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Sample records for antiparkinsonian drug-induced sleepiness

  1. Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects

    Science.gov (United States)

    Micallef, Joëlle; Rey, Marc; Eusebio, Alexandre; Audebert, Christine; Rouby, Frank; Jouve, Elisabeth; Tardieu, Sophie; Blin, Oliver

    2009-01-01

    AIMS To assess the sleepiness induced by pramipexole, a D2/D3-dopamine receptor agonist commonly used in Parkinson's disease and restless legs syndrome, without the problem of the confounding factors related to the disease. METHODS Placebo, bromocriptine (2.5 mg), L-dopa (100 mg) and pramipexole (0.5 mg) were administered in a single oral dose on four separate days, with at least a 2-week wash-out period in a randomized cross-over design. Induced somnolence was assessed using Multiple Sleep Latency Test (MSLT) and subjective scaling of vigilance. Twelve male subjects (26.3 ± 5.5 years old) without anxiety, mood, sleep or sedation disorders were enrolled. RESULTS Pramipexole significantly reduced mean sleep latency compared with placebo 3 h 30 min [−6.1 min (−9.8, −2.4), P = 0.002] and 5 h 30 min [−5.6 min (−7.7, −3.5), P = 0.003] after administration. In addition, the total duration of sleep during the tests was higher with pramipexole than with placebo [+6.0 min (2.3, 9.7), P < 0.001]. These differences were not observed with L-dopa and bromocriptine in comparison with placebo. The induced sleepiness was not associated with an increase in subjective somnolence scaling, indicating that this adverse event may occur without prior warning. CONCLUSIONS These results show that a single oral dose of pramipexole induces sleepiness as assessed by MSLT in healthy young subjects, independent of disease-related sleep dysfunction. PMID:19220275

  2. Antiparkinsonian medication and pathological gambling.

    Science.gov (United States)

    Lader, Malcolm

    2008-01-01

    Parkinson's disease is a common condition, usually treated by dopaminergic agents, both ergot and non-ergot. Many behavioural abnormalities are associated with such usage, including impulse control disorders (ICDs), dopamine dysregulation syndrome and 'punding'. Pathological gambling, a form of ICD, comprises persistent and maladaptive gambling of various types that disrupts personal, family or occupational activity. Pathological gambling may be associated with other abnormal actions such as pathological shopping, hoarding and hypersexuality. The incidence varies widely from study to study but may be up to 7% of users of dopaminergic agents. Recognition of this problem has led drug regulatory agencies to add precautions concerning pathological gambling to official drug information for the entire class of antiparkinsonian medications. The literature is not entirely consistent and opinions differ greatly, but pramipexole (a dopamine D2 and D3 agonist), and perhaps ropinirole (also a D2/D3 agonist), may be especially likely to be associated with pathological gambling, although the precise nature of the relationship is unclear. Treatment involves reducing the dose of the medication or switching to another medication; unfortunately, the Parkinson's disease may worsen. The mechanism of this adverse effect is believed to be excessive dopaminergic stimulation but probably not specifically involving D3 receptors. A parallel to addictive behaviour with stimulant drugs has been noted.

  3. 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 ...

  4. 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...

  5. [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.

  6. 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 ...

  7. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  8. Drug-induced thrombocytopenic purpura

    OpenAIRE

    Sathiasekar, Anisha Cynthia; Deepthi, D. Angeline; Sathia Sekar, G. Suresh

    2015-01-01

    Drug-induced thrombocytopenic purpura is a skin condition result from a low platelet count due to drug-induced anti-platelet antibodies caused by drugs. Drug-induced thrombocytopenic purpura should be suspected when a patient, child or adult, has sudden, severe thrombocytopenia. Drug-induced thrombocytopenic purpura is even more strongly suspected when a patient has repeated episodes of sudden, severe thrombocytopenia

  9. Excessive Daytime Sleepiness

    Directory of Open Access Journals (Sweden)

    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

  10. Drug-induced liver injuries

    African Journals Online (AJOL)

    2011-06-02

    Jun 2, 2011 ... Drug-induced liver injury (DILI) is a term increasingly being used by most clinicians and is synonymous with drug-induced hepatotoxicity. A succinct definition of a DILI is 'a liver injury induced by a drug or herbal medicine resulting in liver test abnormalities or liver dysfunction with a reasonable exclusion of ...

  11. Drug-induced hypothyroidism

    Directory of Open Access Journals (Sweden)

    Leonardo F. L. Rizzo

    2017-10-01

    Full Text Available The thyroid axis is particularly prone to interactions with a wide variety of drugs, whose list increases year by year. Hypothyroidism is the most frequent consequence of drug-induced thyroid dysfunction. The main mechanisms involved in the development of primary hypothyroidism are: inhibition of the synthesis and/or release of thyroid hormones, immune mechanisms related to the use of interferon and other cytokines, and the induction of thyroiditis associated with the use of tyrosine kinase inhibitors and drugs blocking the receptors for vascular endothelial growth factor. Central hypothyroidism may be induced by inhibition of thyroid-stimulating hormone (bexarotene or corticosteroids or by immunological mechanisms (anti-CTLA4 or anti-PD-1 antibody drugs. It is also important to recognize those drugs that generate hypothyroidism by interaction in its treatment, either by reducing the absorption or by altering the transport and metabolism of levothyroxine. Thus, it is strongly recommended to evaluate thyroid function prior to the prescription of medications such as amiodarone, lithium, or interferon, and the new biological therapies that show important interaction with thyroid and endocrine function in general.

  12. Drug-induced lupus erythematosus

    Science.gov (United States)

    ... kidney inflammation (nephritis) can develop with drug-induced lupus caused by TNF inhibitors or with ANCA vasculitis due to hydralazine or levamisole. Nephritis may require treatment with prednisone and immunosuppressive medicines. Avoid taking the ...

  13. 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 ...

  14. 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...

  15. Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder

    Science.gov (United States)

    Massari, Caio M.; López-Cano, Marc; Núñez, Fabiana; Fernández-Dueñas, Víctor; Tasca, Carla I.; Ciruela, Francisco

    2017-01-01

    Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the neuroprotective effects of GUO have been corroborated in cellular models of Parkinson’s disease (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD animal models. Accordingly, we evaluated the effectiveness of GUO in reversing motor impairments in several rodent movement disorder models, including catalepsy, tremor, and hemiparkinsonism. Our results showed that orally administered GUO antagonized reserpine-mediated catalepsy, reduced reserpine-induced tremulous jaw movements, and potentiated the number of contralateral rotations induced by L-3,4-dihydroxyphenylalanine in unilaterally 6-hydroxidopamine-lesioned rats. In addition, at 5 and 7.5 mg/kg, GUO inhibited L-DOPA-induced dyskinesia in rats chronically treated with a pro-dopaminergic agent. Overall, we describe the therapeutic potential of GUO, which may be effective not only for reversing parkinsonian motor impairments but also for reducing dyskinesia induced by treatment for PD. PMID:29046640

  16. Drug-induced Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Yoshino Minoura

    2013-04-01

    Full Text Available Brugada syndrome (BrS is an inherited cardiac disorder that is associated with an electrocardiogram pattern of ST segment elevation on right precordial leads and a high incidence of sudden death. Diagnosis requires documentation of a coved-type ST segment that occurs spontaneously or in the presence of a class IA or IC antiarrhythmic agent. A wide variety of other drugs, including antianginals, antidepressants, antipsychotics, and antihistamines, have been reported to unmask or induce the electrocardiographic and arrhythmic manifestations of BrS. This review focuses on drug-induced BrS phenotypes, prevalence, and underlying mechanisms.

  17. An analytical review on probable anti-parkinsonian effect of modafinil

    Directory of Open Access Journals (Sweden)

    Mehdi Farhoudi

    2013-12-01

    Full Text Available Restoring dopamine levels in Parkinson's disese (PD has been considered as the main symptomatic therapy. In this strategy, long-term administration of L-DOPA results in motor impairments. This necessitates novel approaches in that PD is tackled with lower deleterious side effects. . Modafinil is a wake promoting agent clinically used for treatment of excessive day time sleeping. This medication increases dopamine levels and decreases oxidative stress and can thus exert anti-parkinsonian effect. Therefore, this review will give an account of the probable anti-parkinsonian mechanisms of modafinil.

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

    Science.gov (United States)

    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.

  19. Drugs induced pulmonary arterial hypertension.

    Science.gov (United States)

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized 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 appetite suppressant 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 arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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. ...

  2. Caffeine: sleep and daytime sleepiness.

    Science.gov (United States)

    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.

  3. Drug-induced hyperthermia in Huntington's disease

    NARCIS (Netherlands)

    Gaasbeek, D; Naarding, Paul; Stor, T; Kremer, H P H

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic

  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 the antioxidant potential of antiparkinsonian drugs in different in vitro models

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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...

  8. 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.

  9. [Drug-induced autoimmune hemolytic anemia].

    Science.gov (United States)

    Homberg, J C

    1999-04-03

    AUTOANTIBODY PRODUCTION: The production of autoantibodies can only occur if immune tolerance is circumvented. Thus drug-induced autoimmune hemolytic anemia requires that the drug have an effect on both autoantigens and on the immune system. AN EXAMPLE, METHYLDOPA: Methyldopa is a hypotensive agent which induces major production of anti-Rh IgG anti-erythrocyte autoantibodies, anti-nuclear antibodies and anti-actin antibodies. These autoantibodies generally appear 6 months after treatment onset and are observed in 20% of treated patients. Hemolysis is however exceptional and is only clinically or biologically perceptible in 1 to 2% of the patients who become immunized. Induced lupus has been reported as have been several dozen cases of drug-induced hepatitis with anti-actin autoantibodies. DRUGS INDUCING HEMOLYTIC ANEMIA: Besides methyldopa, other drugs known to induce hemolytic anemia include levodopa used for Parkinson's disease, mefenamic acid, a nonsteroidal antiinflammatory drug, interferon-alpha, used in chronic viral hepatitis, cyclosporin used for the prevention of graft rejection and the treatment of certain autoimmune diseases, and fludarabin, used in chronic lymphoid leukemia. If there is no clinical or biological expression, the drug can be continued, excepting fludarabin where regular controls are needed. If hemolytic anemia is patent, the drug must be discontinued, transfusion and corticosteroid therapy should be envisaged.

  10. Drug-induced hemolytic anemia: Pharmacological aspects.

    Science.gov (United States)

    Renard, D; Rosselet, A

    2017-09-01

    Drug-induced hemolytic anemia is a very rare but potentially lethal adverse drug reaction, which can take the form of oxidative damage to vulnerable erythrocytes (as in glucose-6-phosphate dehydrogenase deficiency), drug-induced thrombotic microangiopathy, or immune-mediated hemolytic anemia. For each form, distinctive drugs are documented as potential triggers. When a formal diagnosis of hemolytic anemia is made following drug administration, a structured approach is recommended to assess the plausibility of an adverse drug reaction based on chronological sequence, epidemiological data, objective evidence (when available), and ruling out of non-drug causes. For suspicions of immune-mediated hemolytic anemia, investigations by a laboratory with specific expertise are crucial given the complexity of the field. If there is good reason to believe hemolytic anemia is drug-induced, immediate drug discontinuation is necessary and corticosteroid administration can be considered. The clinical pharmacology specialist can support evaluation of drug imputability and report the case to the pharmacovigilance system, an important last step in managing such events. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Drug-induced Brugada syndrome: Clinical characteristics and risk factors

    NARCIS (Netherlands)

    Konigstein, Maayan; Rosso, Raphael; Topaz, Guy; Postema, Pieter G.; Friedensohn, Limor; Heller, Karin; Zeltser, David; Belhassen, Bernard; Adler, Arnon; Viskin, Sami

    2016-01-01

    Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. The

  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. 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.

