sleep (fewer than 6 h vs 6-6.9 h vs 7 or more hours) was associated with (1) higher Epworth sleepiness scale scores, (2) nodding off while driving, (3) symptoms of burnout or depression, (4) decreased satisfaction with quality of life, and (5) lower perceived academic success (all p values ≤0.01). Students reporting under 6 h of sleep were four times more likely to nod off while driving than those reporting 7 h or more. Educational, behavioral, and curricular interventions should be explored to help pre-clinical medical students obtain at least 7 h of sleep most on weeknights.

  7. Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children.

    Science.gov (United States)

    Tran, Yen-Hao; Groen, Henk; Bergman, Jorieke E H; Hak, Eelko; Wilffert, Bob

    2017-03-01

    Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children. We designed a cohort study using a pharmacy prescription database. Pregnant women were considered exposed when they received a prescription of RI-inducing drugs. These drugs could be either used alone (RI+/FAA-) or combined with drugs exhibiting folic acid antagonism (FAA, RI+/FAA+). The reference group included pregnant women who did not receive any RI-inducing drugs or FAA drugs. We analyzed 4116 exposed and 30 422 reference pregnancies. The hazard ratio (HR) with 95% confidence interval (CI) was 1.27 (95%CI 1.15-1.41) for pregnancies exposed to RI-inducing drugs as a whole. Considering subgroups of RI-inducing drugs, prenatal exposure to both RI+/FAA+ and RI+/FAA- was associated with the children's initiation of psychotropic medications, HRs being 1.35 (95%CI 1.10-1.66) and 1.26 (1.13-1.41), respectively. The HRs were increased with prolonged exposure to RI-inducing drugs, especially in the first and second trimesters. In a detailed examination of the psychotropics, the incidences of receiving antimigraine preparations and psychostimulants were significantly increased for the exposed children, compared with the reference children. The incidences of receiving antipsychotics and hypnotics were also higher for the exposed children; however, the HRs did not reach significance after adjustment. We found a significantly increased incident use of psychotropic medications among children prenatally exposed to RI-inducing drugs, especially during the first and second trimesters. This suggests a detrimental effect during critical periods of brain development. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  9. [Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

    Science.gov (United States)

    Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

    2012-01-01

    Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

  10. The effect of chronotype on sleepiness, fatigue, and psychomotor vigilance of ICU nurses during the night shift.

    Science.gov (United States)

    Reinke, Laurens; Özbay, Yusuf; Dieperink, Willem; Tulleken, Jaap E

    2015-04-01

    In general, sleeping and activity patterns vary between individuals. This attribute, known as chronotype, may affect night shift performance. In the intensive care unit (ICR), night shift performance may impact patient safety. We have investigated the effect of chronotype and social demographics on sleepiness, fatigue, and night shift on the performance of nurses. This was a prospective observational cohort study which assessed the performance of 96 ICU night shift nurses during the day and night shifts in a mixed medical-surgical ICU in the Netherlands. We determined chronotype and assessed sleeping behaviour for each nurse prior to starting shift work and before free days. The level of sleepiness and fatigue of nurses during the day and night shifts was determined, as was the effect of these conditions on psychomotor vigilance and mathematical problem-solving. The majority of ICU nurses had a preference for early activity (morning chronotype). Compared to their counterparts (i.e. evening chronotypes), they were more likely to nap before commencing night shifts and more likely to have young children living at home. Despite increased sleepiness and fatigue during night shifts, no effect on psychomotor vigilance was observed during night shifts. Problem-solving accuracy remained high during night shifts, at the cost of productivity. Most of the ICU night shift nurses assessed here appeared to have adapted well to night shift work, despite the high percentage of morning chronotypes, possibly due to their 8-h shift duration. Parental responsibilities may, however, influence shift work tolerance.

  11. Morningness/eveningness chronotype, poor sleep quality, and daytime sleepiness in relation to common mental disorders among Peruvian college students.

    Science.gov (United States)

    Rose, Deborah; Gelaye, Bizu; Sanchez, Sixto; Castañeda, Benjamín; Sanchez, Elena; Yanez, N David; Williams, Michelle A

    2015-01-01

    The study was designed to investigate the association between sleep disturbances and common mental disorders (CMDs) among Peruvian college students. A total of 2538 undergraduate students completed a self-administered questionnaire to gather information about sleep characteristics, sociodemographic, and lifestyle data. Evening chronotype, sleep quality, and daytime sleepiness were assessed using the Horne and Ostberg morningness-eveningness questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, respectivelty. Presence of CMDs was evaluated using the General Health Questionnaire. Logistic regression procedures were used to examine the associations of sleep disturbances with CMDs while accounting for possible confounding factors. Overall, 32.9% of the participants had prevalent CMDs (39.3% among females and 24.4% among males). In multivariable-adjusted logistic models, those with evening chronotype (odds ratios (OR) = 1.43; 95% CI 1.00-2.05), poor sleep quality (OR = 4.50; 95% CI 3.69-5.49), and excessive daytime sleepiness (OR = 1.68; 95% CI 1.41-2.01) were at a relative increased odds of CMDs compared with those without sleep disturbances. In conclusion, we found strong associations between sleep disturbances and CMDs among Peruvian college students. Early education and preventative interventions designed to improve sleep habits may effectively alter the possibility of developing CMDs among young adults.

  12. Construction and validation of the EEG analogues of the Karolinska sleepiness scale based on the Karolinska drowsiness test.

    Science.gov (United States)

    Putilov, Arcady A; Donskaya, Olga G

    2013-07-01

    Simple methods of sleepiness assessment are greatly needed for both fundamental research and practical applications. The Karolinska drowsiness test (KDT) was applied to construct physiological alertness scales and to validate them against such well-known instrument of subjective sleepiness assessment as the Karolinska sleepiness scale (KSS). Seven-min EEG recordings were obtained with 2-h interval from frontal and occipital derivations during the last 32-50 h of 44-61-h wakefulness of 15 healthy study participants. Occipital alpha-theta power difference and frontal and occipital scores on the 2nd principal component of the EEG spectrum were calculated for each one-min interval of 5-min eyes closed section of the record. To obtain scores (from 0 to 5) on alertness scales for each of these EEG indexes, all positive one-min values of the index were assigned to 1, and all remaining (negative) values were assigned to 0. Scores on any of the physiological alertness scales were found to be strongly associated with KSS scores. Physiological analogues of KSS were offered by utilising the EEG recordings on eyes closed interval of KDT. The constructed physiological scales can help in improving validity and user-friendliness of the field and laboratory methods of quantification of drowsy state. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1978-08-25

    A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.

  14. Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNF alpha-Mediated Hepatotoxicity

    NARCIS (Netherlands)

    Fredriksson, Lisa; Wink, Steven; Herpers, Bram; Benedetti, Giulia; Hadi, Mackenzie; de Bont, Hans; Groothuis, Geny; Luijten, Mirjam; Danen, Erik; de Graauw, Marjo; Meerman, John; van de Water, Bob

    Drug-induced liver injury (DILI) is an important clinical problem. Here, we used a genomics approach to in detail investigate the hypothesis that critical drug-induced toxicity pathways act in synergy with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) to cause cell death of

  15. The application of hematopoietic growth factors in drug-induced agranulocytosis: a review of 70 cases

    NARCIS (Netherlands)

    Sprikkelman, A.; de Wolf, J. T.; Vellenga, E.

    1994-01-01

    Since 1989, granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF, G-CSF) have been increasingly applied in the treatment of drug-induced agranulocytosis. In order to evaluate the effectiveness of GM-CSF and G-CSF in the treatment of drug-induced agranulocytosis, we have studied

  16. Synesthetic hallucinations induced by psychedelic drugs in a congenitally blind man.

    Science.gov (United States)

    Dell'Erba, Sara; Brown, David J; Proulx, Michael J

    2018-04-01

    This case report offers rare insights into crossmodal responses to psychedelic drug use in a congenitally blind (CB) individual as a form of synthetic synesthesia. BP's personal experience provides us with a unique report on the psychological and sensory alterations induced by hallucinogenic drugs, including an account of the absence of visual hallucinations, and a compelling look at the relationship between LSD induced synesthesia and crossmodal correspondences. The hallucinatory experiences reported by BP are of particular interest in light of the observation that rates of psychosis within the CB population are extremely low. The phenomenology of the induced hallucinations suggests that experiences acquired through other means, might not give rise to "visual" experiences in the phenomenological sense, but instead gives rise to novel experiences in the other functioning senses. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Sleep patterns and sleepiness among young students: A longitudinal study before and after admission as trainees and apprentices.

    Science.gov (United States)

    Fischer, Frida Marina; Wey, Daniela; Valente, Daniel; Luz, Andréa Aparecida da; Pinheiro, Fernando; Fonseca, Barbara Cristina; Silva-Costa, Aline; Moreno, Claudia Roberta; Menna-Barreto, Luiz; Teixeira, Liliane Reis

    2015-05-01

    In developing countries, youngsters start to work during the high school years. Several studies have shown the difficulties associated with double shift, i.e. to work and study concomitantly, and its negative health consequences. Work and study time, as social synchronizers, have significant effects on the sleep-wake cycle (SWC). The purpose of this study was to evaluate sleep patterns and sleepiness in young students before and after entering the workforce as apprentices or trainees. Participants were 40 adolescents (26 males), 15-18 years old (mean = 15.8 years old) engaged in a first-job program at a non-governmental organization (NGO) while attending evening high school in the outskirts of the city of São Paulo, Brazil. The participants wore actigraphs (Ambulatory Monitoring, Inc.) and registered subjective sleepiness on KSS (Karolinska Sleepiness Scale) along 7 consecutive days, before and after admission to the job. Descriptive analyses were performed, and the variables were tested by means of the t-test and repeated measures ANOVA taking factors day of the week and time of the day into consideration. The participants' sleep duration on weekdays exhibited significant difference before and after starting work (F = 4.55; p = 0.04); the mean sleep duration was 492 min (SD = 44 min) before admission to the job to decrease to 405 min (SD = 58 min) after starting work. The mid-sleep time exhibited significant difference on weekdays before and after starting work (04:57 h; SD = 45 min versus 03:30 h; SD = 54 min; F = 4.91; p = 0.03). Finally, also sleepiness on weekdays (F = 6.41; p = 0.04) and at the waking time (F = 10.75; p sleep restriction. Brazilian governmental incentives notwithstanding, simultaneous performance of several activities by young workers should be considered as an occupational health hazard. Employment policies targeting young workers should take the dual shift - study and work

  18. The Psychosocial Problems of Children with Narcolepsy and Those with Excessive Daytime Sleepiness of Uncertain Origin

    Science.gov (United States)

    Stores, Gregory; Montgomery, Paul; Wiggs, Luci

    2007-01-01

    Background: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong…

  19. Preparation of Tween 80-Zn/Al-Levodopa-Layered Double Hydroxides Nanocomposite for Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Aminu Umar Kura

    2014-01-01

    Full Text Available We incorporated anti-Parkinsonian drug, levodopa (dopa, in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay.

  20. Children's Sleep, Sleepiness, and Performance on Cognitive Tasks.

    Science.gov (United States)

    Buckhalt, Joseph A

    2011-01-01

    While causal connections between sleep deprivation and attention, learning, and memory have been well established in adults, much less research has been done with children. Relations between the amount and quality of sleep and daytime sleepiness have been found for a number of cognitive and academic tasks in several groups of children. These relations have been found for children who have sleep disorders, for children with disorders involving cognitive impairment, and for typically developing children with no known disorders. The research is reviewed here with a focus on the types of cognitive and academic tasks that have been related to insufficient sleep. A series of studies is described that relates sleep parameters to the Woodcock-Johnson® III Tests of Cognitive Abilities and other, similar measures. Implications for educators and psychologists who work with children are discussed.

  1. [Nutritional status, healthy habits, quality of life and daytime sleepiness in nightlife workers of Córdoba].

    Science.gov (United States)

    Moreno Linares, Vicente; Diéguez Cantueso, Inmaculada; Lara Carmona, Juan José; Molina Recio, Guillermo

    2015-04-01

    This study is aimed to analyze the factors that affect body composition, nutritional status, dietary habits, substance abuse (alcohol and smoking), physical activity, sleepiness disorders and self-rated health status in people working in nightlife in the city of Cordoba. Representative sample of 144 subjects (88 men and 56 women) with a mean age of 26.88 (± 4.7) years was studied. Individuals were analized for their body composition. Besides, a personal interview was used to administrate validated questionnaires to get other important data related to the aim of the study. The male group showed higher body mass index (phabits such as drinking alcohol and smoking and at the same time they suffer from sleepiness daytime disorders. In spite of they seems to have a high self-awareness about their own health status, 1 from every 5 individuals recognize that they could improve it. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. DRUG REACTION WITH HERBAL SUPPLEMENT: A POSSIBLE CASE OF DRUG INDUCED LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    AZIZ NA

    2010-01-01

    Full Text Available A 24-year-old lady presented with four days history of fever, non-pruritic rash, ankle pain and swelling. She had consumed herbal supplement five days before the onset of symptoms. Examinations revealed erythematous maculo-papular lesions of varying sizes on sun exposed areas. Patient was suspected to have Drug Induced Lupus Erythematosus (DILE and subsequently symptoms subsided rapidly on withholding the herbal medication.