  14. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    . 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...... further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention....

  15. Drugs Induced Stevens-Johnson Syndrome

    Directory of Open Access Journals (Sweden)

    Elif ÖNDER

    2010-05-01

    Full Text Available Stevens Johnson Syndrome (SJS is a life threatening mucocutaneous skin disease that mostlydeveloped after using some drug. SJS mostly appear between 2-4th decades. Mucocutaneouslesions were seen between 1-14 days of drug intake. And these lesions spread diffusely all aroundthe body. First treatment choice is the stopping of drug that cause SJS and giving supportingtreatment. After understanding of underlying cytotoxic and immunological mechanism of SJS,new treatment approaches were developed and mortality of disease was reduced. We hereinreport a short review of drug induced SJS and its treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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 spon......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...... from the original report, or from another health care provider who reported the event. GPs were contacted and asked to recruit the patient as well as two age, gender and drug matched controls. Patients were asked to fill a questionnaire and provide a buccal swab DNA sample through the mail. DNA samples...

  18. Spectrum of Drug-induced Chronic Diarrhea.

    Science.gov (United States)

    Philip, Nissy A; Ahmed, Nazir; Pitchumoni, Capecomorin S

    2017-02-01

    The evaluation of a patient with chronic diarrhea can be quite frustrating, as it is expensive and involves multiple diagnostic studies. Moreover, identification of a drug as a cause of chronic diarrhea is a challenge in patients taking multiple medications. The disease may either be associated with intestinal mucosal changes, mimicking diseases such as celiac disease, or purely functional, with no histopathologic change. Drug-induced diarrhea may or may not be associated with malabsorption of nutrients, and a clinical improvement may occur within days of discontinuation of the drug, or may take longer when associated with mucosal injury. Diarrhea in diabetics, often attributed to poor management and lack of control, may be due to oral hypoglycaemic agents. Chemotherapy can result in diffuse or segmental colitis, whereas olmesartan and a few other medications infrequently induce a disease that mimics celiac disease, but is not associated with gluten intolerance. In short, increased awareness of a drug, as a cause for diarrhea and a clear understanding of the clinical manifestations will help clinicians to solve this challenging problem. This article aims to review drug-induced diarrhea to (a) understand known pathophysiological mechanisms; (b) assess the risk associated with frequently prescribed medications, and discuss the pathogenesis; and (c) provide easily retrievable data in tables to help identify known offending medication/s and a list of top 100 prescribed medications in the United States as a useful comprehensive reference.

  19. Drug induced acute pancreatitis: Does it exist?

    Science.gov (United States)

    Tenner, Scott

    2014-01-01

    As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones (ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis. PMID:25469020

  20. Drug-induced acid-base disorders.

    Science.gov (United States)

    Kitterer, Daniel; Schwab, Matthias; Alscher, M Dominik; Braun, Niko; Latus, Joerg

    2015-09-01

    The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine).

  1. 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.

  2. Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

    Science.gov (United States)

    van Eimeren, T; Pellecchia, G; Cilia, R; Ballanger, B; Steeves, T D L; Houle, S; Miyasaki, J M; Zurowski, M; Lang, A E; Strafella, A P

    2010-11-09

    Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls). Following overnight withdrawal of antiparkinsonian medication, patients were studied with H₂(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback. We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity. We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.

  3. 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.

  4. Drug-induced cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

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

    2017-01-01

    : 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......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......, 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...

  5. Drug-Induced Oxidative Stress and Toxicity

    Directory of Open Access Journals (Sweden)

    Damian G. Deavall

    2012-01-01

    Full Text Available Reactive oxygen species (ROS are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.

  6. Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity.

    Science.gov (United States)

    Weinreb, Orly; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H

    2010-11-01

    Rasagiline (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO)-B inhibitor, anti-Parkinsonian drug. Rasagiline is effective as monotherapy or adjunct to L-Dopa for patients with early and late Parkinson's disease (PD). Its S-isomer, TVP1022 is thousand times less potent as an MAO-B inhibitor. However, both compounds have similar molecular mechanisms of neuroprotection in neuronal cell cultures and animal neurodegenerative models, indicating that the neuroprotective effect of rasagiline does not depend on inhibition of MAO-B, but rather is associated with the N-propargyl moiety, which promotes mitochondrial viability and stabilizes permeability transition by regulating Bcl-2 family proteins. Novel findings demonstrated that the major metabolite of rasagiline, 1-(R)-aminoindan has antioxidant and neuroprotective capabilities and thus, may contribute to the overt activity of its parent compound, rasagiline. This paper will review the earlier and present studies in the development of rasagiline for treatment of PD and discuss its pharmacology and applicable mechanism of action. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Management of drug-induced hyperbilirubinaemia in early pregnancy

    African Journals Online (AJOL)

    lymphocyte stimulation tests for piperidolate hydrochloride were negative, but in view of the patient's clinical course we concluded that her hyperbilirubinaemia was caused by drug-induced hepatotoxicity. Management of drug-induced hyperbilirubinaemia in early pregnancy. H Tsuyoshi, K Nishijima, J Takahashi, Y Yoshida.

  10. Drug-induced exanthem following dabigatran.

    Science.gov (United States)

    Whitehead, Heather; Boyd, J Michael; Blais, Danielle M; Hummel, John

    2011-10-01

    To report an incident of a drug-induced exanthem during treatment with dabigatran in a patient without prior exposure to the drug. A 20-year-old white male was prescribed oral dabigatran 150 mg twice daily for thromboembolic prevention because of nonvalvular atrial fibrillation. After 2 weeks of dabigatran therapy, a raised, pruritic, erythematous rash developed on the patient's inner thigh and forearm. Upon discontinuation of dabigatran and initiation of oral corticosteroid treatment, the rash resolved. Dabigatran therapy was not readministered and thromboembolic prevention therapy with warfarin was instituted. The clinical evidence for efficacy of dabigatran was derived largely from the RE-LY trial, which provided an open-label comparison with warfarin for the reduction of stroke and systemic embolism in nonvalvular atrial fibrillation. The most frequent adverse reactions leading to discontinuation of dabigatran were bleeding and gastrointestinal events. In the RE-LY study, drug hyper-sensitivity, allergic edema, anaphylactic reaction, and anaphylactic shock were reported in <0.1% of patients receiving dabigatran. Despite the low incidence of hypersensitivity reported in the RE-LY trial, the use of the Naranjo probability scale indicated a probable relationship between the rash and dabigatran therapy in this patient. Upon initiation of dabigatran therapy, surveillance for hyper-sensitivity reactions should be included as part of routine drug monitoring.

  11. Drug-induced psoriasis: clinical perspectives

    Directory of Open Access Journals (Sweden)

    Balak DMW

    2017-12-01

    . Keywords: psoriasis, drug-induced, psoriasiform, cutaneous drug reaction, beta-blocker, lithium, monoclonal antibodies, small molecules

  12. Melatonin modulates drug-induced acute porphyria

    Directory of Open Access Journals (Sweden)

    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

  13. Predicting sleepiness during an awake craniotomy.

    Science.gov (United States)

    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.

  14. Drug-induced Brugada syndrome: Clinical characteristics and risk factors.

    Science.gov (United States)

    Konigstein, Maayan; Rosso, Raphael; Topaz, Guy; Postema, Pieter G; Friedensohn, Limor; Heller, Karin; Zeltser, David; Belhassen, Bernard; Adler, Arnon; Viskin, Sami

    2016-05-01

    Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome. Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed to define characteristics that identify patients prone to developing this complication. For each patient with drug-induced Brugada syndrome who had an ECG recorded in the absence of drugs, we included 5 healthy controls matched by gender and age. All ECGs were evaluated for Brugada-like abnormalities. Seventy-four cases of drug-induced Brugada syndrome from noncardiac medications were identified: 77% were male, and drug toxicity was involved in 46%. Drug-induced Brugada syndrome from oral medications generally occurred weeks after the initiation of therapy. Mortality was 13%. By definition, all cases had a type I Brugada pattern during drug therapy. Nevertheless, their ECG in the absence of drugs was more frequently abnormal than the ECG of controls (56% vs 33%, P = .04). Drug-induced Brugada syndrome from noncardiac drugs occurs predominantly in adult males, is frequently due to drug toxicity, and occurs late after the onset of therapy. Minor changes are frequently noticeable on baseline ECG, but screening is impractical because of a prohibitive false-positive rate. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. Drug Induced Hearing Loss: Researchers Study Strategies to Preserve Hearing

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Drug-Induced Hearing Loss Researchers Study Strategies to Preserve ... brain there was a sound. What are ototoxic drugs and why are they important? Ototoxic drugs are ...

  16. Drug-Induced QT Prolongation And Torsades de Pointes

    OpenAIRE

    Li, Matthew; Ramos, Liz G.

    2017-01-01

    Torsades de pointes (TdP)—an uncommon but life-threatening polymorphic ventricular tachycardia—is almost always drug induced. The authors describe the causes, risk factors, symptoms, diagnosis, and treatment of TdP.

  17. Stavudine, an anti‑retroviral drug induces reactive astrocytes in ...

    African Journals Online (AJOL)

    Stavudine, an anti‑retroviral drug induces reactive astrocytes in motor cortex of albino mice. Agnes A. Nwakanma, Theresa B. Ekanem, Moses B. Ekong, Mokutima A. Eluwa, Eme E. Osim, Terkula Kpela ...

  18. Structure-based design, synthesis and molecular modeling studies of thiazolyl urea derivatives as novel anti-parkinsonian agents.

    Science.gov (United States)

    Azam, Faizul; Prasad, Medapati Vijaya Vara; Thangavel, Neelaveni; Shrivastava, Anil Kumar; Mohan, Govind

    2012-11-01

    Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts to discover novel antiparkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative stress in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of 2-chloro,5-trifluoromethyl substituted analog, halogen substituted derivatives exhibited moderate antiparkinsonian activity. The results of biochemical investigations from brain homogenate of mice outline the importance of neuroprotective/antioxidant therapy for Parkinson's disease (PD), supporting the notion that the oxidative stress may play a significant role in the pathophysiological mechanisms underlying PD. Molecular docking studies of these compounds with adenosine A(2A) receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human A(2A) receptor for the design and development of potent antagonists. Parameters for Lipinski's rule of 5 were calculated computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties of a compound. None of the synthesized compounds violated Lipinski's rule, making them suitable drug candidate for the treatment of PD.

  19. Drug-Path: a database for drug-induced pathways.

    Science.gov (United States)

    Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. © The Author(s) 2015. Published by Oxford University Press.

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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

  4. 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, ...

  5. Proposal of cutoff points for pediatric daytime sleepiness scale to identify excessive daytime sleepiness.

    Science.gov (United States)

    Meyer, Carolina; Barbosa, Diego Grasel; Junior, Geraldo Jose Ferrari; Andrade, Rubian Diego; Silva, Diego Augusto Santos; Pelegrini, Andreia; Gomes Felden, Érico Pereira

    2018-03-01

    The objective of the present study was to propose cutoff points for the Pediatric Daytime Sleepiness Scale (PDSS) through sensitivity and specificity analyses in order to identify excessive daytime sleepiness, considering parameters such as duration and quality of sleep, health perception, stress control and depressive moods (feelings of sadness) in adolescents. A total of 1,132 adolescents, aged 14-19 years old, of both sexes, from the public high school of São José - SC, answered the questionnaire with information on age, daytime sleepiness, sleep duration, health perception, stress management, depressive moods (feelings of sadness) and quality of sleep. The Receiver Operating Characteristic (ROC) curve was used to estimate cutoff points considering the sensitivity and specificity values ​​that best identify adolescents with excessive daytime sleepiness, using independent variables as a reference. The majority of the sample was female (54.2%), aged 14-16 years. The girls presented worse quality of sleep (66.4%), and the boys had a more positive perception of health (74.8%), better stress control (64.8%) and lower depressive moods (feelings of sadness) (63.3%). The largest area in the ROC curve was the one that considered sleep quality as a parameter in both sexes (area of the curve = 0.709 and 0.659, respectively, for boys and girls, p sleep quality as a reference, the cutoff point for excessive daytime sleepiness was 15 points. The other parameters used were also significant (p sleep quality was the parameter most strongly related to daytime sleepiness, and a cutoff of 15 points for the PDSS for both sexes should be used in the definition of excessive daytime sleepiness. For the other parameters, stress management, depressive mood (feelings of sadness) and health perception, different cutoff points are suggested for boys and girls.

  6. Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rat 6-Hydroxydopamine Model; The Role of Malondialdehyde

    Directory of Open Access Journals (Sweden)

    Sarookhani

    2016-08-01

    Full Text Available Background The current study evaluated the effects of a combination of flunarizine (flu a calcium channel blocker, glibenclamide (Glib, a KATP channels blocker and B vitamins (B com on the behavioral symptoms of 6-hydroxydopamine (6-OHDA-induced model of Parkinson disease to examine the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress.

  7. 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.

  8. Drug-Induced Metabolic Acidosis [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Amy Quynh Trang Pham

    2015-12-01

    Full Text Available Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics.

  9. Observation and Interview-based Diurnal Sleepiness Inventory for measurement of sleepiness in older adults

    Directory of Open Access Journals (Sweden)

    Pak VM

    2017-09-01

    Full Text Available Victoria M Pak,1,2 S-Hakki Onen,3,4 Nalaka S Gooneratne,4 Bruno Falissard,5 Fannie Onen4–6 1Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, 2Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA; 3CHU Lyon, Hôpital Edouard Herriot, Geriatric Sleep Medicine Center, Lyon, France; 4Division of Geriatric Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 5CHU Bichat Claude Bernard, Gériatrie, APHP, Paris, 6CESP, INSERM 1018 & 1178, Université Paris Sud, Paris, France Introduction: There is no established reference standard for subjective measures of sleepiness in older adults. Methods: This study compares the Observation and Interview-based Diurnal Sleepiness Inventory (ODSI with two existing instruments for measurement of sleepiness and daily functioning, the Epworth Sleepiness Scale (ESS and Functional Outcomes of Sleep Questionnaire (FOSQ. Results: A total of 125 study participants were included in this study and were administered the ODSI, ESS and FOSQ; subjects had a mean age of 70.9 ± 5.27 years, mean Apnea–Hypopnea Index of 31.9 ± 27.9 events/hour and normal cognitive functioning (Mini-Mental State Examination score > 24. The ODSI showed a significant association with the ESS (Spearman’s ρ: 0.67, P < 0.001 and with the FOSQ (Spearman’s ρ: –0.52, P < 0.001. The ODSI 1 item (assessing sleepiness in active situations was borderline significantly correlated with the ESS (β = 0.14; 95% confidence interval [CI], –0.01 to 0.29; P = 0.069. ODSI 2 item (sleepiness in passive situations was correlated with the ESS (β = 1.65; 95% CI, 1.32 to 1.98; P < 0.001. Both ODSI 1 (β = –0.15; 95% CI, –0.24 to –0.07; P < 0.001 and ODSI 2 (β = –0.35; 95% CI, –0.55 to 0.16; P < 0.001 were significantly correlated with the FOSQ. Conclusion: The ODSI is a suitable measure of sleepiness and is appropriate for

  10. Drug induced aseptic meningitis: A diagnostic challenge | Frank ...

    African Journals Online (AJOL)

    Drug-induced aseptic meningitis (DIAM) is a rare but important and often challenging diagnosis for the physician. Intake of antimicrobials, steroids, analgesics amongst others has been implicated. Signs and symptoms generally develop within 24-48 hours of drug ingestion. The patient often exhibits the classic symptoms of ...

  11. Pattern Of Drug Induced Hyperuricaemia In Nigerians With ...

    African Journals Online (AJOL)

    Thirty-one patients with newly diagnosed pulmonary tuberculosis were longitudinally studied between January 1997 and June 1998; each for 6 months to determine the pattern of drug induced hyperuricaemia. Biochemical indices determined were serum urate and 24 hours urinary output of urate, before and during ...

  12. The prevalence of drug induced hepatotoxicity among HIV positive ...

    African Journals Online (AJOL)

    Introduction: Drug induced hepatotoxicity is a recognized problem associated with the anti-tuberculosis (anti-TB) chemotherapy and is of great concern especially in this era of HIV infection. Objectives: To obtain the prevalence of hepatotoxicity due to anti-TB medications in HIV positive and negative patients with pulmonary ...

  13. 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...

  14. Management of drug-induced hyperbilirubinaemia in early pregnancy

    African Journals Online (AJOL)

    We report on two pregnant women who developed severe drug-induced hepatic failure and hyperbilirubinaemia during the period of fetal organogenesis. ... of the drug suspected to be causing the condition is the optimal management, immediately decreasing the maternal bilirubin level and improving the perinatal ...

  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. 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 ...

  17. 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.

  18. Driver sleepiness on YouTube: A content analysis.

    Science.gov (United States)

    Hawkins, A N; Filtness, A J

    2017-02-01

    Driver sleepiness is a major contributor to severe crashes and fatalities on our roads. Many people continue to drive despite being aware of feeling tired. Prevention relies heavily on education campaigns as it is difficult to police driver sleepiness. The video sharing social media site YouTube is extremely popular, particularly with at risk driver demographics. Content and popularity of uploaded videos can provide insight into the quality of publicly accessible driver sleepiness information. The purpose of this research was to answer two questions; firstly, how prevalent are driver sleepiness videos on YouTube? And secondly, what are the general characteristics of driver sleepiness videos in terms of (a) outlook on driver sleepiness, (b) tone, (c) countermeasures to driver sleepiness, and, (d) driver demographics. Using a keywords search, 442 relevant videos were found from a five year period (2nd December 2009-2nd December 2014). Tone, outlook, and countermeasure use were thematically coded. Driver demographic and video popularity data also were recorded. The majority of videos portrayed driver sleepiness as dangerous. However, videos that had an outlook towards driver sleepiness being amusing were viewed more often and had more mean per video comments and likes. Humorous videos regardless of outlook, were most popular. Most information regarding countermeasures to deal with driver sleepiness was accurate. Worryingly, 39.8% of videos with countermeasure information contained some kind of ineffective countermeasure. The use of humour to convey messages about the dangers of driver sleepiness may be a useful approach in educational interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. 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

  20. Drug-induced leukocytoclastic vasculitis: tigecycline a rare cause

    Directory of Open Access Journals (Sweden)

    Kalpana Bhairavarasu

    2015-01-01

    Full Text Available Drug-induced leukocytoclastic vasculitis is an inflammation of blood vessels triggered by various drugs. It presents with a localized skin rash but may involve the internal organ systems, including the gastrointestinal tract, kidneys, lungs, central nervous system, and joints. The clinical recognition of drug-induced vasculitis is very important because continued use of the culprit drug can be organ or life threatening. The prognosis is excellent if the disease is limited to the skin and diagnosed promptly. The use of tigecycline has recently increased due to resistance patterns of bacteria, and it is important to recognize this potential adverse effect of this drug and to diagnose and treat the patient early to achieve a favorable outcome. To best of our knowledge, we report the first case of tigecycline-induced leukocytoclastic vasculitis.

  1. Sleep and daytime sleepiness in methylphenidate medicated and ...

    African Journals Online (AJOL)

    Objective: Excessive daytime sleepiness due to any cause can result in various symptoms similar to those used for the diagnosis of attention deficit/hyperactivity disorder (ADHD). A common treatment for children diagnosed with ADHD is methylphenidate which is also used to treat excessive daytime sleepiness. This paper ...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Sonolência excessiva Excessive daytime sleepiness

    Directory of Open Access Journals (Sweden)

    Lia Rita Azeredo Bittencourt

    2005-05-01

    Full Text Available A sonolência é uma função biológica, definida como uma probabilidade aumentada para dormir. Já a sonolência excessiva (SE, ou hipersonia, refere-se a uma propensão aumentada ao sono com uma compulsão subjetiva para dormir, tirar cochilos involuntários e ataques de sono, quando o sono é inapropriado. As principais causas de sonolência excessiva são a privação crônica de sono (sono insuficiente, a Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono (SAHOS, a narcolepsia, a Síndrome das Pernas Inquietas/Movimentos Periódicos de Membros (SPI/MPM, Distúrbios do Ritmo Circadiano, uso de drogas e medicações e a hipersonia idiopática. As principais conseqüências são prejuízo no desempenho nos estudos, no trabalho, nas relações familiares e sociais, alterações neuropsicológicas e cognitivas e risco aumentado de acidentes. O tratamento da sonolência excessiva deve estar voltado para as causas específicas. Na privação voluntária do sono, aumentar o tempo de sono e higiene do sono, o uso do CPAP (Continuous Positive Airway Pressure na Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono, exercícios e agentes dopaminérgicos na Síndrome das Pernas Inquietas/Movimentos Periódicos de Membros, fototerapia e melatonina nos Distúrbios do Ritmo Circadiano, retiradas de drogas que causam sonolência excessiva e uso de estimulantes da vigília.Sleepiness is a physiological function, and can be defined as increased propension to fall asleep. However, excessive sleepiness (ES or hypersomnia refer to an abnormal increase in the probability to fall asleep, to take involuntary naps, or to have sleep atacks, when sleep is not desired. The main causes of excessive sleepiness is chronic sleep deprivation, sleep apnea syndrome, narcolepsy, movement disorders during sleep, circadian sleep disorders, use of drugs and medications, or idiopathic hypersomnia. Social, familial, work, and cognitive impairment are among the consequences of

  6. Sleepiness in sleepwalking and sleep terrors: a higher sleep pressure?

    Science.gov (United States)

    Carrillo-Solano, Marisol; Leu-Semenescu, Smaranda; Golmard, Jean-Louis; Groos, Elisabeth; Arnulf, Isabelle

    2016-10-01

    To identify the determinants of excessive daytime sleepiness in adults with sleepwalking or sleep terrors (SW/ST). We collected the charts of all consecutive adult patients admitted from 2012 to 2014 for SW/ST. They had completed the Paris Arousal Disorders Severity Scale and the Epworth Sleepiness Scale, and had undergone one (n = 34) or two consecutive (n = 124) nocturnal videopolysomnographies. The demographic, clinical, and sleep determinants of excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score of greater than 10) were analyzed. Almost half (46.8%) of the 158 adult patients with SW/ST reported excessive daytime sleepiness. They had shorter sleep onset latencies (in night 1 and night 2), shorter REM sleep latencies, longer total sleep time, and higher REM sleep percentages in night 2, but no greater clinical severity of the parasomnia than patients without sleepiness. The level of sleepiness correlated with the same measures (sleep onset latency on both nights, REM sleep onset latency, and total sleep time in night 2), plus the latency to N3. In the regression model, higher sleepiness was determined by shorter sleep onset latency on night 1, lower number of awakenings in N3 on night 1, and higher total sleep time on night 2. Daytime sleepiness in patients with SW/ST is not the consequence of disturbed sleep but is associated with a specific polygraphic phenotype (rapid sleep onset, long sleep time, lower numbers of awakenings on N3) that is suggestive of a higher sleep pressure that may contribute to incomplete arousal from N3. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Daytime sleepiness and related factors in nursing students.