  3. Dissociating Effects of Global SWS Disruption and Healthy Aging on Waking Performance and Daytime Sleepiness

    Science.gov (United States)

    Groeger, John A.; Stanley, Neil; Deacon, Stephen; Dijk, Derk-Jan

    2014-01-01

    Study Objective: To contrast the effects of slow wave sleep (SWS) disruption and age on daytime functioning. Design: Daytime functioning was contrasted in three age cohorts, across two parallel 4-night randomized groups (baseline, two nights of SWS disruption or control, recovery sleep). Setting: Sleep research laboratory. Participants: 44 healthy young (20-30 y), 35 middle-aged (40-55 y), and 31 older (66-83 y) men and women. Interventions: Acoustic stimulation contingent on appearance of slow waves. Measurements and Results: Cognitive performance was assessed before sleep latency tests at five daily time-points. SWS disruption resulted in less positive affect, slower or impaired information processing and sustained attention, less precise motor control, and erroneous implementation, rather than inhibition, of well-practiced actions. These performance impairments had far smaller effect sizes than the increase in daytime sleepiness and differed from baseline to the same extent for each age group. At baseline, younger participants performed better than older participants across many cognitive domains, with largest effects on executive function, response time, sustained attention, and motor control. At baseline, the young were sleepier than other age groups. Conclusions: SWS has been considered a potential mediator of age-related decline in performance, although the effects of SWS disruption on daytime functioning have not been quantified across different cognitive domains nor directly compared to age-related changes in performance. The data imply that two nights of SWS disruption primarily leads to an increase in sleepiness with minor effects on other aspects of daytime functioning, which are different from the substantial effects of age. Citation: Groeger JA, Stanley N, Deacon S, Dijk DJ. Dissociating effects of global sws disruption and healthy aging on waking performance and daytime sleepiness. SLEEP 2014;37(6):1127-1142. PMID:24882908

  4. Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: A Randomized Clinical Trial.

    Science.gov (United States)

    Videnovic, Aleksandar; Klerman, Elizabeth B; Wang, Wei; Marconi, Angelica; Kuhta, Teresa; Zee, Phyllis C

    2017-04-01

    Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population. To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD. This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016. The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson's Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log-derived and actigraphy-derived metrics. Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson's Disease

  5. [Behavioral impairments in Parkinson's disease].

    Science.gov (United States)

    Kashihara, Kenichi

    2004-09-01

    Behavioral impairments in parkinsonian patients include agitation, hypersexuality, stereotypic movement, pathological gambling, abuse of antiparkinsonian drugs, REM sleep behavioral disorder, and restless legs syndrome. Dementia, psychoses, and emotional disorders, such as depression and anxiety/panic disorder, also impair behavior. Symptoms may be produced by dysfunction of the central nervous system, medication, and/or the psychosocial problems associated with Parkinson's disease. Treatment therefore should be based on the cause of the symptoms seen. In some cases, the reduction or change of antiparkinsonian drugs, or both, may be effective. Treatment of the motor symptoms of Parkinson's disease, including motor fluctuations, may reduce the risk of panic attacks being evoked in the 'off' period. Use of antidepressants, sedatives, and neuroleptics may often be effective. Physicians should identify the causes of the symptoms of behavioral impairment and select appropriate treatments.

  6. Weak relationships between suppression of melatonin and suppression of sleepiness/fatigue in response to light exposure

    NARCIS (Netherlands)

    Ruger, M; Gordijn, MCM; Beersma, DGM; De Vries, B; Daan, S

    In this paper we examine the relationship between melatonin suppression and reduction of sleepiness through light by comparing three different data sets. In total 36 subjects participated in three studies and received 4 h of bright light either from midnight till 4:00 hours (experiments A and B) or

  7. Glucose Modulation Induces Lysosome Formation and Increases Lysosomotropic Drug Sequestration via the P-Glycoprotein Drug Transporter.

    Science.gov (United States)

    Seebacher, Nicole A; Lane, Darius J R; Jansson, Patric J; Richardson, Des R

    2016-02-19

    Pgp is functional on the plasma membrane and lysosomal membrane. Lysosomal-Pgp can pump substrates into the organelle, thereby trapping certain chemotherapeutics (e.g. doxorubicin; DOX). This mechanism serves as a "safe house" to protect cells against cytotoxic drugs. Interestingly, in contrast to DOX, lysosomal sequestration of the novel anti-tumor agent and P-glycoprotein (Pgp) substrate, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), induces lysosomal membrane permeabilization. This mechanism of lysosomal-Pgp utilization enhances cytotoxicity to multidrug-resistant cells. Consequently, Dp44mT has greater anti-tumor activity in drug-resistant relative to non-Pgp-expressing tumors. Interestingly, stressors in the tumor microenvironment trigger endocytosis for cell signaling to assist cell survival. Hence, this investigation examined how glucose variation-induced stress regulated early endosome and lysosome formation via endocytosis of the plasma membrane. Furthermore, the impact of glucose variation-induced stress on resistance to DOX was compared with Dp44mT and its structurally related analogue, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). These studies showed that glucose variation-induced stress-stimulated formation of early endosomes and lysosomes. In fact, through the process of fluid-phase endocytosis, Pgp was redistributed from the plasma membrane to the lysosomal membrane via early endosome formation. This lysosomal-Pgp actively transported the Pgp substrate, DOX, into the lysosome where it became trapped as a result of protonation at pH 5. Due to increased lysosomal DOX trapping, Pgp-expressing cells became more resistant to DOX. In contrast, cytotoxicity of Dp44mT and DpC was potentiated due to more lysosomes containing functional Pgp under glucose-induced stress. These thiosemicarbazones increased lysosomal membrane permeabilization and cell death. This mechanism has critical implications for drug-targeting in

  8. Driver sleepiness, fatigue, careless behavior and risk of motor vehicle crash and injury: Population based case and control study

    Directory of Open Access Journals (Sweden)

    Abdulbari Bener

    2017-10-01

    Conclusion: The current study confirmed that drivers with chronic fatigue, acute sleepiness, and careless driver behavior may significantly increases the risk of road crash which can be lead to serious injury.

  9. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  10. Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

    Science.gov (United States)

    Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

    2015-02-01

    De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

  11. Subjective Sleepiness and Sleep Quality in Adolescents are Related to Objective and Subjective Measures of School Performance.

    NARCIS (Netherlands)

    Boschloo, A.; Krabbendam, L.; Dekker, S.; Lee, N.; Groot, R. de; Jolles, J.

    2013-01-01

    This study investigated the relation between sleep and school performance in a large sample of 561 adolescents aged 11-18 years. Three subjective measures of sleep were used: sleepiness, sleep quality, and sleep duration. They were compared to three measures of school performance: objective school

  12. Calotropis procera Latex-Induced Inflammatory Hyperalgesia—Effect of Antiinflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Raman Sehgal

    2005-01-01

    Full Text Available The milky white latex of plant Calotropis procera produces inflammation of the skin and mucous membranes on accidental exposure. It produces edema on local administration due to the release of histamine and prostaglandins and is associated with hyperalgesia. In the present study we have evaluated the antiedematous and analgesic activity of antiinflammatory drugs against inflammatory response induced by dried latex (DL of C procera in rat paw edema model. An aqueous extract of DL of C procera was injected into the subplantar surface of the rat paw and the paw volume was measured by a plethysmometer at 0, 1, 2, 6, 12, and 24 hours. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test, compression test, and observing the grooming behavior. The inhibitory effect of diclofenac and rofecoxib on edema formation and hyperalgesic response was compared with cyproheptadine (CPH. DL-induced edema formation was maximum at 2 hours that was associated with decreased pain threshold, functional impairment, and grooming. Treatment with antiinflammatory drugs and CPH significantly attenuated the edematous response and grooming, increased the pain threshold, and improved functional parameters. Both antiinflammatory and antiserotonergic drugs significantly inhibited the hyperalgesia associated with DL-induced paw edema. Rofecoxib was found to be superior than diclofenac and was as effective as CPH in ameliorating the hyperalgesia. However, it was found to be less effective than CPH in attenuating edema formation.

  13. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults

    OpenAIRE

    Hwangbo, Young; Kim, Won-Joo; Chu, Min Kyung; Yun, Chang-Ho; Yang, Kwang Ik

    2016-01-01

    Background and Purpose Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. Methods The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous...

  14. Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wei L

    2014-02-01

    Full Text Available Li Wei,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, 2Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Neuroleptic malignant-like syndrome (NMLS is a rare but catastrophic complication of drug treatment for Parkinson's disease (PD. Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson's disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C. At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson's patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. Keywords: antiparkinsonian drugs, creatine kinase, parkinsonism–hyperpyrexia syndrome, respiratory failure

  15. Elevated thyroid stimulating hormone in a neonate: Drug induced or disease?

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2011-01-01

    Full Text Available Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Maternal intake of antithyroid drug can also lead to elevated thyroid stimulating hormone (TSH in a neonate, albeit the scenario is temporary. We report one such interesting case where a clinically euthyroid neonate borne to a mother on antithyroid drug presents on 12 th day of life with reports of elevated TSH and increased tracer uptake in 99mTc thyroid scan. Disproportionately high TSH in comparison to low maternal antithyroid drug dosage and further elevation of TSH after stopping mother′s antithyroid drugs ruled out maternal antithyroid drug-induced congenital hypothyroidism in the baby. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.

  16. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Henninger, Christian; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Schad, Arno; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard

    2012-01-01

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  17. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, Christian [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany); Huelsenbeck, Johannes; Huelsenbeck, Stefanie [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Grösch, Sabine [Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt/Main (Germany); Schad, Arno [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Lackner, Karl J. [Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Kaina, Bernd [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany)

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  18. Rotating shift work, sleep, and accidents related to sleepiness in hospital nurses

    Science.gov (United States)

    Gold, D. R.; Rogacz, S.; Bock, N.; Tosteson, T. D.; Baum, T. M.; Speizer, F. E.; Czeisler, C. A.

    1992-01-01

    A hospital-based survey on shift work, sleep, and accidents was carried out among 635 Massachusetts nurses. In comparison to nurses who worked only day/evening shifts, rotators had more sleep/wake cycle disruption and nodded off more at work. Rotators had twice the odds of nodding off while driving to or from work and twice the odds of a reported accident or error related to sleepiness. Application of circadian principles to the design of hospital work schedules may result in improved health and safety for nurses and patients.

  19. Subjective sleepiness and sleep quality in adolescents are related to objective and subjective measures of school performance

    NARCIS (Netherlands)

    Boschloo, Annemarie; Krabbendam, Lydia; Dekker, Sanne; Lee, Nikki; De Groot, Renate; Jolles, Jelle

    2016-01-01

    This study investigated the relation between sleep and school performance in a large sample of 561 adolescents aged 11–18 years. Three subjective measures of sleep were used: sleepiness, sleep quality, and sleep duration. They were compared to three measures of school performance: objective school

  20. Subjective sleepiness and sleep quality in adolescents are related to objective and subjective measures of school performance

    NARCIS (Netherlands)

    Boschloo, Annemarie; Krabbendam, Lydia; Dekker, Sanne; Lee, Nikki; De Groot, Renate; Jolles, Jelle

    2018-01-01

    This study investigated the relation between sleep and school performance in a large sam- ple of 561 adolescents aged 11–18 years. Three subjective measures of sleep were used: sleepiness, sleep quality, and sleep duration. They were compared to three measures of school performance: objective school

  1. Associations of Drug Lipophilicity and Extent of Metabolism with Drug-Induced Liver Injury.

    Science.gov (United States)

    McEuen, Kristin; Borlak, Jürgen; Tong, Weida; Chen, Minjun

    2017-06-22

    Drug-induced liver injury (DILI), although rare, is a frequent cause of adverse drug reactions resulting in warnings and withdrawals of numerous medications. Despite the research community's best efforts, current testing strategies aimed at identifying hepatotoxic drugs prior to human trials are not sufficiently powered to predict the complex mechanisms leading to DILI. In our previous studies, we demonstrated lipophilicity and dose to be associated with increased DILI risk and, and in our latest work, we factored reactive metabolites into the algorithm to predict DILI. Given the inconsistency in determining the potential for drugs to cause DILI, the present study comprehensively assesses the relationship between DILI risk and lipophilicity and the extent of metabolism using a large published dataset of 1036 Food and Drug Administration (FDA)-approved drugs by considering five independent DILI annotations. We found that lipophilicity and the extent of metabolism alone were associated with increased risk for DILI. Moreover, when analyzed in combination with high daily dose (≥100 mg), lipophilicity was statistically significantly associated with the risk of DILI across all datasets ( p < 0.05). Similarly, the combination of extensive hepatic metabolism (≥50%) and high daily dose (≥100 mg) was also strongly associated with an increased risk of DILI among all datasets analyzed ( p < 0.05). Our results suggest that both lipophilicity and the extent of hepatic metabolism can be considered important risk factors for DILI in humans, and that this relationship to DILI risk is much stronger when considered in combination with dose. The proposed paradigm allows the convergence of different published annotations to a more uniform assessment.

  2. Drug-Induced Myocardial Infarction Secondary to Coronary Artery Spasm in Teenagers and Young Adults

    Directory of Open Access Journals (Sweden)

    Menyar Ayman

    2006-01-01

    Full Text Available There is no published registry for drug-induced acute myocardial infarction (AMI with subsequent patent coronary angiogram in teenagers. To highlight the mechanism and impact of drug-induced MI with patent coronary arteries among teenagers who have relatively few coronary risk factors in comparison with older patients, we conducted a review of the literature. In this review most of the pertinent published (English and non-English articles through the Medline, Scopus, Cochrane Database of Systematic Reviews, and EBSCO Host research databases from 1970 to 2005 have been revised. Teenagers and young adults with AMI and subsequent patent coronary angiogram were included. In those cases drug-induced coronary spasm was highlighted. Among 220 articles (>12000 cases related with AMI with normal coronary angiogram, 50 articles (~100 cases reported the role of drug in AMI secondary to coronary artery spasm (CAS. There is no well-conducted trial for AMI secondary to CAS in young adults but only a series of case reports, and the diagnosis in most of cases was based on the clinical and laboratory findings without provocation. CAS was associated with 12 illicit substances in teenagers (i.e., cocaine, marijuana, alcohol, butane, and amphetamine. Smoking is not only the initiative but also might harbor other illicit substances that increase the risk for CAS. Cocaine-associated AMI is the most frequent in various research papers. CAS was reported with 19 types of medications (i.e., over-the-counter, chemotherapy, antimigraine, and antibiotics without strong relation to age. Despite drug-induced AMI being not a common event, attention to smoking and drugs in teenagers and young adults will have major therapeutic and prognostic implications.

  3. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

    Directory of Open Access Journals (Sweden)

    Sun Woo Sophie Kang

    Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

  4. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

    Science.gov (United States)

    Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

    2016-01-01

    Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

  5. A systematic review of the effect of various interventions on reducing fatigue and sleepiness while driving

    Directory of Open Access Journals (Sweden)

    Seyed Saeed Hashemi Nazari

    2017-10-01

    Full Text Available Purpose: To identify and appraise the published studies assessing interventions accounting for reducing fatigue and sleepiness while driving. Methods: This systematic review searched the following electronic databases: Medline, Science direct, Scopus, EMBASE, PsycINFO, Transport Database, Cochrane, BIOSIS, ISI Web of Knowledge, specialist road injuries journals and the Australian Transport and Road Index database. Additional searches included websites of relevant organizations, reference lists of included studies, and issues of major injury journals published within the past 15 years. Studies were included if they investigated interventions/exposures accounting for reducing fatigue and sleepiness as the outcome, measured any potential interventions for mitigation of sleepiness and were written in English. Meta-analysis was not attempted because of the heterogeneity of the included studies. Results: Of 63 studies identified, 18 met the inclusion criteria. Based on results of our review, many interventions in the world have been used to reduce drowsiness while driving such as behavioral (talking to passengers, face washing, listening to the radio, no alcohol use, limiting the driving behavior at the time of 12 p.m. – 6 a.m. etc, educational interventions and also changes in the environment (such as rumble strips, chevrons, variable message signs, etc. Meta-analysis on the effect of all these interventions was impossible due to the high heterogeneity in methodology, effect size and interventions reported in the assessed studies. Conclusion: Results of present review showed various interventions in different parts of the world have been used to decrease drowsy driving. Although these interventions can be used in countries with high incidence of road traffic accidents, precise effect of each intervention is still unknown. Further studies are required for comparison of the efficiency of each intervention and localization of each intervention

  6. Narcolepsy induced by chronic heavy alcohol consumption: a case report

    Science.gov (United States)

    Wang, Xinyuan

    2012-01-01

    Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone. PMID:25328357

  7. Binding Mode and Induced Fit Predictions for Prospective Computational Drug Design.

    Science.gov (United States)

    Grebner, Christoph; Iegre, Jessica; Ulander, Johan; Edman, Karl; Hogner, Anders; Tyrchan, Christian

    2016-04-25

    Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles.

  8. Effects of school start time on students' sleep duration, daytime sleepiness, and attendance: a meta-analysis.

    Science.gov (United States)

    Bowers, Jennifer M; Moyer, Anne

    2017-12-01

    Research conducted over the past three decades finds that many children and adolescents do not meet recommended sleep guidelines. Lack of sleep is a predictor of a number of consequences, including issues at school such as sleepiness and tardiness. Considering the severity of this public health issue, it is essential to understand more about the factors that may compromise children's and adolescents' sleep. This meta-analysis examined the effects of school start time (SST) on sleep duration of students by aggregating the results of five longitudinal studies and 15 cross-sectional comparison group studies. Results indicated that later starting school times are associated with longer sleep durations. Additionally, later start times were associated with less daytime sleepiness (7 studies) and tardiness to school (3 studies). However, methodological considerations, such as a need for more longitudinal primary research, lead to a cautious interpretation. Overall, this systematic analysis of SST studies suggests that delaying SST is associated with benefits for students' sleep and, thus, their general well-being. Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  9. Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"

    DEFF Research Database (Denmark)

    Linderup, Mette Werner

    Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"......Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"...

  10. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Kostadinova, Radina; Boess, Franziska; Applegate, Dawn; Suter, Laura; Weiser, Thomas; Singer, Thomas; Naughton, Brian; Roth, Adrian

    2013-01-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  11. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  12. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

    Science.gov (United States)

    Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

  13. Excessive Daytime Sleepiness Predicts Neurodegeneration in Idiopathic REM Sleep Behavior Disorder.

    Science.gov (United States)

    Zhou, Junying; Zhang, Jihui; Lam, Siu Ping; Chan, Joey Wy; Mok, Vincent; Chan, Anne; Li, Shirley Xin; Liu, Yaping; Tang, Xiangdong; Yung, Wing Ho; Wing, Yun Kwok

    2017-05-01

    To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD). A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥14 were defined as having EDS. Demographic, clinical, and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model. After a mean follow-up of 5.8 years (SD = 4.3 years), 50 (27.9%) patients developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared to those without EDS (42.2 % vs. 23.1%, p = .01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37 to 4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movements during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinson's disease (PD) (adjusted HR = 3.55, 95% CI 1.59 to 7.89) but not dementia (adjusted HR = 1.48, 95% CI 0.44 to 4.97). EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  14. The impact of daytime sleepiness on the school performance of college students with attention deficit hyperactivity disorder (ADHD): a prospective longitudinal study.

    Science.gov (United States)

    Langberg, Joshua M; Dvorsky, Melissa R; Becker, Stephen P; Molitor, Stephen J

    2014-06-01

    This prospective longitudinal study evaluated the impact of daytime sleepiness on the school performance of 62 college students diagnosed comprehensively with attention deficit hyperactivity disorder. The primary goal of the study was to determine if self-reported daytime sleepiness rated at the beginning of the academic year could predict academic and overall functioning at the end of the academic year while also considering potentially important covariates, including symptoms of inattention, hyperactivity and impulsivity, medication status and whether or not students lived at home or on-campus. Self-reported daytime sleepiness predicted longitudinally school maladjustment, overall functional impairment and the number of D and F grades (i.e. poor and failing) students received in courses above and beyond both self- and parent-report of symptoms, but did not predict overall grade point average. Living at home served as a protective factor and was associated with less school maladjustment and overall impairment. Gender was the only significant predictor in the overall grade point average model, with female gender associated with higher overall grades. The implications of these findings for monitoring and treatment of sleep disturbances in college students with attention deficit hyperactivity disorder are discussed. © 2013 European Sleep Research Society.

  15. The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm.

    Science.gov (United States)

    Qasrawi, Shaden O; Pandi-Perumal, Seithikurippu R; BaHammam, Ahmed S

    2017-09-01

    Studies have shown that experimental fasting can affect cognitive function, sleep, and wakefulness patterns. However, the effects of experimental fasting cannot be generalized to fasting during Ramadan due to its unique characteristics. Therefore, there has been increased interest in studying the effects of fasting during Ramadan on sleep patterns, daytime sleepiness, cognitive function, sleep architecture, and circadian rhythm. In this review, we critically discuss the current research findings in those areas during the month of Ramadan. Available data that controlled for sleep/wake schedule, sleep duration, light exposure, and energy expenditure do not support the notion that Ramadan intermittent fasting increases daytime sleepiness and alters cognitive function. Additionally, recent well-designed studies showed no effect of fasting on circadian rhythms. However, in non-constrained environments that do not control for lifestyle changes, studies have demonstrated sudden and significant delays in bedtime and wake time. Studies that controlled for environmental factors and sleep/wake schedule reported no significant disturbances in sleep architecture. Nevertheless, several studies have consistently reported that the main change in sleep architecture during fasting is a reduction in the proportion of REM sleep.

  16. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

    Science.gov (United States)

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

    2018-02-01

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  17. MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn E

    2017-01-01

    Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential

  18. A high content screening assay to predict human drug-induced liver injury during drug discovery.

    Science.gov (United States)

    Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

    2013-01-01

    Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

  19. Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

    Directory of Open Access Journals (Sweden)

    Gulsah Karaoren

    2016-07-01

    Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

  20. DMH1 (4-[6-(4-isopropoxyphenylpyrazolo[1,5-a]pyrimidin-3-yl]quinoline inhibits chemotherapeutic drug-induced autophagy

    Directory of Open Access Journals (Sweden)

    Yue Sheng

    2015-07-01

    Full Text Available Our previous work found that DMH1 (4-[6-(4-isopropoxyphenylpyrazolo [1,5-a]pyrimidin-3-yl]quinoline was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II (CDDP-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.

  1. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Büsselberg, Dietrich

    2011-01-01

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects

  2. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Energy Technology Data Exchange (ETDEWEB)

    Florea, Ana-Maria [Department of Neuropathology, Heinrich-Heine University, Düsseldorf (Germany); Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha (Qatar)

    2011-03-15

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.

  3. Drug-induced pancreatitis.

    Science.gov (United States)

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.

  4. [Hydroxyurea (hydroxycarbamide)-induced hepatic dysfunction confirmed by drug-induced lymphocyte stimulation test].

    Science.gov (United States)

    Shimizu, Takayuki; Mori, Takehiko; Karigane, Daiki; Kikuchi, Taku; Koda, Yuya; Toyama, Takaaki; Nakajima, Hideaki; Okamoto, Shinichiro

    2014-01-01

    A 62-year-old man with refractory leukemia transformed from myelodysplastic syndrome was placed on hydroxyurea (hydroxycarbamide) at a daily dose of 500 mg. Because of insufficient cytoreductive efficacy, the dose was increased to 1,500 mg five days later. Eight days after the initiation of hydroxyurea, the patient started complaining of chills, fever, and vomiting. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly elevated to 5,098 and 3,880 IU/l from 44 and 59 IU/l in one day, respectively. Tests for hepatitis viruses were all negative. With the discontinuation of hydroxyurea, AST and ALT returned to their former levels within two weeks. A drug-induced lymphocyte stimulation test for hydroxyurea was positive with a stimulating index of 2.0. Hepatic dysfunction has been recognized as one of the side effects of hydroxyurea. However, there have been only a limited number of reports demonstrating drug allergy to have a role in hepatic dysfunction accompanied by fever and gastrointestinal symptoms. The findings of our case strongly suggest that all presentations could be explained by drug allergy. Physicians should be mindful of the potential for acute and severe hepatic dysfunction due to allergic reaction against hydroxyurea.

  5. Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.

    Science.gov (United States)

    Kuroda, Yukihiro; Saito, Madoka

    2010-03-01

    An in vitro method to predict phospholipidosis-inducing potential of cationic amphiphilic drugs (CADs) was developed using biochemical and physicochemical assays. The following parameters were applied to principal component analysis, as well as physicochemical parameters: pK(a) and clogP; dissociation constant of CADs from phospholipid, inhibition of enzymatic phospholipid degradation, and metabolic stability of CADs. In the score plot, phospholipidosis-inducing drugs (amiodarone, propranolol, imipramine, chloroquine) were plotted locally forming the subspace for positive CADs; while non-inducing drugs (chlorpromazine, chloramphenicol, disopyramide, lidocaine) were placed scattering out of the subspace, allowing a clear discrimination between both classes of CADs. CADs that often produce false results by conventional physicochemical or cell-based assay methods were accurately determined by our method. Basic and lipophilic disopyramide could be accurately predicted as a nonphospholipidogenic drug. Moreover, chlorpromazine, which is often falsely predicted as a phospholipidosis-inducing drug by in vitro methods, could be accurately determined. Because this method uses the pharmacokinetic parameters pK(a), clogP, and metabolic stability, which are usually obtained in the early stages of drug development, the method newly requires only the two parameters, binding to phospholipid, and inhibition of lipid degradation enzyme. Therefore, this method provides a cost-effective approach to predict phospholipidosis-inducing potential of a drug. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  6. A systematic review of the sleep, sleepiness, and performance implications of limited wake shift work schedules.