    Science.gov (United States)

    Demir, Gökçe

    2017-12-01

    Evaluation of the frequency and causes of daytime sleepiness in nursing students because it is an important factor in improving the health status of the students, controlling sleep problems, improving students' academic achievements, and maintaining a healthy lifestyle. The aim of this study was to determine the prevalence of daytime sleepiness in nursing students and the factors associated with it. A cross-sectional research design was used in this study. Nursing students (n=382). Data were collected using a questionnaire prepared by the authors to assess socio-demographic characteristics, sleep habits, and problems of nursing students and the Epworth Sleepiness Scale (ESS), which assesses daytime sleepiness. Descriptive statistics included numbers, percentages, mean, median, and standard deviation. Mann-Whitney U test (Z) and Kruskal-Wallis (KW) analysis of variance were used for evaluating the relationship between ESS scores and independent variables. The prevalence of daytime sleepiness in the students was found to be 10.5%. Those in the 2nd grade, who were married, who did not consume coffee or tea, lived alone, regarded their own academic achievement as poor, and used the Internet during morning hours experienced increased daytime sleepiness. Moreover, students who talk in their sleep, grind their teeth, feel restless before sleep, experience problems in falling asleep, and wake up at night were found to experience increased daytime sleepiness. Daytime sleepiness is a considerably common health problem in nursing students. This study found that daytime sleepiness is associated with individual characteristics, lifestyle and consumption habits, and sleep habits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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

  9. Drug-induced angioedema: experience of Italian emergency departments.

    Science.gov (United States)

    Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F

    2014-06-01

    Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

  10. Epidemiology, Mechanisms, and Diagnosis of Drug-Induced Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Maria Isabel Montañez

    2017-05-01

    Full Text Available Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators by mast cells and basophils. Although anaphylaxis is often under-communicated and thus underestimated, its incidence appears to have risen over recent decades. Drugs are among the most common triggers in adults, being analgesics and antibiotics the most common causal agents. Anaphylaxis can be caused by immunologic or non-immunologic mechanisms. Immunologic anaphylaxis can be mediated by IgE-dependent or -independent pathways. The former involves activation of Th2 cells and the cross-linking of two or more specific IgE (sIgE antibodies on the surface of mast cells or basophils. The IgE-independent mechanism can be mediated by IgG, involving the release of platelet-activating factor, and/or complement activation. Non-immunological anaphylaxis can occur through the direct stimulation of mast cell degranulation by some drugs, inducing histamine release and leading to anaphylactic symptoms. Work-up of a suspected drug-induced anaphylaxis should include clinical history; however, this can be unreliable, and skin tests should also be used if available and validated. Drug provocation testing is not recommended due to the risk of inducing a harmful reaction. In vitro testing can help to confirm anaphylaxis by analyzing the release of mediators such as tryptase or histamine by mast cells. When immunologic mechanisms are suspected, serum-sIgE quantification or the use of the basophil activation test can help confirm the culprit drug. In this review, we will discuss multiple aspects of drug-induced anaphylaxis, including epidemiology, mechanisms, and diagnosis.

  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. The mechanobiology of drug-induced cardiac valve disease.

    Science.gov (United States)

    Lam, Ngoc Thien; Balachandran, Kartik

    2015-01-01

    Drug-related adverse reactions leading to valve disease or valvulopathy were first identified in the 1960s. These were associated with patients taking anti-migraine ergot-derivative drugs, anti-anorectics, anti-Parkinson's drugs, or other anti-depressant drugs. In general, these drugs have serotonergic, dopaminergic, or β-adrenergic activity, being either agonists or reuptake inhibitors of the aforementioned neurotransmitter pathways. Recent work has focused on several possible mechanisms for valvulopathy, specifically highlighting the serotonin or 5-hydroxy-trypta-mine-2B (5-HT2B) receptor subtype and the 5-HT transporter as mediators that cause expression of myofibroblast phenotype, excessive cell proliferation, leading to valve fibrosis. Most of these studies and reviews, however, were not reported in the context of the mechanical environment of the valve, which by itself is an important factor in the initiation and progression of valve disease. It is also not known whether patients who have altered mechanical environments in their cardiovascular system, such as those who are hypertensive or have functional cardiac disease, such as ischemic ventricular dilation, or those who have an increased propensity for developing drug-induced valvulopathy. In the present review, we highlight the potential role of hemodynamics and the mechanical environment in influencing these drug-induced valvulopathies, focusing on serotonin-mediated disease and the need for further study of this topic.

  13. Drug-Induced Ocular Hypertension and Angle-Closure Glaucoma.

    Science.gov (United States)

    Badhu, Badri P; Bhattarai, Balkrishna; Sangraula, Himal P

    2013-01-01

    The objective of this study was to review the available literature on the drugs causing ocular hypertension and glaucoma. Electronic literature search was carried out using the Web sites www.pubmed.gov and www.google.com published through the year 2011. The search words were "drug induced ocular hypertension" and "drug induced glaucoma" used in combination. The articles published or translated into English were studied. Quite a significant number of drugs commonly prescribed by various physicians of different specialties can induce ocular hypertension or glaucoma. A brief account of various drugs that can induce ocular hypertension has been given in this article. Those drugs are parasympatholytics; steroids; anticholinergics, adrenergics, and antidepressants; cholinomimetics; antineoplastic agents; antipsychotic and antiparkinsonism agents; H1 and H2 receptor blockers; botulinum toxin, cardiac agents, and anticoagulants; silicone oil; sulfa drugs; and anesthetic agents. Rational use of these drugs and knowledge of their potential adverse effects can help prevent the devastating complications resulting in loss of vision and compromised quality of life.

  14. Objective daytime sleepiness in patients with somnambulism or sleep terrors.

    Science.gov (United States)

    Lopez, Régis; Jaussent, Isabelle; Dauvilliers, Yves

    2014-11-25

    To objectively measure daytime sleepiness and to assess for clinical and polysomnographic determinants of mean sleep latency in adult patients with somnambulism (sleepwalking [SW]) or sleep terrors (ST) compared with controls. Thirty drug-free adult patients with primary SW or ST, and age-, sex-, and body mass index-matched healthy controls underwent a standardized clinical interview, completed questionnaires including the Epworth Sleepiness Scale, and underwent one night of video polysomnography followed by the Multiple Sleep Latency Test (MSLT). Excessive daytime sleepiness defined as Epworth Sleepiness Scale score >10 was reported in 66.7% of patients and 6.7% of controls. The temporal pattern of sleep latencies in individual MSLT trials differed between patients and controls, with progressive increased sleep latency in patients across the trials in contrast to a "U curve" for controls. We did not find between-group differences regarding the mean sleep latency on the 5 MSLT trials, but did observe reduced sleep latencies in patients for the first 2 trials. Despite increased slow-wave sleep disruptions found in patients (i.e, more micro-arousals and hypersynchronous high-voltage delta waves arousals), we did not find polysomnographic characteristic differences when comparing sleepy patients for either subjective or objective daytime sleepiness on the MSLT compared with alert patients. Excessive daytime sleepiness is a common complaint in subjects with SW or ST and shorter sleep latencies in the early morning hours. Despite an increased slow-wave sleep fragmentation found in these patients, we did not identify any association with the level of daytime sleepiness. © 2014 American Academy of Neurology.

  15. Monitoring driver's sleepiness on-board for preventing road accidents.

    Science.gov (United States)

    Papadelis, Christos; Lithari, Chrysa; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Portouli, Evangelia; Bekiaris, Evangelos

    2009-01-01

    Driver sleepiness due to sleep deprivation is a causative factor of many road accidents. Reducing the extent of the sleepy driving problem by developing a countermeasure device that will monitor the sleepiness level of the driver is crucial to improve the safety of the roads. Among numerous physiological measurements, the electroencephalographic (EEG) signal seems to be the most sensitive to detect sleepiness. Previous studies in the field have found consistent alterations of EEG signal during sleepy driving, though they face methodological limitations. We present here preliminary results from a real-driving experiment in which a more complete experimental setup was followed. The subjects were exposed to driving conditions twice: once after they had a normal sleep during the previous night, and once after they remained awake for at least 24 hours prior to the experiment. Significant alterations were observed in the alpha and beta EEG frequencies bands between the two sessions. Electroopthalmographic (EOG) measurements revealed an increased number of eye blinking during the sleep-deprived session in comparison to the control condition. Both measurements can be used for the successful design of a sleepiness detection countermeasure device.

  16. Daytime sleepiness and sleep quality among Malaysian medical students.

    Science.gov (United States)

    Zailinawati, A H; Teng, C L; Chung, Y C; Teow, T L; Lee, P N; Jagmohni, K S

    2009-06-01

    Poor sleep quality and daytime somnolence is reported to be associated with cardiovascular events, road traffic accident, poor academic performance and psychological distress. Some studies documented that it is prevalent in most populations but its frequency among medical students has not been documented in Malaysia. This is a self-administered questionnaire survey of medical students from International Medical University, Malaysia. Daytime sleepiness of medical students was assessed using Epworth Sleepiness Scale (ESS). Student scoring ESS > 11 was regarded as having excessive daytime sleepiness. Psychological distress was measured using 12-item General Health Questionnaire (GHQ-12). A total of 799 medical students participated in this survey (response rate 69.5%). Daytime sleepiness occurred in 35.5%, psychological distress was present in 41.8% and 16.1% reported bad sleep quality. Daytime sleepiness was significantly more common among the clinical students, those with self-reported bad sleep quality and psychological distress; but unrelated to the number of hours sleep at night. We have documented high prevalence of daytime sleepiness, poor sleep quality and psychological distress. Higher frequency among clinical students and the significant relationship with psychological distress suggest possible link to the stressful clinical training.