    Science.gov (United States)

    Short, Michelle A; Agostini, Alexandra; Lushington, Kurt; Dorrian, Jillian

    2015-09-01

    The aim of this review was to identify which limited wake shift work schedules (LWSW) best promote sleep, alertness, and performance. LWSW are fixed work/rest cycles where the time-at-work does is ≤8 hours and there is >1 rest period per day, on average, for ≥2 consecutive days. These schedules are commonly used in safety-critical industries such as transport and maritime industries. Literature was sourced using PubMed, Embase, PsycInfo, Scopus, and Google Scholar databases. We identified 20 independent studies (plus a further 2 overlapping studies), including 5 laboratory and 17 field-based studies focused on maritime watch keepers, ship bridge officers, and long-haul train drivers. The measurement of outcome measures was varied, incorporating subjective and objective measures of sleep: sleep diaries (N=5), actigraphy (N=4), and polysomnography, (N=3); sleepiness: Karolinska Sleepiness Scale (N=5), visual analog scale (VAS) alertness (N=2) and author-derived measures (N=2); and performance: Psychomotor Vigilance Test (PVT) (N=5), Reaction Time or Vigilance tasks (N=4), Vector and Letter Cancellation Test (N=1), and subjective performance (N=2). Of the three primary rosters examined (6 hours-on/6 hours-off, 8 hours-on/8 hours-off and 4 hours-on/8 hours-off), the 4 hours-on/8 hours-off roster was associated with better sleep and lower levels of sleepiness. Individuals working 4 hours-on/8 hours-off rosters averaged 1 hour more sleep per night than those working 6 hours-on/6 hours-off and 1.3 hours more sleep than those working 8 hours-on/8 hours-off (Pwork, (ii) more frequent rest breaks, (iii) shifts that start and end at the same clock time every 24 hours, and (iv) work shifts commencing in the daytime (as opposed to night). The findings for performance remain incomplete due to the small number of studies containing a performance measure and the heterogeneity of performance measures within those that did. The literature supports the utility of LWSW in

  7. Comparison of snoring sounds between natural and drug-induced sleep recorded using a smartphone.

    Science.gov (United States)

    Koo, Soo Kweon; Kwon, Soon Bok; Moon, Ji Seung; Lee, Sang Hoon; Lee, Ho Byung; Lee, Sang Jun

    2018-08-01

    Snoring is an important clinical feature of obstructive sleep apnea (OSA), and recent studies suggest that the acoustic quality of snoring sounds is markedly different in drug-induced sleep compared with natural sleep. However, considering differences in sound recording methods and analysis parameters, further studies are required. This study explored whether acoustic analysis of drug-induced sleep is useful as a screening test that reflects the characteristics of natural sleep in snoring patients. The snoring sounds of 30 male subjects (mean age=41.8years) were recorded using a smartphone during natural and induced sleep, with the site of vibration noted during drug-induced sleep endoscopy (DISE); then, we compared the sound intensity (dB), formant frequencies, and spectrograms of snoring sounds. Regarding the intensity of snoring sounds, there were minor differences within the retrolingual level obstruction group, but there was no significant difference between natural and induced sleep at either obstruction site. There was no significant difference in the F 1 and F 2 formant frequencies of snoring sounds between natural sleep and induced sleep at either obstruction site. Compared with natural sleep, induced sleep was slightly more irregular, with a stronger intensity on the spectrogram, but the spectrograms showed the same pattern at both obstruction sites. Although further studies are required, the spectrograms and formant frequencies of the snoring sounds of induced sleep did not differ significantly from those of natural sleep, and may be used as a screening test that reflects the characteristics of natural sleep according to the obstruction site. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury.

    Science.gov (United States)

    Kane-Gill, Sandra L; Smithburger, Pamela L; Kashani, Kianoush; Kellum, John A; Frazee, Erin

    2017-11-01

    Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

  9. Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

    OpenAIRE

    Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

    2016-01-01

    Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

  10. Influence of dietary iodine on drug-induced hypothyrodism in the rat.

    Science.gov (United States)

    Beyssen, M L; Lagorce, J F; Cledat, D; Buxeraud, J

    1999-06-01

    Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased. Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.944+/-0.96 microg/day for chlorpromazine-tested rats, 3.43+/-1.33 microg/day for clomipramine-tested rats, compared with 2.34+/-0.11 microg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland. We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.

  11. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-05-01

    Full Text Available Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

  12. Impact of overnight traffic noise on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers: Results of a pilot study

    Directory of Open Access Journals (Sweden)

    Roland FJ Popp

    2015-01-01

    Full Text Available This study aimed to evaluate the impact of traffic noise along the motorway on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers. This was a randomized, crossover, within-subject controlled study. Healthy long-haul truck drivers spent 6 consecutive nights in a real truck berth with full sleep laboratory equipment. During 3 nights, subjects were exposed to replayed traffic noise alongside motorways, whereas the other 3 nights were without traffic noise. Polysomnography was recorded during the nights and numerous sleepiness tests and vigilance examinations were performed during the following standardized working day. Outcome measures were compared between noisy and silent nights using the paired Wilcoxon test. Ten healthy long-haul truck drivers with a mean age of 36.3 ± 7.3 years completed the study as planned. On noisy nights, subjects had greater latencies to the rapid eye movement (REM phase (90 ± 32 min vs 69 ± 16 min, P = 0.074 and higher percentages of sleep stage 1 (13.7 ± 5.5% vs 11.2 ± 4.4%; P = 0.059. Subjects also rated their sleep quality as having been better during nights without noise (28.1 ± 3.7 vs 30.3 ± 6.2, P = 0.092. The impact of these differences on daytime sleepiness and vigilance was rather low; however, mean Karolinska Sleepiness Scale (KSS scores measured during the course of the following day were higher on six out of eight occasions after noisy nights. The effects of overnight traffic noise on sleep quality are detectable but unlikely to have any major impact on the vigilant attention and driving performance of long haul-truck drivers with low nocturnal noise sensitivity. This might not be true for subgroups prone to sleeping disorders.

  13. Impact of overnight traffic noise on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers: Results of a pilot study.

    Science.gov (United States)

    Popp, Roland Fj; Maier, Stefanie; Rothe, Siegfried; Zulley, Jürgen; Crönlein, Tatjana; Wetter, Thomas C; Rupprecht, Rainer; Hajak, Göran

    2015-01-01

    This study aimed to evaluate the impact of traffic noise along the motorway on sleep quality, sleepiness, and vigilant attention in long-haul truck drivers. This was a randomized, crossover, within-subject controlled study. Healthy long-haul truck drivers spent 6 consecutive nights in a real truck berth with full sleep laboratory equipment. During 3 nights, subjects were exposed to replayed traffic noise alongside motorways, whereas the other 3 nights were without traffic noise. Polysomnography was recorded during the nights and numerous sleepiness tests and vigilance examinations were performed during the following standardized working day. Outcome measures were compared between noisy and silent nights using the paired Wilcoxon test. Ten healthy long-haul truck drivers with a mean age of 36.3 ± 7.3 years completed the study as planned. On noisy nights, subjects had greater latencies to the rapid eye movement (REM) phase (90 ± 32 min vs 69 ± 16 min, P = 0.074) and higher percentages of sleep stage 1 (13.7 ± 5.5% vs 11.2 ± 4.4%; P = 0.059). Subjects also rated their sleep quality as having been better during nights without noise (28.1 ± 3.7 vs 30.3 ± 6.2, P = 0.092). The impact of these differences on daytime sleepiness and vigilance was rather low; however, mean Karolinska Sleepiness Scale (KSS) scores measured during the course of the following day were higher on six out of eight occasions after noisy nights. The effects of overnight traffic noise on sleep quality are detectable but unlikely to have any major impact on the vigilant attention and driving performance of long haul-truck drivers with low nocturnal noise sensitivity. This might not be true for subgroups prone to sleeping disorders.

  14. Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Edoardo Alessandro Pulixi

    Full Text Available BACKGROUND: A high prevalence of obstructive sleep apnea syndrome (OSAS has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD, but few studies have evaluated OSAS in non-morbidly obese NAFLD patients. AIMS: To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage. METHODS: We considered 159 consecutive patients with histological NAFLD and body mass index (BMI 1; 9/13, 69% vs. 39/146, 27%; p = 0.003. At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7-51, p = 0.005 and OR 14.0, 95% c.i. 3.5-70, p = 0.0002, respectively. CONCLUSIONS: A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

  15. Carp edema virus/Koi sleepy disease: an emerging disease in Central-East Europe.

    Science.gov (United States)

    Lewisch, E; Gorgoglione, B; Way, K; El-Matbouli, M

    2015-02-01

    Koi sleepy disease (KSD), also known as carp edema virus (CEV), was first reported from juvenile colour carp in Japan in the 1970s. Recently, this pox virus was detected in several European countries, including Germany, France and the Netherlands. In England, in addition to colour carp, outbreaks in common carp are reported. KSD/CEV is an emerging infectious disease characterized by a typical sleepy behaviour, enophthalmia, generalized oedematous condition and gill necrosis, leading to hypoxia. High mortality, of up to 80-100%, is seen in juvenile koi collected from infected ponds. In Austria, this disease had not been detected until now. In spring 2014, diagnostic work revealed the disease in two unrelated cases. In one instance, a pond with adult koi was affected; in the other, the disease was diagnosed in adult common carp recently imported from the Czech Republic. A survey was carried out on recent cases (2013/2014), chosen from those with similar anamnestic and physical examination findings, revealing a total of 5/22 cases positive for KSD/CEV. In this study, two paradigmatic cases are presented in detail. Results together with molecular evidence shaped the pattern of the first diagnosis of KSD/CEV in fish from Austrian ponds. In the light of the positive cases detected from archived material, and the spread of the disease through live stock, imported from a neighbouring country, the need for epidemiological investigations in Austria and surrounding countries is emphasized. © 2014 Blackwell Verlag GmbH.

  16. [Excessive Daytime Sleepiness, Poor Quality Sleep, and Low Academic Performance in Medical Students].

    Science.gov (United States)

    Machado-Duque, Manuel Enrique; Echeverri Chabur, Jorge Enrique; Machado-Alba, Jorge Enrique

    2015-01-01

    Quality of sleep and excessive daytime sleepiness (EDS) affect cognitive ability and performance of medical students. This study attempts to determine the prevalence of EDS, sleep quality, and assess their association with poor academic performance in this population. A descriptive, observational study was conducted on a random sample of 217 medical students from the Universidad Tecnológica de Pereira, who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Epworth sleepiness scale. Sociodemographic, clinic and academic variables were also measured. Multivariate analyses for poor academic performance were performed. The included students had a mean age of 21.7±3.3 years, of whom 59.4% were men. Almost half (49.8%) had EDS criteria, and 79.3% were poor sleepers (PSQI ≥ 5), while 43.3% had poor academic performance during the last semester. The bivariate analysis showed that having used tobacco or alcohol until intoxicated, fairly bad subjective sleep quality, sleep efficiency < 65%, and being a poor sleeper were associated with increased risk of low performance. Sleep efficiency < 65% was statistically associated with poor academic performance (P=.024; OR = 4.23; 95% CI, 1.12-15.42) in the multivariate analysis. A poor sleep quality determined by low efficiency was related to poor academic achievement at the end of semester in medical students. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  17. Sleepiness at the wheel across Europe: a survey of 19 countries.

    Science.gov (United States)

    Gonçalves, Marta; Amici, Roberto; Lucas, Raquel; Åkerstedt, Torbjörn; Cirignotta, Fabio; Horne, Jim; Léger, Damien; McNicholas, Walter T; Partinen, Markku; Téran-Santos, Joaquín; Peigneux, Philippe; Grote, Ludger

    2015-06-01

    The European Sleep Research Society aimed to estimate the prevalence, determinants and consequences of falling asleep at the wheel. In total, 12 434 questionnaires were obtained from 19 countries using an anonymous online questionnaire that collected demographic and sleep-related data, driving behaviour, history of drowsy driving and accidents. Associations were quantified using multivariate logistic regression. The average prevalence of falling asleep at the wheel in the previous 2 years was 17%. Among respondents who fell asleep, the median prevalence of sleep-related accidents was 7.0% (13.2% involved hospital care and 3.6% caused fatalities). The most frequently perceived reasons for falling asleep at the wheel were poor sleep in the previous night (42.5%) and poor sleeping habits in general (34.1%). Falling asleep was more frequent in the Netherlands [odds ratio = 3.55 (95% confidence interval: 1.97; 6.39)] and Austria [2.34 (1.75; 3.13)], followed by Belgium [1.52 (1.28; 1.81)], Portugal [1.34 (1.13, 1.58)], Poland [1.22 (1.06; 1.40)] and France [1.20 (1.05; 1.38)]. Lower odds were found in Croatia [0.36 (0.21; 0.61)], Slovenia [0.62 (0.43; 0.89)] and Italy [0.65 (0.53; 0.79)]. Individual determinants of falling asleep were younger age; male gender [1.79 (1.61; 2.00)]; driving ≥20 000 km year [2.02 (1.74; 2.35)]; higher daytime sleepiness [7.49 (6.26; 8.95)] and high risk of obstructive sleep apnea syndrome [3.48 (2.78; 4.36) in men]. This Pan European survey demonstrates that drowsy driving is a major safety hazard throughout Europe. It emphasizes the importance of joint research and policy efforts to reduce the burden of sleepiness at the wheel for European drivers.