  17. 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

  18. The Role of MAPK in Drug-Induced Kidney Injury

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    Hilary Cassidy

    2012-01-01

    Full Text Available This paper focuses on the role that mitogen-activated protein kinases (MAPKs play in drug-induced kidney injury. The MAPKs, of which there are four major classes (ERK, p38, JNK, and ERK5/BMK, are signalling cascades which have been found to be broadly conserved across a wide variety of organisms. MAPKs allow effective transmission of information from the cell surface to the cytosolic or nuclear compartments. Cross talk between the MAPKs themselves and with other signalling pathways allows the cell to modulate responses to a wide variety of external stimuli. The MAPKs have been shown to play key roles in both mediating and ameliorating cellular responses to stress including xenobiotic-induced toxicity. Therefore, this paper will discuss the specific role of the MAPKs in the kidney in response to injury by a variety of xenobiotics and the potential for therapeutic intervention at the level of MAPK signalling across different types of kidney disease.

  19. 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

  20. PTTG1 attenuates drug-induced cellular senescence.

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    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.

  1. 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.

  2. 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

  3. 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.

  4. 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. PMID:25018659

  5. Non-linear analysis for the sleepy drivers problem.

    Science.gov (United States)

    Chouvarda, Ioanna; Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Koufogiannis, Dimitris; Bekiaris, Evaggelos; Maglaveras, Nikos

    2007-01-01

    The problem addressed in this work is sleepiness during driving, which often leads to accidents in the streets. Experiments with sleepy drivers took place and the EEG data were analysed in terms of non-linear methods. Sample entropy and phase synchronization variations were investigated within the signal sections corresponding to "driving events", i.e. driving mistakes or loss of control, as well as to periods of drowsiness and sleepiness, as compared to the periods of normal driving. Decreased sample entropy, indicating loss of complexity, and an increased phase synchronisation have been found in the preliminary study presented. The results are encouraging towards developing an alerting system for predicting and preventing driving accidents.

  6. 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.

  7. 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.

  8. HLA Association with Drug-Induced Adverse Reactions

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    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. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

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    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.

  10. 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.

  11. First report of drug-induced esophagitis by deferasirox.

    Science.gov (United States)

    Yoshikawa, Takeshi; Hara, Takeshi; Araki, Hiroshi; Tsurumi, Hisashi; Oyama, Masami; Moriwaki, Hisataka

    2012-06-01

    Deferasirox is a new oral iron chelator used to treat transfusional iron overload. We describe a case of a 79-year-old man with myelodysplastic syndrome (MDS) who developed esophagitis induced by deferasirox. He repeatedly received multiple red blood cell transfusions after a diagnosis of MDS. Two years after starting red blood cell transfusions, he was diagnosed with iron overload, and was then started on deferasirox at 1 g/day with about 400 ml of water. He was admitted to our institution because he was unable to swallow his own saliva 1 month after starting deferasirox. Esophagogastroendoscopy revealed white-coated mucosa covering the entire esophagus. A component analysis of biopsy specimens using high-performance liquid chromatography identified deferasirox. Symptoms resolved within about 2 weeks after discontinuing deferasirox, and repeated endoscopy showed marked improvement of esophagitis after 1 month. Re-administration of deferasirox was not attempted. Unfortunately, the patient died due to pneumonia 6 months after administration of deferasirox was started. This is the first report of drug-induced esophagitis associated with deferasirox.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Administration of Drug Induce Liver Injury to the Inpatients with Liver Disease

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    Sindy E. Cinthya

    2012-06-01

    Full Text Available Drug induced liver injury is a serious human health problems. Pre-existing liver diseases are risk factor of liver injury by the drugs. The study was conducted to evaluate the use of drug induced liver injury in patients hospitalized with liver disease at one hospital in Kota Tasikmalaya. Informations were collected retrospectively in the period 2010-2011 from the patient’s medical record. A total of 52 patients research subjects were discovered 50 patients (96% using drug induced liver injury and 2 patients (4% did not use it. Drug induced liver injury most widely used were ranitidine (31.3%, ceftriaxone (23.1%, and paracetamol (16.4%. Level of the DILI usage in patient with liver disease was relative high (96%. Further research is needed to determine the effect of the drug induced liver injury to liver injury.

  15. Ecological momentary assessment of fatigue, sleepiness, and exhaustion in ESKD.

    Science.gov (United States)

    Abdel-Kader, Khaled; Jhamb, Manisha; Mandich, Lee Anne; Yabes, Jonathan; Keene, Robert M; Beach, Scott; Buysse, Daniel J; Unruh, Mark L

    2014-02-06

    Many patients on maintenance dialysis experience significant sleepiness and fatigue. However, the influence of the hemodialysis (HD) day and circadian rhythms on patients' symptoms have not been well characterized. We sought to use ecological momentary assessment to evaluate day-to-day and diurnal variability of fatigue, sleepiness, exhaustion and related symptoms in thrice-weekly maintenance HD patients. Subjects used a modified cellular phone to access an interactive voice response system that administered the Daytime Insomnia Symptom Scale (DISS). The DISS assessed subjective vitality, mood, and alertness through 19 questions using 7- point Likert scales. Subjects completed the DISS 4 times daily for 7 consecutive days. Factor analysis was conducted and a mean composite score of fatigue-sleepiness-exhaustion was created. Linear mixed regression models (LMM) were used to examine the association of time of day, dialysis day and fatigue, sleepiness, and exhaustion composite scores. The 55 participants completed 1,252 of 1,540 (81%) possible assessments over the 7 day period. Multiple symptoms related to mood (e.g., feeling sad, feeling tense), cognition (e.g., difficulty concentrating), and fatigue (e.g., exhaustion, feeling sleepy) demonstrated significant daily and diurnal variation, with higher overall symptom scores noted on hemodialysis days and later in the day. In factor analysis, 4 factors explained the majority of the observed variance for DISS symptoms. Fatigue, sleepiness, and exhaustion loaded onto the same factor and were highly intercorrelated. In LMM, mean composite fatigue-sleepiness-exhaustion scores were associated with dialysis day (coefficient and 95% confidence interval [CI] 0.21 [0.02 - 0.39]) and time of day (coefficient and 95% CI 0.33 [0.25 - 0.41]. Observed associations were minimally affected by adjustment for demographics and common confounders. Maintenance HD patients experience fatigue-sleepiness-exhaustion symptoms that demonstrate

  16. 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.

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

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    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.

  18. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  19. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.

    2011-01-01

    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  20. Validation of the Arabic version of the Epworth Sleepiness Scale

    Directory of Open Access Journals (Sweden)

    Anwar E. Ahmed

    2014-12-01

    Conclusions: The study shows that the ArESS is a valid and reliable tool that can be used in Arabic-speaking populations to measure daytime sleepiness. The current study has shown that the average ESS score of healthy Arabian subjects is significantly higher than in Western cultures.

  1. 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.

  2. Sleep, Sleepiness and Medical College Students: A Comparative ...

    African Journals Online (AJOL)

    Arun Chutani

    tweak, and build upon the work non-commercially, as long as the author is credited and the new ... sleep duration, daytime sleepiness and sleep associated problems in 271 students of medical and paramedical course. ... Annals of Medical and Health Sciences Research | March-April 2017 | Vol 7 | Issue 2 |. There can be a ...

  3. 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.

  4. Sleep, Sleepiness and Medical College Students: A Comparative ...

    African Journals Online (AJOL)

    Subjects and Methods: Validated questionnaires (PSQI, ESS and Sleep 50) along with sleep diary and demographic sheet were used to study sleep duration, daytime sleepiness and sleep associated problems in 271 students of medical and paramedical course. Results: Study group included MBBS (76.4%, 207/271) and ...

  5. 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

  6. Use of Arotinolol Pharmacotherapy to Treat Drug-induced Tremor: A Report of Three Cases.

    Science.gov (United States)

    Lee, D B; Woo, Y S; Bahk, W M

    2015-07-01

    The aim of the present study is to demonstrate the effect of arotinolol on drug-induced tremor in psychiatric patients. This is a case study of three psychiatric patients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of major depressive disorder who were treated in inpatient or outpatient psychiatric settings with antidepressant or antipsychotics. Patients developed tremor. Arotinolol was started to treat the tremor. Drug-induced tremor almost resolved completely. No adverse effects were observed. We have presented a case series of drug-induced tremors that responded well to treatment with arotinolol, which appears to be a safe and well-tolerated drug in the dose ranges used. The possible utility of arotinolol to treat drug-induced tremor deserves attention and further investigation. © Georg Thieme Verlag KG Stuttgart · New York.

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

    OpenAIRE

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

    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 Th...

  8. Sleep, sleepiness and motor vehicle accidents: a national survey.

    Science.gov (United States)

    Gander, Philippa H; Marshall, Nathaniel S; Harris, Ricci B; Reid, Papaarangi

    2005-02-01

    To assess the role of sleep-related factors, ethnicity and socioeconomic deprivation in self-reported motor vehicle accidents while driving, after controlling for gender, age and driving exposure. Mail survey to a random electoral roll sample of 10,000 people aged 30-60 years, stratified by age decades and ethnicity (71% response rate). The analytical sample included 5,534 current drivers (21.6% Maori men, 21.2% Maori women, 30% non-Maori men, 27.2% non-Maori women). Multiple logistic regression analyses revealed the following independent risk factors for accident involvement while driving (last three years): being younger; higher average weekly driving hours; never/rarely getting enough sleep (OR=1.26, 95% CI 1.06-1.49); reporting any chance of dozing in a car while stopped in traffic (Epworth Sleepiness Scale question 8, OR=1.52, 95% CI 1.15-2.02); and among women, being non-Maori. Total Epworth score was not significantly related to reported accident involvement. Chronic sleep restriction, and any likelihood of dozing off at the wheel of a motor vehicle, were significant independent predictors of self-reported involvement in all types of motor vehicle accidents, not only those identified as fatigue-related. The Epworth Sleepiness Scale alone is not a reliable clinical tool for identifying individuals at higher risk of crashes. Factors relating to chronic sleepiness were as important as established demographic risk factors for self-reported motor vehicle accident involvement among 30-60 year-old drivers. The findings reinforce the need for multi-faceted campaigns to reduce sleepy driving.

  9. 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).

  10. 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...

  11. Sleepiness in a Population of Italian Shift-work Policemen

    Science.gov (United States)

    2000-03-01

    population underwent a second investigation on sleep studied) a pathological level of sleepiness disturbances by means of an assisted was found...disturbances but the between group narcolepsy (three questions regarding the differences did not result statistically presence of cataplexy, sleep paralysis ...Adaptability to Irregular Rest-Work Rhythms/Status of the Use of Drugs in Sleep -Wakefulness Management [les Differences entre individus concernant les

  12. 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.

  13. 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

  14. Relationship between snoring sound intensity and sleepiness in patients with obstructive sleep apnea.

    Science.gov (United States)

    Nakano, Hiroshi; Furukawa, Tomokazu; Nishima, Sankei

    2008-12-15

    Subjectively assessed snoring and sleepiness are known to be related. However, no evidence supporting the usefulness of snoring measurements exists. We examined whether the objectively measured snoring intensity was correlated with sleepiness. The records of 515 patients who underwent polysomnography for suspected obstructive sleep apnea were retrospectively reviewed. Subjective sleepiness was assessed using the Epworth sleepiness scale (ESS). Snoring intensity was assessed using the highest one percentile ambient sound pressure level (L1) attained while asleep during polysomnography. L1 was correlated with ESS in apneic patients with an apnea-hypopnea index (AHI) > or =15 (r = 0.38, p snoring, and nasal obstruction symptoms as determinants for the ESS. L1 was correlated with the mean pulse rate during polysomnography but not with sleep fragmentation variables after adjustment for the AHI. The measured snoring intensity was independently related to sleepiness in apneics. Snoring intensity may explain part of sleepiness that cannot be fully explained by ordinary polysomnographic variables.

  15. How sleep and mental disorders are related to complaints of daytime sleepiness.

    Science.gov (United States)

    Ohayon, M M; Caulet, M; Philip, P; Guilleminault, C; Priest, R G

    Daytime sleepiness is widespread and has negative impacts on the public sector. To ascertain the incidence and prevalence of daytime sleepiness and associated risk factors in the general population. In 1994, a representative sample of the non-institutionalized British population aged 15 years or older was interviewed via telephone using an expert computer-assisted program designed to facilitate surveys of this type (Sleep-Eval, M. M. Ohayon, Montreal, Quebec). Subjects were classified into 3 groups based on the severity of their daytime sleepiness. We completed 4972 interviews (acceptance rate, 79.6%). Severe daytime sleepiness was reported in 5.5% (95% confidence interval, 4.9%-6.1%) of the sample, and moderate daytime sleepiness in another 15.2% (95% confidence interval, 14.2%-16.2%). Associated factors with severe daytime sleepiness included female sex, middle age, napping, insomnia symptoms, high daily caffeine consumption, breathing pauses or leg pain in sleep, depressive disorder (based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria), falling asleep while reading or watching television, and motor vehicle crashes or accidents involving use of machinery. Moderate daytime sleepiness was associated with female sex, napping, insomnia symptoms, arthritis or heart disease, and gross motor movements during sleep. It is likely that daytime sleepiness deleteriously affects work activities, social and/or marital life, and exhibits a negative socioeconomic impact. In addition, the risk of a motor vehicle crash appears to be higher in this specific population: twice as many subjects operating a motor vehicle or using machine tools reported having a crash or accident, respectively, in the previous year in the groups with severe daytime sleepiness or moderate daytime sleepiness than did the general population with no daytime sleepiness. The high prevalence rates of daytime sleepiness and multiplicity of related factors mandate further

  16. 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.

  17. Effects of context on sleepiness self-ratings during repeated partial sleep deprivation.

    Science.gov (United States)

    Akerstedt, Torbjörn; Kecklund, Göran; Axelsson, John

    2008-04-01

    Ratings of subjective sleepiness are often used in laboratory and field studies of sleep loss and shifted sleep hours. Some studies suggest that such ratings might fail to reflect sleepiness as shown in physiology or performance. One reason for this may be the influence of the context of the rating. Social interaction or physical activity may mask latent sleepiness. The present study attempted to approach this question. Nine subjects participated in a partial sleep-deprivation experiment (five days of 4 h of time in bed [TIB]), preceded by two baseline days (8 h TIB) and followed by three recovery days (8 h TIB). Sleepiness was self-rated on the Karolinska Sleepiness Scale (KSS; scores of 1-9) after a period of relaxation, after a reaction-time test, and after 30 min of free activities. The results showed a strong increase in subjective sleepiness during sleep restriction and a significant difference between conditions. Free activity reduced the self-rated subjective sleepiness by 1.1 KSS units compared to the level of sleepiness self-rated at the end of the reaction-time test. Thus, the results of this study indicate that the context of a sleepiness rating affects the outcome of the rating.

  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. 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.

  20. Clinical and polysomnographic characteristics of excessive daytime sleepiness in children.

    Science.gov (United States)

    Lee, Jiwon; Na, Geonyoub; Joo, Eun Yeon; Lee, Munhyang; Lee, Jeehun

    2017-12-01

    This study aimed to delineate the clinical and polysomnography (PSG) characteristics of sleep disorders in children with excessive daytime sleepiness (EDS). Between February 2002 and June 2015, 622 pediatric patients with EDS were evaluated with overnight PSG and the Multiple Sleep Latency Test at the Samsung Medical Center. The medical records; questionnaire responses about depression, sleepiness, sleep habits; and sleep study data of 133 patients without obstructive sleep apnea (OSA) were reviewed retrospectively. The patients (63 girls, 70 boys) slept for an average of 7 h 30 min and 8 h 44 min on weekdays and weekends, respectively. The mean Epworth Sleepiness Scale score was 11.01 ± 4.09 and did not differ significantly among sleep disorders. Among the 102 patients who completed the depression questionnaire, 53 showed depressive feelings, which were moderate or severe in 39, with no significant differences among specific sleep disorders. Thirty-four patients exhibited normal PSG results. Seventeen of them were concluded as not having any sleep disorders, and the others as having delayed sleep phase disorder (DSPD). Narcolepsy (n = 78) was the most common disorder, followed by DSPD (n = 17) and idiopathic hypersomnia (n = 12). Pediatric patients with EDS had various sleep disorders and some did not have any sleep disorder despite EDS. More than half the patients with EDS showed depressive feelings affecting their daily lives. For pediatric patients with EDS, a systematic diagnostic approach including questionnaires for sleep habits and emotion and PSG is essential for accurate diagnosis and treatment.

  1. 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.

  2. 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.

  3. Correntropy measures to detect daytime sleepiness from EEG signals.

    Science.gov (United States)

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

    2014-10-01

    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).

  4. 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

  5. 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

  6. Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization

    Directory of Open Access Journals (Sweden)

    Ioanna A. Comstock

    2015-01-01

    Full Text Available Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.

  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. Sleep patterns and sleepiness of working college students.

    Science.gov (United States)

    Teixeira, Liliane; Lowden, Arne; da Luz, Andrea Aparecida; Turte, Samantha Lemos; Valente, Daniel; Matsumura, Roberto Jun; de Paula, Leticia Pickersgill; Takara, Meire Yuri; Nagai-Manelli, Roberta; Fischer, Frida Marina

    2012-01-01

    The double journey (work and study) may result or aggravate health problems, including sleep disturbances, as observed in previous studies with high school students. The aim of this study is to analyze the sleep-wake cycle and perceived sleepiness of working college students during weekdays. Twenty-three healthy college male students, 21-24 years old, working during the day and attending classes in the evening, participated in this study. During five consecutive days, the students filled out daily activities logs and wore actigraphs. Mean sleeping time was lower than 6 hours per night. No significant differences were observed in the sleep-wake cycle during the weekdays. The observed lack of changes in the sleepwake cycle of these college students might occur as participants were not on a free schedule, but exposed to social constraints, as was the regular attendance to evening college and day work activities. Sleepiness worsened over the evening school hours. Those results show the burden carried by College students who perform double activities - work and study.

  9. 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.

  10. 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...

  11. Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea

    Directory of Open Access Journals (Sweden)

    Han-Ki Park

    2017-10-01

    Conclusions: Platinum compounds are the most commonly reported causative agents of in-hospital drug-induced anaphylaxis. Older age ≥70 years and drugs such as iodinated contrast media and aminosteroid NMBA are related with high risk of anaphylactic shock.

  12. Unraveling cellular pathways contributing to drug-induced liver injury by dynamical modeling

    NARCIS (Netherlands)

    Kuijper, I.A.; Yang, H.; Water, van de B.; Beltman, J.B.

    2017-01-01

    Introduction: Drug-induced liver injury (DILI) is a significant threat to human health and a major problem in drug development. It is hard to predict due to its idiosyncratic nature and which does not show up in animal trials. Hepatic adaptive stress response pathway activation is generally observed

  13. 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.

  14. 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....

  15. 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

  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 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.

  18. Nocturnal frontal lobe epilepsy presenting as excessive daytime sleepiness

    Directory of Open Access Journals (Sweden)

    Jocelyn Y Cheng

    2013-01-01

    Full Text Available Excessive daytime sleepiness (EDS is common in the general population. Etiologies include insufficient sleep and primary sleep disorders. Due to its high prevalence, physicians often overlook EDS as a significant problem. However, EDS may also be the presenting symptom of seizures, in particular Nocturnal Frontal Lobe Epilepsy (NFLE. Due to the clinical similarity between the nocturnal behaviors of NFLE and parasomnias, and poor patient-related history, NFLE remains a challenging diagnosis. We report the case of a patient with NFLE who presented with a primary complaint of EDS, and discuss the differential diagnosis and evaluation of patients with EDS associated with nocturnal behaviors. In the context of a patient presenting with EDS and stereotyped nocturnal events, clinical suspicion should be high for NFLE.

  19. 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.

  20. 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).

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Daytime Sleepiness: Associations with Alcohol Use and Sleep Duration in Americans

    Directory of Open Access Journals (Sweden)

    Subhajit Chakravorty

    2014-01-01

    Full Text Available The aim of the current analysis was to investigate the relationship of daytime sleepiness with alcohol consumption and sleep duration using a population sample of adult Americans. Data was analyzed from adult respondents of the National Health and Nutritional Examination Survey (NHANES 2007-2008 (N=2919 using self-reported variables for sleepiness, sleep duration, and alcohol consumption (quantity and frequency of alcohol use. A heavy drinking episode was defined as the consumption of ≥5 standard alcoholic beverages in a day. Logistic regression models adjusted for sociodemographic variables and insomnia covariates were used to evaluate the relationship between daytime sleepiness and an interaction of alcohol consumption variables with sleep duration. The results showed that daytime sleepiness was reported by 15.07% of the subjects. In univariate analyses adjusted for covariates, an increased probability of daytime sleepiness was predicted by decreased log drinks per day [OR = 0.74 (95% CI, 0.58–0.95], a decreased log drinking frequency [0.90 (95% CI, 0.83–0.98], and lower sleep duration [OR = 0.75 (95% CI, 0.67–0.84]. An interaction between decreased sleep duration and an increased log heavy drinking frequency predicted increased daytime sleepiness (P=0.004. Thus, the effect of sleep duration should be considered when evaluating the relationship between daytime sleepiness and heavy drinking.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Snoring, daytime sleepiness, and incident cardiovascular disease in the health, aging, and body composition study.

    Science.gov (United States)

    Endeshaw, Yohannes; Rice, Thomas B; Schwartz, Ann V; Stone, Katie L; Manini, Todd M; Satterfield, Suzanne; Cummings, Steven; Harris, Tamara; Pahor, Marco

    2013-11-01

    To examine the association between snoring and incident cardiovascular disease (CVD). This is a prospective study in which community dwelling older adults were evaluated at baseline, and followed up for an average of 9.9 years. Data on snoring, daytime sleepiness, as well as demographic and clinical characteristics of study participants was collected at baseline, and participants were followed up every six months for an average of 9.9 years. Based on snoring and sleepiness status, 4 groups of participants were created: (1) No Snoring, No Sleepiness; (2) No Snoring, Sleepiness; (3) Snoring, No Sleepiness; (4) Snoring, Sleepiness. Incident CVD was defined as a diagnosis of myocardial infarction, angina pectoris, or congestive heart failure that resulted in overnight hospitalization during the follow-up period. Cox proportional hazard was used to estimate the risk of incident cardiovascular disease during follow-up by baseline snoring and sleepiness status. A total of 2,320 participants with a mean age of 73.6 (2.9) years at baseline were included in the analysis. Fifty-two percent were women, and 58% were white. A total of 543 participants developed CVD events during the follow-up period. Participants who reported snoring associated with daytime sleepiness had significantly increased hazard ratio for CVD events (HR = 1.46 [1.03-2.08], P = 0.035) after adjusting for demographic and clinical confounding factors. The results suggest that self-reported snoring and daytime sleepiness status are associated with an increased risk of future cardiovascular disease among older adults.