  18. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    Science.gov (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  19. Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients.

    Science.gov (United States)

    Mizokami, Fumihiro; Takahashi, Yoshiko; Hasegawa, Keiko; Hattori, Hideyuki; Nishihara, Keiji; Endo, Hidetoshi; Furuta, Katsunori; Isogai, Zenzo

    2016-04-01

    Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. © 2015 Japanese Dermatological Association.

  20. Association between Screen Viewing Duration and Sleep Duration, Sleep Quality, and Excessive Daytime Sleepiness among Adolescents in Hong Kong

    Directory of Open Access Journals (Sweden)

    Yim Wah Mak

    2014-10-01

    Full Text Available Screen viewing is considered to have adverse impacts on the sleep of adolescents. Although there has been a considerable amount of research on the association between screen viewing and sleep, most studies have focused on specific types of screen viewing devices such as televisions and computers. The present study investigated the duration with which currently prevalent screen viewing devices (including televisions, personal computers, mobile phones, and portable video devices are viewed in relation to sleep duration, sleep quality, and daytime sleepiness among Hong Kong adolescents (N = 762. Television and computer viewing remain prevalent, but were not correlated with sleep variables. Mobile phone viewing was correlated with all sleep variables, while portable video device viewing was shown to be correlated only with daytime sleepiness. The results demonstrated a trend of increase in the prevalence and types of screen viewing and their effects on the sleep patterns of adolescents.

  1. Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats

    Directory of Open Access Journals (Sweden)

    Sonam Miglani

    2016-10-01

    Full Text Available Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg along with antitubercular drugs (Group III reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p<0.01 compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 ​ units/L, p<0.01 and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p<0.001 levels in Group IV (goat milk 40 mL/kg compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001, respectively. Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p<0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p<0.001 compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.

  2. Drug-induced interstitial lung diseases. Often forgotten

    International Nuclear Information System (INIS)

    Poschenrieder, F.; Stroszczynski, C.; Hamer, O.W.

    2014-01-01

    Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [de

  3. Systemic provocation in doxycycline induced fixed drug eruption: a case report

    Directory of Open Access Journals (Sweden)

    Anik Murwaningsih Rosmarini Estri Sih Hananti Niken Indrastuti

    2014-04-01

    Full Text Available Fixed drug eruption (FDE is recurrent lesions that upon repeated uptake of causative drug, always appears at the same skin and mucosal site. Determination of causal relationship in drug allergy is very important. In this case report, cases of doxycycline-induced FDE was reported. The subject of the research was a 29-year-old male, referred by dermatologist, with history of reccurent FDE. Physical examination revealed an oval well demarcated patch hyperpigmentation. Patch test was perfomed on previous involved and uninvolved site. The result of the patch test was irrelevant. Retesting patch test gave similar result. Systemic provocation test or drug provocation test (DPT  with doxcycline were done with suspected drug under ambulatory survelance and gave positive result. In this case, the DPT succeeded to identify doxycycline as the causal agent of FDE. The work-up of a suspected drug hypersensitivity includes a detailed clinical history, physical examination, skin tests, and provocation tests. The DPT is recommended to confirm drug’s hypersensitivity reactions. Systemic provocation test is considered as the gold standard for diagnosing FDE. Keywords:   fixed drug eruption - doxycycline - causal relationship - patch test - systemic provocation test

  4. Circadian phase, dynamics of subjective sleepiness and sensitivity to blue light in young adults complaining of a delayed sleep schedule.

    Science.gov (United States)

    Moderie, Christophe; Van der Maren, Solenne; Dumont, Marie

    2017-06-01

    To assess factors that might contribute to a delayed sleep schedule in young adults with sub-clinical features of delayed sleep phase disorder. Two groups of 14 young adults (eight women) were compared: one group complaining of a delayed sleep schedule and a control group with an earlier bedtime and no complaint. For one week, each subject maintained a target bedtime reflecting their habitual sleep schedule. Subjects were then admitted to the laboratory for the assessment of circadian phase (dim light melatonin onset), subjective sleepiness, and non-visual light sensitivity. All measures were timed relative to each participant's target bedtime. Non-visual light sensitivity was evaluated using subjective sleepiness and salivary melatonin during 1.5-h exposure to blue light, starting one hour after target bedtime. Compared to control subjects, delayed subjects had a later circadian phase and a slower increase of subjective sleepiness in the late evening. There was no group difference in non-visual sensitivity to blue light, but we found a positive correlation between melatonin suppression and circadian phase within the delayed group. Our results suggest that a late circadian phase, a slow build-up of sleep need, and an increased circadian sensitivity to blue light contribute to the complaint of a delayed sleep schedule. These findings provide targets for strategies aiming to decreasing the severity of a sleep delay and the negative consequences on daytime functioning and health. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Drug Release Profile from Calcium-Induced Alginate-Phosphate Composite Gel Beads

    Directory of Open Access Journals (Sweden)

    Yoshifumi Murata

    2009-01-01

    Full Text Available Calcium-induced alginate-phosphate composite gel beads were prepared, and model drug release profiles were investigated in vitro. The formation of calcium phosphate in the alginate gel matrix was observed and did not affect the rheological properties of the hydrogel beads. X-ray diffraction patterns showed that the calcium phosphate does not exist in crystalline form in the matrix. The initial release amount and release rate of a water-soluble drug, diclofenac, from the alginate gel beads could be controlled by modifying the composition of the matrix with calcium phosphate. In contrast, the release profile was not affected by the modification for hydrocortisone, a drug only slightly soluble in water.

  6. Brugada Phenocopy Induced by Recreational Drug Use

    Directory of Open Access Journals (Sweden)

    Adedoyin Akinlonu

    2018-01-01

    Full Text Available Recreational drugs are commonly abused in all age groups. Intoxication with these substances can induce silent but significant electrocardiographic signs which may lead to sudden death. In this case study, we present a 49-year-old male with no medical comorbidities who came to the emergency department requesting opioid detoxification. Toxicology screen was positive for cocaine, heroin, and cannabis. Initial electrocardiogram (EKG showed features of a Brugada pattern in the right precordial leads, which resolved within one day into admission. This presentation is consistent with the recently recognized clinical entity known as Brugada phenocopy.

  7. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  8. Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

    2016-12-01

    Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

  9. Drug-induced acute interstitial nephritis: A clinicopathological study and comparative trial of steroid regimens

    Directory of Open Access Journals (Sweden)

    R Ramachandran

    2015-01-01

    Full Text Available Steroids are used in the management of drug-induced acute interstitial nephritis (AIN. The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m 2 , partial remission (PR (improvement but eGFR <60 ml/min/1.73 m 2 or resistance (no CR/PR. A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 ΁ 1.1 and 5.1 ΁ 1.2, respectively. At 3 months in Group I, eight patients each (50% achieved CR and PR. In Group II, 8 (61% achieved CR and 5 (39% PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56% was higher in CR as compared to (42% those with PR. ( P = 0.14. Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration ( P = 0.01. Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.

  10. Development of ARDS after Excessive Kath Consumption: A Case Report

    Directory of Open Access Journals (Sweden)

    Marlene Wewalka

    2011-01-01

    Full Text Available Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.

  11. Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Patients With Atrial Fibrillation

    Science.gov (United States)

    Albuquerque, Felipe N.; Calvin, Andrew D.; Sert Kuniyoshi, Fatima H.; Konecny, Tomas; Lopez-Jimenez, Francisco; Pressman, Gregg S.; Kara, Thomas; Friedman, Paul; Ammash, Naser; Somers, Virend K.

    2012-01-01

    Background: An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. Methods: We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. Results: Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m2, and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R2 = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. Conclusions: Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment. PMID:21903736

  12. [Correction of bronchial obstructive syndrome and antituberculous drugs-induced eosinophilia in patients with pulmonary tuberculosis by using plasmapheresis].

    Science.gov (United States)

    Shmelev, E I; Stepanian, I E

    1996-01-01

    The paper provides the results of a follow-up of 70 patients with active pulmonary tuberculosis in whom the administration of antituberculous drugs induced eosinophilia and bronchial obstructive syndrome. To eliminate the side effects of antituberculous therapy, a plasmapheresis regimen was performed in 44 patients, the remaining patients were given only bronchodilators and antihistamine drugs. Plasmapheresis as a means for correcting drug-induced eosinophilia and bronchial obstructive syndrome was found to be more effective than drug therapy and, in some cases, enabled antituberculous therapy to be continued, without changing a combination of drugs. It is recommended that plasmapheresis should be used in cases of inadequate efficiency of conventional methods for correcting drug intolerance.

  13. Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Westra, Inge M.; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, M.T.; Groothuis, Geny M. M.

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict

  14. Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

    Science.gov (United States)

    Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

    2016-04-01

    DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

  15. Drug induced lung disease

    International Nuclear Information System (INIS)

    Schaefer-Prokop, Cornelia; Eisenhuber, Edith

    2010-01-01

    There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

  16. Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Westra, Inge; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Maja; Groothuis, Genoveva

    2013-01-01

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Due to the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict and to

  17. Drug-induced Liver Disease in Patients with Diabetes Mellitus

    OpenAIRE

    Iryna, Klyarytskaya; Helen, Maksymova; Elena, Stilidi

    2016-01-01

    The study presented here was accomplished to assess the course of drug-induced liver diseases in patient’s rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with...

  18. Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

    Science.gov (United States)

    Cordes, Henrik; Thiel, Christoph; Baier, Vanessa; Blank, Lars M; Kuepfer, Lars

    2018-01-01

    Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis , which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.

  19. Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

    Science.gov (United States)

    Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

    2010-07-06

    Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

  20. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient

    Directory of Open Access Journals (Sweden)

    Arup K Misra

    2014-01-01

    Full Text Available Acute renal failure is a life threatening condition. Nonsteroidal antiinflammatory drugs (NSAIDs and cephalosporins are widely used postoperative drugs. NSAID-induced acute renal failure has been reported in the past. In this case, drug interaction and decompensated state of the patient precipitate the condition. NSAIDs inhibit prostaglandins synthesis and thus aggravate ischemia to the kidney that is already facing volume crisis due to surgery. Due to renal dysfunction, plasma ceftriaxone level increases due to decrease clearance and it also acts as nephrotoxic by unknown mechanism. On the other hand, ceftriaxone on its interaction with diclofenac for renal tubular clearance also increases the level of diclofenac and thus further aggravate the ischemia. It is a reversible condition with excluding diclofenac from the treatment regimen and giving adequate hydration to the patient. This highlights the importance of hydration and knowledge of drugs interactions in a postsurgical patient.

  1. Drug induced exocytosis of glycogen in Pompe disease.

    Science.gov (United States)

    Turner, Christopher T; Fuller, Maria; Hopwood, John J; Meikle, Peter J; Brooks, Doug A

    2016-10-28

    Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. The focus of the current study was to identify compounds capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here, calcimycin, lysophosphatidylcholine and α-l-iduronidase each significantly increased glycogen exocytosis compared to vehicle-treated controls. The most effective compound, calcimycin, induced exocytosis through a Ca 2+ -dependent mechanism, although was unable to release a pool of vesicular glycogen larger than the calcimycin-induced exocytic pore. There was reduced glycogen release from Pompe compared to unaffected cells, primarily due to increased granule size in Pompe cells. Drug induced exocytosis therefore shows promise as a therapeutic approach for Pompe patients but strategies are required to enhance the release of large molecular weight glycogen granules. Copyright © 2016. Published by Elsevier Inc.

  2. Radiation retinopathy caused by low dose irradiation and antithyroid drug-induced systemic vasculitis

    International Nuclear Information System (INIS)

    Sonoda, Koh-hei; Ishibashi, Tatsuro

    2005-01-01

    We report on a patient with Graves' disease with radiation retinopathy caused by low-dose irradiation and antithyroid drug-induced antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. A 38-year-old woman with Graves' disease presented with bilateral blurred vision, micro-aneurysms, telangiectasia, and macular edema. The patient was examined by ophthalmoscopy and fluorescein angiography, and radiation retinopathy was diagnosed. The patient had been treated with low-dose irradiation for her Graves' ophthalmopathy a few years earlier. She also had ANCA-positive vasculitis induced by the antithyroid drug (propylthiouracil, PTU) that had been prescribed for her at that time. Because of multiple avascular areas on both retinas, she was treated by intensive retinal photocoagulation to control progressive retinopathy. The radiation doses used to treat Graves' disease ophthalmopathy are low. Nevertheless, there is still a risk of radiation retinopathy developing in patients with PTU-induced ANCA-positive vasculitis. (author)

  3. Drug-Induced Dental Caries: A Disproportionality Analysis Using Data from VigiBase.

    Science.gov (United States)

    de Campaigno, Emilie Patras; Kebir, Inès; Montastruc, Jean-Louis; Rueter, Manuela; Maret, Delphine; Lapeyre-Mestre, Maryse; Sallerin, Brigitte; Despas, Fabien

    2017-12-01

    Dental caries is defined as a pathological breakdown of the tooth. It is an infectious phenomenon involving a multifactorial aetiology. The impact of drugs on cariogenic risk has been poorly investigated. In this study, we identified drugs suspected to induce dental caries as adverse drug reactions (ADRs) and then studied a possible pathogenic mechanism for each drug that had a statistically significant disproportionality. We extracted individual case safety reports of dental caries associated with drugs from VigiBase ® (the World Health Organization global individual case safety report database). We calculated disproportionality for each drug with a reporting odds ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each drug that had a statistically significant disproportionality. In VigiBase ® , 5229 safety reports for dental caries concerning 733 drugs were identified. Among these drugs, 88 had a significant ROR, and for 65 of them (73.9%), no information about dental caries was found in the summaries of the product characteristics, the Micromedex ® DRUGDEX, or the Martindale databases. Regarding the pharmacological classes of drugs involved in dental caries, we identified bisphosphonates, atropinic drugs, antidepressants, corticoids, immunomodulating drugs, antipsychotics, antiepileptics, opioids and β 2 -adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%), bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%) and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the mechanism was unclear. We identified 88 drugs with a significant positive disproportionality for dental caries. Special attention has to be paid to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing hyperglycaemia.

  4. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  5. Reconstruction of Drug-induced Cleft Palate Using Bone Marrow Mesenchymal Stem Cell in Rodents.

    Science.gov (United States)

    Amalraj, Julie Christy; Gangothri, Manasa; Babu, Hari

    2017-01-01

    Triamcinolone acetonide (TAC) (Kenacort*) is a commonly used synthetic glucocorticoid in today's medical practice. The drug is also a potential agent in inducing cleft palates in rats. This drug has been used to induce cleft palate in the fetus of the pregnant rats to bring out a suitable animal model for human cleft lip and palate. The drug was given intraperitoneally to induce congenital cleft palate in pregnant mother rats. The aim of this study is to induce congenital cleft palate in pregnant Wister albino rats and reconstruct the defect with bone marrow mesenchymal stem cells (BMSCs) isolated from the same species along with PLGA (poly lactic co glycolic acid) scaffold. Twenty female animals were divided into two groups. Each group contains 10 animals. The animals were allowed to mate with male rat during the esterase period and the day, in hich vaginal plug was noticed was taken to be day 0. The pregnant rats were given triamcinolone acetonide (Kenacort* 10 mg/1 ml intramuscularly/intravenous [IM/IV] injections) injection intraperitoneally at two different dosages as the existing literature. The injection was given on the 10, 12, and 14 th day of gestation. The clinical changes observed were recorded, and the change in the body weight was noted carefully. Group 1 which received 0.5 mg/kg body weight of TAC had many drug toxic effects. Group 2 which received 0.05 mg/kg body weight produced cleft palate in rat pups. The pups were divided into three groups. Group A control group without cell transplant, the cleft was allowed to close by itself. Group B containing palate reconstructed with plain PLGA scaffold (Bioscaffold, Singapore) without BMSC, Group C containing BMSC and PLGA scaffold (Bioscaffold, Singapore), Group C operated for the cleft palate reconstruction using BMSCs and PLGA scaffold. There was faster and efficient reconstruction of bone in the cleft defect in Group C while there was no defect closure in Group A and B. There was complete

  6. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  7. The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care.

    Science.gov (United States)

    Bosserman, Linda; Prendergast, Franklyn; Herbst, Roy; Fleisher, Martin; Salom, Emery; Strickland, Steven; Raptis, Anastasios; Hallquist, Allan; Perree, Mathieu; Rajurkar, Swapnil; Karimi, Misagh; Rogers, Karl; Davidson, Dirk; Willis, Carl; Penalver, Manuel; Homesley, Howard; Burrell, Matthew; Garrett, Audrey; Rutledge, James; Chernick, Michael; Presant, Cary A

    2012-08-15

    A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development. ©2012 AACR.

  8. Acute nonsteroidal anti-inflammatory drug-induced colitis

    Directory of Open Access Journals (Sweden)

    Massimo Tonolini

    2013-01-01

    Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

  9. Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

    2014-01-01

    BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... therapeutic hypothermia....

  10. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  11. Mouse precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury.

    Science.gov (United States)

    Hadi, Mackenzie; Chen, Yixi; Starokozhko, Viktoriia; Merema, Marjolijn T; Groothuis, Geny M M

    2012-09-17

    Idiosyncratic drug-induced liver injury (IDILI) has been the top reason for withdrawing drugs from the market or for black box warnings. IDILI may arise from the interaction of a drug's reactive metabolite with a mild inflammation that renders the liver more sensitive to injury resulting in increased toxicity (inflammatory stress hypothesis). Aiming to develop a robust ex vivo screening method to study inflammatory stress-related IDILI mechanisms and to find biomarkers that can detect or predict IDILI, mouse precision-cut liver slices (mPCLS) were coincubated for 24 h with IDILI-related drugs and lipopolysaccharide. Lipopolysaccharide exacerbated ketoconazole (15 μM) and clozapine (45 μM) toxicity but not their non-IDILI-related comparators, voriconazole (1500 μM) and olanzapine (45 μM). However, the other IDILI-related drugs tested [diclofenac (200 μM), carbamazepine (400 μM), and troglitazone (30 μM)] did not cause synergistic toxicity with lipopolysaccharide after 24 h of incubation. Lipopolysaccharide further decreased the reduced glutathione levels caused by ketoconazole or clozapine in mPCLS after 24 h of incubation, which was not the case for the other drugs. Lipopolysaccharide significantly increased nitric oxide (NO), cytokine, and chemokine release into the mPCLS media, while the treatment with the drugs alone did not cause any substantial change. All seven drugs drastically reduced lipopolysaccharide-induced NO production. Interestingly, only ketoconazole and clozapine increased the lipopolysaccharide-induced granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) release. Pilot experiments showed that diclofenac and troglitazone, but not carbamazepine, demonstrated synergistic toxicity with lipopolysaccharide after a longer incubation of 48 h in mPCLS. In conclusion, we have developed an ex vivo model to detect inflammatory stress-related liver toxicity and identified ketoconazole, clozapine

  12. Anti-topoisomerase drugs as potent inducers of chromosomal aberrations

    Directory of Open Access Journals (Sweden)

    Loredana Bassi

    2000-12-01

    Full Text Available DNA topoisomerases catalyze topological changes in DNA that are essential for normal cell cycle progression and therefore they are a preferential target for the development of anticancer drugs. Anti-topoisomerase drugs can be divided into two main classes: "cleavable complex" poisons and catalytic inhibitors. The "cleavable complex" poisons are very effective as anticancer drugs but are also potent inducers of chromosome aberrations so they can cause secondary malignancies. Catalytic inhibitors are cytotoxic but they do not induce chromosome aberrations. Knowledge about the mechanism of action of topoisomerase inhibitors is important to determine the best anti-topoisomerase combinations, with a reduced risk of induction of secondary malignancies.As topoisomerases de DNA catalisam alterações topológicas no DNA que são essenciais para a progressão do ciclo celular normal e, portanto, são um alvo preferencial para o desenvolvimento de drogas anticâncer. Drogas anti-topoisomerases podem ser divididas em duas classes principais: drogas anti-"complexos cliváveis" e inibidores catalíticos. As drogas anti-"complexos cliváveis" são muito eficazes como drogas anticancerígenas, mas são também potentes indutores de aberrações cromossômicas, podendo causar neoplasias malignas secundárias. Inibidores catalíticos são citotóxicos mas não induzem aberrações cromossômicas. Conhecimento a respeito do mecanismo de ação de inibidores de topoisomerases é importante para determinar as melhores combinações anti-topoisomerases, com um reduzido risco de indução de neoplasias malignas secundárias.

  13. In Silico Identification of Proteins Associated with Drug-induced Liver Injury Based on the Prediction of Drug-target Interactions.

    Science.gov (United States)

    Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir

    2017-07-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Drug-Induced Hypothermia as Beneficial Treatment before and after Cerebral Ischemia

    DEFF Research Database (Denmark)

    Johansen, Flemming F; Hasseldam, Henrik; Rasmussen, Rune Skovgaard

    2014-01-01

    Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when...... conditioning before (preconditioning) and after (postconditioning) experimental stroke. Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature...... was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced...

  15. Serotonergic Hyperactivity as a Potential Factor in Developmental, Acquired and Drug-Induced Synesthesia

    Directory of Open Access Journals (Sweden)

    Berit eBrogaard

    2013-10-01

    Full Text Available Though synesthesia research has seen a huge growth in recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any among developmental, acquired and drug-induced synesthesia. We know that many forms of synesthesia involve aberrant structural or functional brain connectivity. Proposed mechanisms include direct projection and disinhibited feedback mechanisms, in which information from two otherwise structurally or functionally separate brain regions mix. We also know that synesthesia sometimes runs in families. However, it is unclear what causes its onset. Studies of psychedelic drugs, such as psilocybin, LSD and mescaline, reveal that exposure to these drugs can induce synesthesia. One neurotransmitter suspected to be central to the perceptual changes is serotonin. Excessive serotonin in the brain may cause many of the characteristics of psychedelic intoxication. Excessive serotonin levels may also play a role in synesthesia acquired after brain injury. In brain injury sudden cell death floods local brain regions with serotonin and glutamate. This neurotransmitter flooding could perhaps result in unusual feature binding. Finally, developmental synesthesia that occurs in individuals with autism may be a result of alterations in the serotonergic system, leading to a blockage of regular gating mechanisms. I conclude on these grounds that one commonality among at least some cases of acquired, developmental and drug-induced synesthesia may be the presence of excessive levels of serotonin, which increases the excitability and connectedness of sensory brain regions.

  16. Serotonergic hyperactivity as a potential factor in developmental, acquired and drug-induced synesthesia.

    Science.gov (United States)

    Brogaard, Berit

    2013-01-01

    Though synesthesia research has seen a huge growth in recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any) among developmental, acquired and drug-induced synesthesia. We know that many forms of synesthesia involve aberrant structural or functional brain connectivity. Proposed mechanisms include direct projection and disinhibited feedback mechanisms, in which information from two otherwise structurally or functionally separate brain regions mix. We also know that synesthesia sometimes runs in families. However, it is unclear what causes its onset. Studies of psychedelic drugs, such as psilocybin, LSD and mescaline, reveal that exposure to these drugs can induce synesthesia. One neurotransmitter suspected to be central to the perceptual changes is serotonin. Excessive serotonin in the brain may cause many of the characteristics of psychedelic intoxication. Excessive serotonin levels may also play a role in synesthesia acquired after brain injury. In brain injury sudden cell death floods local brain regions with serotonin and glutamate. This neurotransmitter flooding could perhaps result in unusual feature binding. Finally, developmental synesthesia that occurs in individuals with autism may be a result of alterations in the serotonergic system, leading to a blockage of regular gating mechanisms. I conclude on these grounds that one commonality among at least some cases of acquired, developmental and drug-induced synesthesia may be the presence of excessive levels of serotonin, which increases the excitability and connectedness of sensory brain regions.

  17. Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report.