  6. 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.

  7. 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.

  8. Fatal drug-induced immune hemolytic anemia due to cefotetan; A case study

    Directory of Open Access Journals (Sweden)

    Perkins Jim

    2008-01-01

    Full Text Available A case is described here of drug-induced immune hemolytic anemia (DIIHA due to cefotetan administered to a post-partum woman who received the drug for infection prophylaxis at the time of caesarean section. Renewed fatal hemolysis occurred when the drug was given a second time 12 days after the first dose. The initial immunohematologic findings included a positive direct antiglobulin test (DAT due to IgG and complement coating of the patient′s RBCs as well as an eluate that did not react with RBCs in the absence of drug. The antibody was drug-dependent, reacting with both drug-coated RBCs as well as when the drug was added to a mixture of her serum and donor RBCs. Cefotetan has been a common cause of this uncommon problem. The clinical features of cefotetan DIIHA, classification of drug-induced antibodies, and the differential diagnosis of a positive DAT are briefly discussed.

  9. Episcleritis Related to Drug-Induced Lupus Erythematosus following Infliximab Therapy: A Case Report

    OpenAIRE

    Chatziralli, Irini P.; Kanonidou, Evgenia; Chatzirallis, Alexandros; Dimitriadis, Prodromos; Keryttopoulos, Petros

    2011-01-01

    Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. Herein, we describe a patient with distinct clinical manifestations of anti-TNF-associated DILE related to infliximab therapy. The patient exhibited clinical and laboratory findings of lupus-like illnesses as well as ocular disorders, such as episcleritis. The main message is that the symptoms of DILE should not be over...

  10. Glucuronidation of Drugs and Drug-Induced Toxicity in Humanized UDP-Glucuronosyltransferase 1 Mice

    OpenAIRE

    Kutsuno, Yuki; Itoh, Tomoo; Tukey, Robert H.; Fujiwara, Ryoichi

    2014-01-01

    UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that catalyze glucuronidation of various drugs. Although experimental rodents are used in preclinical studies to predict glucuronidation and toxicity of drugs in humans, species differences in glucuronidation and drug-induced toxicity have been reported. Humanized UGT1 mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice) were recently developed. In this study, acyl-glu...

  11. Sjögren-like pluriglandular exocrine insufficiency after drug-induced toxic epidermal necrolysis.

    OpenAIRE

    Sabán, J.; Pais, J. R.; Rodríguez, J. L.; Boixeda, D.

    1991-01-01

    We present the case of a patient that progressively developed xerophthalmia, xerostomia, cutaneous xerosis and exocrine pancreatic insufficiency 3 months after metamizole-induced toxic epidermal necrolysis. Though the association of Sjögren's syndrome and exocrine pancreatic impairment is well established, the Sjögren-like syndrome after drug-induced toxic epidermal necrolysis in association with such a wide exocrine glandular insufficiency has not been previously described, to our knowledge.

  12. Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints

    OpenAIRE

    Kim, Eunyoung; Nam, Hojung

    2017-01-01

    Background Drug-induced liver injury (DILI) is a critical issue in drug development because DILI causes failures in clinical trials and the withdrawal of approved drugs from the market. There have been many attempts to predict the risk of DILI based on in vivo and in silico identification of hepatotoxic compounds. In the current study, we propose the in silico prediction model predicting DILI using weighted molecular fingerprints. Results In this study, we used 881 bits of molecular fingerpri...

  13. The Clinical Course of a Drug-induced Acute Dystonic Reaction in the Emergency Room

    Directory of Open Access Journals (Sweden)

    Massimo Marano

    2016-12-01

    Full Text Available Background: Acute dystonic reactions following the administration of safe, reliable drugs can occur and must be promptly recognized and treated in the emergency room.Phenomenology Shown: The entire clinical course of an acute dystonic reaction due to metoclopramide, from early motor signs to full-blown clinical symptoms and resolution.Educational Value: Providing elements for early recognition of a drug-induced movement disorder phenomenology.   

  14. Drug-Induced Myocardial Infarction Secondary to Coronary Artery Spasm in Teenagers and Young Adults

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    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.

  15. 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.

  16. Management of drug-induced movement disorders in psychiatry: an update

    Directory of Open Access Journals (Sweden)

    Sekh Afrar Alam

    2016-07-01

    Full Text Available Drug-induced movement disorders (DIMD represent a variety of iatrogenic and clinically distinct movement disorders, including akathisia, tardive dyskinesia, dystonia, and Parkinsonism. DIMD remain a significant burden especially among certain patient populations receiving psychotropic medication. Knowledge of DIMDs will allow clinicians and healthcare professionals to better identify and manage patients with these conditions. Here we discuss the important features and current practical management steps of different types of DIMD in psychiatry.

  17. 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.

  18. Evening chronotype and sleepiness predict impairment in executive abilities and academic performance of adolescents.

    Science.gov (United States)

    Cohen-Zion, Mairav; Shiloh, Elisheva

    2018-01-01

    The study aim was to better understand sleep and sleep-related factors affecting everyday executive capacities and academic performance among healthy adolescents. A cross-sectional survey on sleep, phase preference, academic performance and executive functions of high-school students was conducted. Female gender, grade status, sleepiness and evening chronotype accounted for approximately 25-30% of the variance in daily executive ability. Sleep duration was a weak predictor of executive skills. Lower school grades were associated with increased sleepiness, evening preference and poorer executive skills. These findings support the need for health education on ways to attenuate sleepiness and delayed phase in this population.

  19. 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

    2007-01-01

    Study Objectives: 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. Design: A cross-sectional survey of students from 7 schools in 4 cities of Argentina. Measurements: 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. Participants: The sample included 2,884 students (50% males; age: 13.3 ± 1.5 years) Results: Response rate was 85%; 678 cases were excluded due to missing data. Half the students slept academic performance. Citation: Perez-Chada D; Perez-Lloret S; Videla AJ; Cardinali D; Bergna MA; Fernández-Acquier M; Larrateguy L; Zabert GE; Drake C. Sleep disordered breathing and daytime sleepiness are associated with poor academic performance in teenagers. A study using the pediatric daytime sleepiness scale (PDSS). SLEEP 2007;30(12):1698-1703. PMID:18246979

  20. Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats

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    Xin Liu

    2017-04-01

    Full Text Available The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats.

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

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    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.

  2. 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

  3. Using saliva nitrite and nitrate levels as a biomarker for drug induced gingival overgrowth

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    Erkan eSukuroglu

    2015-12-01

    Full Text Available Aim: Drug-induced gingival overgrowth has a multifactorial nature and the pathogenesis is still uncertain. It has been suggested that Nitric Oxide (NO might play a role in the pathogenesis of drug-induced gingival overgrowth due to the contribution of NO to immune response and matrix degradation. NO levels in biological fluids have been used as a diagnostic biomarker in many diseases. The aim of this study is to determine whether NO levels in plasma, saliva and gingival crevicular fluid (GCF can serve as a potential biomarker for the evaluation of drug-induced gingival overgrowth risk. Material and Methods: A total of 104 patients, receiving cyclosporine A (n=35, phenytoin (n=25, nifedipine (n=26 or diltiazem (n=18 participated in the study. The amount of gingival overgrowth was evaluated with two indices and was given as percentage. Periodontal clinical parameters including plaque index (PI, gingival index (GI, gingival bleeding time index (GBTI and probing depth (PD were also assessed. Saliva, GCF and plasma samples were obtained from each participants. Nitrite and nitrate levels in saliva, GCF and plasma were analyzed by Griess reagent. Results: Salivary nitrite and nitrate levels in responders were significantly higher than those in non-responders in only phenytoin group (p˂0.05. Nitrite and nitrate levels of gingival crevicular fluid and plasma did not significantly differ between responders and non-responders in all study groups (p˃0.05. Salivary nitrite levels exhibited a significant correlation with PD, GBTI, severity of gingival overgrowth (%GO and GCF volume (p˂0.05. Additionally, a strong positive correlation was detected between saliva and plasma nitrate levels (p˂0.005. However, both nitrite and nitrate levels in GCF and plasma demonstrated no significant correlation with clinical parameters, GO severity and GCF volume (p˃0.05.Conclusion: Salivary nitrite and nitrate levels could be used as periodontal disease biomarkers in

  4. 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).

  5. Social jetlag affects subjective daytime sleepiness in school-aged children and adolescents: A study using the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J).

    Science.gov (United States)

    Komada, Yoko; Breugelmans, Raoul; Drake, Christopher L; Nakajima, Shun; Tamura, Norihisa; Tanaka, Hideki; Inoue, Shigeru; Inoue, Yuichi

    2016-01-01

    The aim of this study was to elucidate the level of daytime sleepiness in Japanese school-aged children and adolescents, and to examine associated factors including sleep loss and social jetlag using the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J). After the linguistic validation of the PDSS-J with a multi-step translation methodology, consisting of forward translation, back translation, expert review and cognitive debriefing interviews, we conducted a psychometric validation for 492 students aged 11-16 years (46.7% boys) of public elementary school, junior high school and high school, using the PDSS-J, the Karolinska Sleepiness Scale (KSS), and bedtimes and wake-up times on school days and free days. Internal consistency (Cronbach's alpha) of the PDSS-J was 0.77, and the test-retest reliability demonstrated by the intraclass coefficient was 0.88. Multivariate logistic regression analysis revealed that both short sleep duration and social jetlag were identified as factors associated with daytime sleepiness, after adjustment for age and sex. PDSS-J scores were significantly higher in the group with large social jetlag with or without sufficient sleep duration than in the group with sufficient sleep duration and small social jetlag. The PDSS-J is an important tool for assessing daytime sleepiness, given its ease of administration and robust psychometric properties. The impact of not only sleep loss but also social jetlag on daytime sleepiness among school-aged children and adolescents must be fully taken into account.

  6. 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.

  7. Trading While Sleepy? Circadian Mismatch and Excess Volatility in a Global Experimental Asset Market

    OpenAIRE

    Dickinson, David L.; Chaudhuri, Ananish; Greenaway-McGrevy, Ryan

    2017-01-01

    Traders in global markets operate at different local times-of-day. Suboptimal times-of-day may produce sleepiness due to daily variations in sleep/wake patterns and possibly also increased accumulation of hours awake. Global asset markets imply significantly increased heterogeneity in circadian timing, and likely sleepiness, of trader decisions compared to localized markets. We examine these factors by administering single-location and global sessions of an online asset market experiment that...