    Science.gov (United States)

    Etxagibel, Aitziber; Julià, M Rosa; Brotons, Alvaro; Company, M Margarita; Dolz, Carlos

    2008-01-28

    Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

  18. Multimode drug inducible CRISPR/Cas9 devices for transcriptional activation and genome editing

    Science.gov (United States)

    Lu, Jia; Zhao, Chen; Zhao, Yingze; Zhang, Jingfang; Zhang, Yue; Chen, Li; Han, Qiyuan; Ying, Yue; Peng, Shuai; Ai, Runna; Wang, Yu

    2018-01-01

    Abstract Precise investigation and manipulation of dynamic biological processes often requires molecular modulation in a controlled inducible manner. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) has emerged as a versatile tool for targeted gene editing and transcriptional programming. Here, we designed and vigorously optimized a series of Hybrid drug Inducible CRISPR/Cas9 Technologies (HIT) for transcriptional activation by grafting a mutated human estrogen receptor (ERT2) to multiple CRISPR/Cas9 systems, which renders them 4-hydroxytamoxifen (4-OHT) inducible for the access of genome. Further, extra functionality of simultaneous genome editing was achieved with one device we named HIT2. Optimized terminal devices herein delivered advantageous performances in comparison with several existing designs. They exerted selective, titratable, rapid and reversible response to drug induction. In addition, these designs were successfully adapted to an orthogonal Cas9. HIT systems developed in this study can be applied for controlled modulation of potentially any genomic loci in multiple modes. PMID:29237052

  19. Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

    Science.gov (United States)

    Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

    2008-09-01

    Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

  20. Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

    Science.gov (United States)

    Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

    2017-07-01

    In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  1. Functionalized nanoparticles for AMF-induced gene and drug delivery

    Science.gov (United States)

    Biswas, Souvik

    The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the

  2. Correlation between drug–drug interaction-induced Stevens–Johnson syndrome and related deaths in Taiwan

    Directory of Open Access Journals (Sweden)

    Fu-Jen Cheng

    2016-04-01

    Full Text Available Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1 from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA, independent sample t-tests, and odds ratio (OR. In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively, were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049, carbamazepine and sulfamethoxazole/trimethoprim (TMP (p < 0.0001, carbamazepine and phenytoin (p < 0.0001, sulfamethoxazole/TMP and phenytoin (p = 0.015, sulfadoxine and piroxicam (p = 0.045, phenobarbital and cephalexin (p < 0.0001, ampicillin and erythromycin (p < 0.0001, erythromycin and minocycline (p < 0.0001, and vancomycin and ethambutol (p < 0.0001 administered 1 month before the patients' deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore

  3. Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: A case series

    NARCIS (Netherlands)

    D.M.W. Balak (Deepak); J.N.B. Bavinck (Jan Nico Bouwes); De Vries, A.P.J. (Aiko P. J.); Hartman, J. (Jenny); Martino Neumann, H.A. (Hendrik A.); R. Zietse (Bob); H.B. Thio (Bing)

    2016-01-01

    textabstractBackground: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced

  4. Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

    Directory of Open Access Journals (Sweden)

    Seung Ha Lee

    2017-01-01

    Full Text Available Objective Patients with drug-induced parkinsonism (DIP may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. Methods Forty-one DIP patients were classified into normal and abnormal [18F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. Results Twenty-eight patients had normal (Group I and 13 patients had abnormal (Group II scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040. Three patients of Group I and six of Group II had hyposmia (p = 0.018. After drug withdrawal, Group I showed greater improvement in Unified Parkinson’s Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. Conclusion None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

  5. Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome

    DEFF Research Database (Denmark)

    Hinterseer, Martin; Thomsen, Morten Bækgaard; Beckmann, Britt-Maria

    2008-01-01

    Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT inte...... intervals. Here, we evaluate variability of QT intervals in patients with a history of drug-induced long QT syndrome (dLQTS) and TdP in absence of a mutation in any of the major LQTS genes.......Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT...

  6. Effects of a selective educational system on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan

    Directory of Open Access Journals (Sweden)

    Chen TY

    2015-03-01

    Full Text Available Tien-Yu Chen,1,2 Yu-Ching Chou,3 Nian-Sheng Tzeng,1,2,4 Hsin-An Chang,1,2,4 Shin-Chang Kuo,1,2,5 Pei-Yin Pan,1,2 Yi-Wei Yeh,1,2,5 Chin-Bin Yeh,1,2 Wei-Chung Mao1,2,6 1Department of Psychiatry, Tri-Service General Hospital, 2School of Medicine, National Defense Medical Center, 3School of Public Health, National Defense Medical Center, 4Student Counseling Center, National Defense Medical Center, 5Graduate Institute of Medical Sciences, National Defense Medical Center, 6Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, Republic of China Objective: The aim of the study reported here was to clarify the effects of academic pressure on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan. Methods: This cross-sectional study enrolled 757 senior high school adolescents who were classified into four groups: Grade 1 (n=261, Grade 2 (n=228, Grade 3T (n=199; Grade 3 students who had another college entrance test to take, and Grade 3S (n=69; Grade 3 students who had succeeded in their college application. Fatigue, sleep quality, daytime sleepiness, and depression were assessed using the Chinese version of the Multidimensional Fatigue Symptom Inventory – Short Form, Pittsburgh Sleep Quality Index-Taiwan Form, the Chinese version of the Epworth Sleepiness Scale, and the Chinese version of the Beck Depression Inventory®-II (BDI-II, respectively. Results: Physical, emotional, and mental fatigue scores were all higher in higher-grade groups. The Grade 3T (test students had the worst fatigue severity, and the Grade 3S (success students had the least fatigue severity. More than half of the students (60.9% went to bed after 12 am, and they had on average 6.0 hours of sleep per night. More than 30% of the students in Grade 2 (37.3% and Grades 3T/S (30.2%/30.4% possibly had daily sleepiness problems. The students in Grade 3T had the worst BDI-II score (13.27±9.24, and the Grade 3S

  7. Mouse Precision-Cut Liver Slices as an ex Vivo Model To Study Idiosyncratic Drug-Induced Liver Injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Chen, Yixi; Starokozhko, Viktoriia; Groothuis, Geny M. M.; Merema, M.T.

    Idiosyncratic drug-induced liver injury (IDILI) has been the top reason for withdrawing drugs from the market or for black box warnings. IDILI may arise from the interaction of a drug's reactive metabolite with a mild inflammation that renders the liver more sensitive to injury resulting in

  8. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany.

    Science.gov (United States)

    Sarganas, Giselle; Garbe, Edeltraut; Klimpel, Andreas; Hering, Rolf C; Bronder, Elisabeth; Haverkamp, Wilhelm

    2014-01-01

    Drug-induced long QT syndrome (diLQTS) leading to Torsade de Pointes (TdP) is a potentially lethal condition, which has led to several post-marketing drug withdrawals in the past decade. The true incidence of diLQTS/TdP is largely unknown. One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies. To gain more insight into the incidence of diLQTS and TdP, the Berlin Pharmacovigilance Center (PVZ-FAKOS) has actively and prospectively identified patients who developed this particular type of drug-induced adverse event. Here, the basic characteristics of the affected patients are summarized and suspected drugs are discussed. Furthermore, an extrapolation of the Berlin incidence rates to the German Standard Population is presented. Using a Berlin-wide network of 51 collaborating hospitals (>180 clinical departments), adult patients presenting with long QT syndrome (LQTS/TdP) between 2008 and 2011 were identified by active surveillance of these hospitals. Drug exposures as well as other possible risk factors were obtained from the patient's files and in a face-to-face interview with the patient. One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process. The majority (66%) of these cases were female and 60% had developed LQTS/TdP in the outpatient setting. Thirty-five (60%) of 58 confirmed cases were assessed as drug-related based on a standardized causality assessment applying the criteria of the World Health Organization. Drugs assessed as related in more than two cases were metoclopramide, amiodarone, melperone, citalopram, and levomethadone. The age-standardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females. While European annual reporting rates based on spontaneous reports suggest an

  9. Drug-induced immune hemolytic anemia

    Science.gov (United States)

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  10. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults.

    Science.gov (United States)

    Hwangbo, Young; Kim, Won Joo; Chu, Min Kyung; Yun, Chang Ho; Yang, Kwang Ik

    2016-04-01

    Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous month. The question regarding sleep need was "How much sleep do you need to be at your best during the day?" Unmet sleep need was calculated as sleep need minus habitual sleep duration. Participants with a score of >10 on the Epworth Sleepiness Scale were considered to have EDS. The overall prevalence of EDS was 11.9%. Approximately one-third of the participants (31.9%) reported not getting at least 7 hours of sleep. An unmet sleep need of >0 hours was present in 30.2% of the participants. An adjusted multivariate logistic regression analysis revealed a significant excess risk of EDS in the groups with unmet sleep needs of ≥2 hours [odds ratio (OR), 1.80; 95% confidence interval (CI), 1.27-2.54] and 0.01-2 hours (OR, 1.42; 95% CI, 1.02-1.98). However, habitual sleep duration was not significantly related to EDS. EDS was found to be associated with unmet sleep need but not with habitual sleep duration when both factors were examined together. We suggest that individual unmet sleep need is more important than habitual sleep duration in terms of the relation to EDS.

  11. Impact of Multi-Night Experimentally Induced Short Sleep on Adolescent Performance in a Simulated Classroom.

    Science.gov (United States)

    Beebe, Dean W; Field, Julie; Milller, Megan M; Miller, Lauren E; LeBlond, Elizabeth

    2017-02-01

    Investigate whether a realistic "dose" of shortened sleep, relative to a well-rested state, causes a decline in adolescents' learning and an increase in inattentive and sleepy behaviors in a simulated classroom setting. Eighty-seven healthy 14.0- to 16.9-year olds underwent a 3-week sleep manipulation protocol, including two 5-night sleep manipulation conditions presented in a randomly counterbalanced within-subjects cross-over design. Wake time was held constant. Bedtimes were set to induce Short Sleep (SS; 6.5 hours in bed) versus Healthy Sleep (HS; 10 hours in bed). During the morning at the end of each condition, participants underwent a simulated classroom procedure in which they viewed lecture-based educational videotapes and completed relevant quizzes. Their behaviors in the simulated classroom were later coded by condition-blind raters for evidence of inattention and sleepiness. Adolescents had a longer average sleep period during HS (9.1 hours) than SS (6.5 hours). Compared to scores during HS, adolescents scored significantly lower on the quiz, showed more behaviors suggestive of inattention and sleepiness in the simulated classroom, and were reported by adolescents themselves and by their parents to be more inattentive and sleepy during SS. However, the impact of the manipulation on quiz scores was not mediated by changes in attention or sleepiness. Although effect sizes were modest, these findings suggest that previously-reported correlations between sleep duration and academic performance reflect true cause-effect relationships. Findings add to the growing evidence that the chronically shortened sleep experienced by many adolescents on school nights adversely impacts their functioning and health. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  12. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  13. Drug-induced urinary incontinence

    NARCIS (Netherlands)

    Tsakiris, Peter; Oelke, Matthias; Michel, Martin C.

    2008-01-01

    Physiological urinary continence depends on many factors that are potentially vulnerable to adverse drug effects, which may lead to incontinence. In principle, drugs could cause incontinence by lowering bladder outlet resistance and/or by increasing intravesical pressure, which disrupts the normal

  14. Morphologic categorization of cell death induced by mild hyperthermia and comparison with death induced by ionizing radiation and cytotoxic drugs

    International Nuclear Information System (INIS)

    Allan, D.J.; Harmon, B.V.

    1986-01-01

    This paper presents a summary of the morphological categorization of cell death, results of two in vivo studies on the cell death induced by mild hyperthermia in rat small intestine and mouse mastocytoma, and a comparison of the cell death induced by hyperthermia, radiation and cytotoxic drugs. Two distinct forms of cell death, apoptosis and necrosis, can be recognized on morphologic grounds. Apoptosis appears to be a process of active cellular self-destruction to which a biologically meaningful role can usually be attributed, whereas necrosis is a passive degenerative phenomenon that results from irreversible cellular injury. Light and transmission electron microscopic studies showed that lower body hyperthermia (43 degrees C for 30 min) induced only apoptosis of intestinal epithelial cells, and of lymphocytes, plasma cells, and eosinophils. In the mastocytoma, hyperthermia (43 degrees C for 15 min) produced widespread tumor necrosis and also enhanced apoptosis of tumor cells. Ionizing radiation and cytotoxic drugs are also known to induce apoptosis in a variety of tissues. It is attractive to speculate that DNA damage by each agent is the common event which triggers the same process of active cellular self-destruction that characteristically effects selective cell deletion in normal tissue homeostasis

  15. Assessment of time interval between tramadol intake and seizure and second drug-induced attack

    Directory of Open Access Journals (Sweden)

    Bahareh Abbasi

    2015-11-01

    Full Text Available Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years were enrolled in this study. Convulsion was seen in 104 patients (69.3%. In 8 out of 104 patients (7.6% two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3% were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.

  16. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M.

    2010-01-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings

  17. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M., E-mail: vm@szfki.hu [Hungarian Academy of Sciences, Research Institute for Solid State Physics and Optics, Department of Laser Applications, Konkoly Thege Miklós ut 29-33, 1121 Budapest, P.O. Box 49, 1525 Budapest (Hungary)

    2010-07-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings.

  18. Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer.

    Science.gov (United States)

    Jarzabek, Monika A; Proctor, William R; Vogt, Jennifer; Desai, Rupal; Dicker, Patrick; Cain, Gary; Raja, Rajiv; Brodbeck, Jens; Stevens, Dale; van der Stok, Eric P; Martens, John W M; Verhoef, Cornelis; Hegde, Priti S; Byrne, Annette T; Tarrant, Jacqueline M

    2018-01-01

    Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively. Putative mechanistic biomarkers of bevacizumab (bev)-mediated protection against oxaliplatin-induced SD were also investigated. RNA was extracted from whole liver sections or centrilobular regions by laser-capture microdissection (LCM) obtained from NHP administered anti-DLL4 fragment antigen-binding (F(ab')2 or patients with CRLM receiving oxaliplatin-based chemotherapy with or without bev. mRNA expression was quantified using high-throughput real-time quantitative PCR. Significance analysis was used to identify genes with differential expression patterns (false discovery rate (FDR) < 0.05). Eleven (CCL2, CCND1, EFNB2, ERG, ICAM1, IL16, LFNG, NOTCH1, NOTCH4, PRDX1, and TGFB1) and six (CDH5, EFNB2, HES1, IL16, MIK67, HES1 and VWF) candidate genes were differentially expressed in the liver of anti-DLL4- and oxaliplatin-induced SD, respectively. Addition of bev to oxaliplatin-based chemotherapy resulted in differential changes in hepatic CDH5, HEY1, IL16, JAG1, MMP9, NOTCH4 and TIMP1 expression. This work implicates NOTCH and IL16 pathways in the pathogenesis of drug-induced SD and further explains the hepato-protective effect of bev in oxaliplatin-induced SD observed in CRLM patients.

  19. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  20. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  1. The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

    Science.gov (United States)

    Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

    2017-11-01

    In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report

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    Etxagibel Aitziber

    2008-01-01

    Full Text Available Abstract Introduction Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. Case presentation We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Conclusion Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

  3. Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer.

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    Linda Bosserman

    Full Text Available A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes.In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users, or elect to not use the test (non-users.The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73% used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR rate compared to non-users (38.1% vs 0%, p = 0.04 and a higher disease control (CR+PR+Stable rate (81% vs 25%, p<0.01. Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01.The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay.Clinicaltrials.gov NCT00901264.

  4. Diphenhydramine as a Cause of Drug-Induced Liver Injury

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    Yunseok Namn

    2017-01-01

    Full Text Available Drug-induced liver injury (DILI is the most common cause of acute liver failure in the Unites States and accounts for 10% of acute hepatitis cases. We report the only known case of diphenhydramine-induced acute liver injury in the absence of concomitant medications. A 28-year-old man with history of 13/14-chromosomal translocation presented with fevers, vomiting, and jaundice. Aspartate-aminotransferase and alanine-aminotransferase levels peaked above 20,000 IU/L and 5,000 IU/L, respectively. He developed coagulopathy but without altered mental status. Patient reported taking up to 400 mg diphenhydramine nightly, without concomitant acetaminophen, for insomnia. He denied taking other medications, supplements, antibiotics, and herbals. A thorough workup of liver injury ruled out viral hepatitis (including A, B, C, and E, autoimmune, toxic, ischemic, and metabolic etiologies including Wilson’s disease. A liver biopsy was consistent with DILI without evidence of iron or copper deposition. Diphenhydramine was determined to be the likely culprit. This is the first reported case of diphenhydramine-induced liver injury without concomitant use of acetaminophen.

  5. The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model.

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    Qi-Liang Mao-Ying

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.

  6. Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

    Science.gov (United States)

    Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

    2014-01-01

    Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

  7. The impact of meal timing on performance, sleepiness, gastric upset, and hunger during simulated night shift.

    Science.gov (United States)

    Grant, Crystal Leigh; Dorrian, Jillian; Coates, Alison Maree; Pajcin, Maja; Kennaway, David John; Wittert, Gary Allen; Heilbronn, Leonie Kaye; Vedova, Chris Della; Gupta, Charlotte Cecilia; Banks, Siobhan

    2017-10-07

    This study examined the impact of eating during simulated night shift on performance and subjective complaints. Subjects were randomized to eating at night (n=5; 23.2 ± 5.5 y) or not eating at night (n=5; 26.2 ± 6.4 y). All participants were given one sleep opportunity of 8 h (22:00 h-06:00 h) before transitioning to the night shift protocol. During the four days of simulated night shift participants were awake from 16:00 h-10:00 h with a daytime sleep of 6 h (10:00 h-16:00 h). In the simulated night shift protocol, meals were provided at ≈0700 h, 1900 h and 0130 h (eating at night); or ≈0700 h, 0930 h, 1410 h and 1900 h (not eating at night). Subjects completed sleepiness, hunger and gastric complaint scales, a Digit Symbol Substitution Task and a 10-min Psychomotor Vigilance Task. Increased sleepiness and performance impairment was evident in both conditions at 0400 h (phunger and a small but significant elevation in stomach upset across the night (p<0.026). Eating at night was associated with elevated bloating on night one, which decreased across the protocol. Restricting food intake may limit performance impairments at night. Dietary recommendations to improve night-shift performance must also consider worker comfort.

  8. [Drug-induced extrapyramidal disorders].

    Science.gov (United States)

    Horga, J F; Navarro, M; Peiró, V; Hernández, M

    1995-01-01

    We analyze 402 drug-adverse events consisting of movement disorders or aggravation of parkinsonisms, submitted to Sistema Español de Farmacovigilancia until 1994. Our aim is to know patient characteristics and the drugs related with these submissions. Most of them (64) belong to calcium-entry blocker group (31%) and benzamides (27%). Case age intervals more frequent were 11-30 and 60-80 years-old and the events affect predominantly females. The percentage of serious adverse events were near 80%. We think that drug-related parkinsonisms have high prevalence rate and that the role of calcium-entry blockers in these events should be considered at the moment to prescribe groups.

  9. Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis.

    Science.gov (United States)

    Ong, Edmund; Cahill, Catherine

    2015-07-03

    The intracellular trafficking of receptors is a collection of complex and highly controlled processes. Receptor trafficking modulates signaling and overall cell responsiveness to ligands and is, itself, influenced by intra- and extracellular conditions, including ligand-induced signaling. Optimized for use with monolayer-plated cultured cells, but extendable to free-floating tissue slices, this protocol uses immunolabelling and colocalizational analysis to track changes in intracellular receptor trafficking following both chronic/prolonged and acute interventions, including exogenous drug treatment. After drug treatment, cells are double-immunolabelled for the receptor and for markers for the intracellular compartments of interest. Sequential confocal microscopy is then used to capture two-channel photomicrographs of individual cells, which are subjected to computerized colocalizational analysis to yield quantitative colocalization scores. These scores are normalized to permit pooling of independent replicates prior to statistical analysis. Representative photomicrographs may also be processed to generate illustrative figures. Here, we describe a powerful and flexible technique for quantitatively assessing induced receptor trafficking.

  10. Discussion of causes and consequences of sleepiness among college students, 2014

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    Wolgast B

    2016-05-01

    Full Text Available Brad WolgastCenter for Counseling and Student Development, University of Delaware, Newark, DE, USAI was recently directed to, “Causes and consequences of sleepiness among college students”, from Hershner and Chervin.1 As a psychologist who specializes in treating college student sleep problems, I was very pleased to see this article. Overall, it is a gem: thorough, well-conceived, and thoughtful. However, I have concerns about two sections. First, on page 74, Hershner and Chervin1 write, “How much sleep a young adult needs is not clearly known, but is thought to be 8 hours.” They then cite Wehr et al2 as well as Van Dongen et al.3 These choices are surprising as reference for the assertion that young adults need approximately 8 hours of sleep.View original paper by Hershner and Chervin.

  11. The effect of chronotype on sleepiness, fatigue, and psychomotor vigilance of ICU nurses during the night shift

    OpenAIRE

    Reinke, Laurens; Ozbay, Yusuf; Dieperink, Willem; Tulleken, Jaap E.

    2015-01-01

    Purpose In general, sleeping and activity patterns vary between individuals. This attribute, known as chronotype, may affect night shift performance. In the intensive care unit (ICR), night shift performance may impact patient safety. We have investigated the effect of chronotype and social demographics on sleepiness, fatigue, and night shift on the performance of nurses. Methods This was a prospective observational cohort study which assessed the performance of 96 ICU night shift nurses duri...

  12. Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

    Science.gov (United States)

    Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.

    2013-01-01

    Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student’s T-test was used to analyse salivary flows. Critical p-value was established at p0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481

  13. A rare cause of drug-induced hepatitis in an immunocompromised patient and the role of glutathione.

    Science.gov (United States)

    Senadhi, Viplove; Arora, Deepika; Arora, Manish; Marsh, Franklin

    2012-08-27

    The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the most common outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.

  14. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

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    Richard de Boer

    Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

  15. Adenosine A(2A receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

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    Masahiro Mishina

    Full Text Available Adenosine A(2A receptors (A2ARs are thought to interact negatively with the dopamine D(2 receptor (D2R, so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD. However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET with [7-methyl-(11C]-(E-8-(3,4,5-trimethoxystyryl-1,3,7-trimethylxanthine ([(11C]TMSX in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test. In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test. In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an

  16. Drug-related cue induced craving and the correlation between the activation in nucleus accumbens and drug craving: a fMRI study on heroin addicts

    International Nuclear Information System (INIS)

    Wang Yarong; Yang Lanying; Li Qiang; Yang Weichuan; Du Pang; Wang Wei

    2010-01-01

    Objective: To explore the neural mechanism underlying the craving of heroin addicts induced by picture-cue and the correlation between the brain activation degree in nucleus accumbens (NAc)/ the ventral striatum and the scores of patients self-report craving. Methods: Twelve active heroin addicts and 12 matched healthy controls underwent fMRI scan while viewing drug-related pictures and neutral pictures presented in a block design paradigm after anatomical scanning in GE 3.0 T scanner. The fMRI data were analyzed with SPM 5. The change of craving scores was tested by Wilcoxon signed rank test. The Pearson correlation between the activation of NAc/the ventral striatum and the heroin craving score was tested by SPSS 13.0. Results: The craving scores of heroin addicts ranged from 0 to 3.70 (median 0.15) before exposed to drug cue and 0 to 5.10 (median 3.25) after viewing drug-related pictures and showed statistical significance (Z=-2.666, P<0.05). There were 16 activated brain areas when heroin dependent patients exposed to visual drug-related cue vs. neutral visual stimuli. The activation brain regions belonged to two parts, one was limbic system (amygdale, hippocampus, putamen, anterior cingulate cortex and caudate), another was brain cortex (middle frontal cortex, inferior frontal cortex, precentral gyrus, middle temporal cortex, inferior temporal cortex, fusiform gyrus, precuneus and middle occipital gyrus). The MR signal activation magnitude of heroin addicts ranged from 0.19 to 3.50. The result displayed a significant positive correlation between the cue-induced fMRI activation in NAc/the ventral striatum and heroin craving severity (r=0.829, P<0.05). Conclusion: Heroin shared the same neural circuitry in part with other drugs of abuse for cue-induced craving, including brain reward circuitry, visualspatial attention circuit and working memory region. In addition, the dysfunction of NAc/the ventral striatum may attribute to heroin-related cue induced craving

  17. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

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    Christiane Schneider-Gold

    Full Text Available Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2. We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM.12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.Clinical symptoms were depression (more pronounced in DM2, excessive daytime sleepiness (more pronounced in DM1, reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment

  18. [Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

    Science.gov (United States)

    Suemaru, K; Kawasaki, H; Gomita, Y

    1997-06-01

    The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

  19. Neurofeedback Effects on Evoked and Induced EEG Gamma Band Reactivity to Drug-related Cues in Cocaine Addiction

    Science.gov (United States)

    Horrell, Timothy; El-Baz, Ayman; Baruth, Joshua; Tasman, Allan; Sokhadze, Guela; Stewart, Christopher; Sokhadze, Estate

    2010-01-01

    Introduction Preoccupation with drug and drug-related items is a typical characteristic of cocaine addicted individuals. It has been shown in multiple accounts that prolonged drug use has a profound effect on the EEG recordings of drug addicts when compared to controls during cue reactivity tests. Cue reactivity refers to a phenomenon in which individuals with a history of drug abuse exhibit excessive psychophysiological responses to cues associated with their drug of choice. One of the aims of this pilot study was to determine the presence of an attentional bias to preferentially process drug-related cues using evoked and induced gamma reactivity measures in cocaine addicts before and after biobehavioral treatment based on neurofeedback. Another aim was to show that central SMR amplitude increase and frontal theta control is possible in an experimental outpatient drug users group over 12 neurofeedback sessions. Method Ten current cocaine abusers participated in this pilot research study using neurofeedback combined with Motivational Interviewing sessions. Eight of them completed all planned pre- and post –neurofeedback cue reactivity tests with event-related EEG recording and clinical evaluations. Cue reactivity test represented a visual oddball task with images from the International Affective Picture System and drug-related pictures. Evoked and induced gamma responses to target and non-target drug cues were analyzed using wavelet analysis. Results Outpatient subjects with cocaine addiction completed the biobehavioral intervention and successfully increased SMR while keeping theta practically unchanged in 12 sessions of neurofeedback training. The addition of Motivational Interviewing helped retain patients in the study. Clinical evaluations immediately after completion of the treatment showed decreased self-reports on depression and stress scores, and urine tests collaborated reports of decreased use of cocaine and marijuana. Effects of neurofeedback resulted

  20. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    Science.gov (United States)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.