  8. Excessive Daytime Sleepiness and Epilepsy: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Andre S. Giorelli

    2013-01-01

    Full Text Available Background. Sleep complaints are common in patients with epilepsy (PWE. Excessive daytime sleepiness (EDS is one of the most reported complaints and its impact is still a matter of debate. Objective. Evaluate the relationship between EDS and epilepsy, with emphasis on prevalence, assessment, and causes. Methods. A systematic review on PubMed database in the last 10 years (2002 to 2012. The search returned 53 articles and 34 were considered relevant. After citation analysis, 3 more articles were included. Results. Most studies were cross-sectional and questionnaire based. 14 papers addressed EDS as the primary endpoint. 14 adult and 3 children studies used subjective and objective analysis as methodology. The number of studies increased throughout the decade, with 21 in the last 5 years. Adult studies represent almost three times the number of children studies. EDS prevalence in PWE varies from 10 to 47.5%. Prevalence was higher in developing countries. Conclusion. EDS seems to be related more frequently to undiagnosed sleep disorders than to epilepsy-related factors, and although it affects the quality of life of PWE, it can be improved by treating comorbid primary sleep disorders.

  9. [Excessive daytime sleepiness and risk for obstructive sleep apnea in the public transport drivers].

    Science.gov (United States)

    Minarowski, Łukasz; Chwieśko-Minarowska, Sylwia; Czaban, Marcin; Mickiewicz, Magdalena; Kozakiewicz, Natalia; Kuryliszyn-Moskal, Anna; Chyczewska, Elżbieta

    2015-01-01

    Obstructive sleep apnea (OSA) is a set of symptoms related to the increased upper airways resistance during sleep (due to pharyngeal walls collapse) leading to intermittent airflow obstruction in the lungs. One of the most severe OSA symptoms is excessive daytime sleepiness. Sustained daytime sleepiness may impair cognitive functions and thus influence the everyday functioning of affected person. The aim of the study was to prospectively assess excessive daytime sleepiness and the risk for OSA in municipal bus drivers. The study was performed in a group of 103 men. The anonymous survey comprised Epworth Sleepiness Scale (ESS) for daytime sleepiness assessment and STOP-Bang Questionnaire (SBQ) for OSA risk assessment. In 43 (42%) respondents OSA risk was assessed as low, while moderate and high risk was observed in 55 (53%) and 5 (5%) drivers, respectively. Severe daytime sleepiness correlated positively with ESS results (r = 0.32; p < 0.05). In drivers with high OSA risk revealed in SBQ no correlation with high ESS was observed. In drivers with moderate and high OSA risk a sleep medicine specialist consultation with a consecutive diagnostic procedures is necessary. STOP-Bang Questionnaire and ESS are the fast tools to identify patients at increased risk for OSA. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

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

    Science.gov (United States)

    Lopes, Johnnatas Mikael; Dantas, Fabio Galvao; Medeiros, Jovany Luis Alves de

    2013-12-01

    To observe the relationship between Excessive Daytime Sleepiness (EDS) and the presence of risk factors for cardiovascular dysfunction, depression and obesity in the elderly. 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 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. 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.

  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. Thermophysiologic aspects of the three-process-model of sleepiness regulation.

    Science.gov (United States)

    Kräuchi, Kurt; Cajochen, Christian; Wirz-Justice, Anna

    2005-04-01

    The following overview reconsiders the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) from a thermophysiologic point of view. Our results gathered over the last decade indicate that the homeostatic aspect of sleepiness regulation (ie, buildup of sleepiness during wakefulness and its decay during sleep) is not related to the thermoregulatory system, whereas the two other processes of sleepiness regulation (ie, circadian and sleep inertia process) are clearly related to thermoregulation in humans. Distal skin temperature of hands and feet seems to be the crucial variable for the association between thermophysiology, sleepiness, and sleep. Increased distal skin temperature before a nocturnal sleep episode is a good predictor for short sleep-onset latency. The disappearance of sleep inertia after sleep or a nap episode shows very similar kinetics as distal vasoconstriction. Furthermore, relaxation-induced sleepiness (eg, after lying down, at lights-off, with thermal biofeedback training) also evokes an increase in distal skin temperatures. The reverse effect occurs at lights-on or a posture change from supine to standing, Therefore, in terms of thermophysiology, sleep inertia can be explained as the reverse of a relaxation process (ie, decrease in distal skin temperatures). Our results reinterpret the so-called "sleep-evoked" reduction of core body temperature as a consequence of relaxation-induced vasodilatation after lights-off. Sleep per se has no further thermoregulatory effect. Taken together, a thermophysiologic approach may provide a successful strategy to treat sleep-onset insomnia and alleviate sleep inertia.

  13. The relationship between subjective and objective sleepiness and performance during a simulated night-shift with a nap countermeasure.

    Science.gov (United States)

    Tremaine, Rebecca; Dorrian, Jill; Lack, Leon; Lovato, Nicole; Ferguson, Sally; Zhou, Xuan; Roach, Greg

    2010-12-01

    The aim of the present study was to investigate the relationship between perceived and actual sleepiness and performance during a simulated night-shift that included a 30-min night-nap as an on-duty sleepiness countermeasure. Twenty-four healthy young adults (nine males, fifteen females) participated in a repeated measures design comprising two experimental conditions: no night-nap and 30-min night-nap. Both groups were given a 2-h prophylactic afternoon sleep opportunity (1500-1700 h). Measures of subjective sleepiness (Stanford Sleepiness Scale, Karolinska Sleepiness Scale and Visual Analogue Scale), objective sleepiness (sleep latency tests), objective performance (Symbol-Digit Substitution Task) and reaction time (Psychomotor Vigilance Task) were taken before the night-nap (0230 h) and at several intervals post-nap. Time-series correlation analyses indicated that subjective sleepiness was less correlated with objective sleepiness and objective performance when participants were given a 30-min night-nap. However subjective sleepiness and reaction time performance was strongly correlated in both conditions, and there was no significant difference between the nap and no-nap conditions. Consistent with previous research, results of the present study indicate that subjective and objective indicators of sleepiness and performance may not always correspond, and this relationship may be reduced by the inclusion of a night-nap. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Drug-induced long QT syndrome and fatal arrhythmias in the intensive care unit.

    Science.gov (United States)

    Beitland, S; Platou, E S; Sunde, K

    2014-03-01

    Long QT syndrome (LQTS) is a genetic or acquired condition characterised by a prolonged QT interval on the surface electrocardiogram (ECG) and is associated with a high risk of sudden cardiac death because of polymorph ventricular tachyarrhythmia called Torsade de Pointes arrhythmia. Drug-induced LQTS can occur as a side effect of commonly used cardiac and non-cardiac drugs in predisposed patients, often with baseline QT prolongation lengthened by medication and/or electrolyte disturbances. Hospitalised patients often have several risk factors for proarrhythmic response, such as advanced age and structural heart disease. Patients in the intensive care unit (ICU) are particularly prone to develop drug induced LQTS because they receive several different intravenous medications. Additionally, they might have impaired drug elimination because of reduced kidney and/or liver function, and also drug-drug-interactions. The clinical symptoms and signs of LQTS range from asymptomatic patients to sudden death because of malignant arrhythmias, and it is therefore important to recognise the clinical characteristics and typical ECG changes. Treatment of acquired LQTS is mainly awareness, identification and discontinuation of QT prolonging drugs, in addition to eventually supplement of magnesium and potassium. Overdrive cardiac pacing is highly effective in preventing recurrences, and antiarrhythmic drugs should be avoided. Recent data suggest that QT prolongation is quite common in ICU patients and adversely affects patient mortality. Thus, high-risk patients should be sufficiently monitored, and the use of medications known to cause drug-induced LQTS might have to be restricted. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. 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

    2017-09-27

    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.

  16. Drug-induced premature chromosome condensation (PCC) protocols: cytogenetic approaches in mitotic chromosome and interphase chromatin.

    Science.gov (United States)

    Gotoh, Eisuke

    2015-01-01

    Chromosome analysis is a fundamental technique which is used in wide areas of cytogenetic study including karyotyping species, hereditary diseases diagnosis, or chromosome biology study. Chromosomes are usually prepared from mitotic cells arrested by colcemid block protocol. However, obtaining mitotic chromosomes is often hampered under several circumstances. As a result, cytogenetic analysis will be sometimes difficult or even impossible in such cases. Premature chromosome condensation (PCC) (see Note 1) is an alternative method that has proved to be a unique and useful way in chromosome analysis. Former, PCC has been achieved following cell fusion method (cell-fusion PCC) mediated either by fusogenic viruses (e.g., Sendai virus) or cell fusion chemicals (e.g., polyethylene glycol), but the cell fusion PCC has several drawbacks. The novel drug-induced PCC using protein phosphatase inhibitors was introduced about 20 years ago. This method is much simpler and easier even than the conventional mitotic chromosome preparation protocol use with colcemid block and furthermore obtained PCC index (equivalent to mitotic index for metaphase chromosome) is usually much higher than colcemid block method. Moreover, this method allows the interphase chromatin to be condensed to visualize like mitotic chromosomes. Therefore drug-induced PCC has opened the way for chromosome analysis not only in metaphase chromosomes but also in interphase chromatin. The drug-induced PCC has thus proven the usefulness in cytogenetics and other cell biology fields. For this second edition version, updated modifications/changes are supplemented in Subheadings 2, 3, and 4, and a new section describing the application of PCC in chromosome science fields is added with citation of updated references.

  17. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

    Science.gov (United States)

    Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

    2016-06-01

    Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Twelve cases of drug-induced blepharospasm improved within 2 months of psychotropic cessation

    Directory of Open Access Journals (Sweden)

    Emoto Y

    2011-06-01

    Full Text Available Yuko Emoto1, Hirofumi Emoto2, Eriko Oishi1, Syunichi Hikita1, Masato Wakakura11Division of Neuro-Ophthalmology, Inouye Eye Hospital, Tokyo; 2Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Graduate School of Medicine, Tokyo, JapanBackground: To determine whether psychotropic cessation in patients with drug-induced blepharospasm improves motor symptoms.Methods: In patients with drug-induced blepharospasm, we withdrew part or all of their psychotropic medication and assessed motor symptoms using the Jankovic rating scale (0 = none, 1 = noticeable, 2 = mild, 3 = moderate, 4 = severe at first presentation and after cessation.Results: Twelve patients (eleven women and one man, mean age 60.4 years were enrolled. Psychotropics were administered before the onset of blepharospasm in all patients. The mean duration of treatment with psychotropic medication was 47.3 (range 3–120 months. Jankovic rating scale at initial presentation was 3 in eleven patients and 2 in one patient. After cessation, blepharospasm started to improve in all cases within 2 months (average 3.9 weeks. While the effect of psychotropic cessation was variable, the symptoms eventually improved to more than 2 on the rating scale. Three of the twelve patients underwent a single botulinum neurotoxin injection and were withdrawn from therapy after cessation.Conclusion: Psychotropic drugs can cause blepharospasm in some cases. Clinicians should consider reducing psychotropic medication as far as possible in patients with blepharospasm taking these agents.Keywords: drug-induced, tardive, blepharospasm, antipsychotic, dose reduction, benzodiazepine

  19. "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

  20. "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

  1. Organization and logistics of drug-induced sleep endoscopy in a training hospital.

    Science.gov (United States)

    Benoist, L B L; de Vries, N

    2015-09-01

    Drug-induced sleep endoscopy (DISE) is a rapidly growing method to evaluate airway collapse in patients receiving non-CPAP therapies for sleep-disordered breathing (SDB). The growing number of DISEs has consequences for the organization of clinical protocols. In this paper we present our recent experiences with DISE, performed by an ENT resident, with sedation given by a nurse anesthetist, in an outpatient endoscopy setting, while the staff member/sleep surgeon discusses the findings and the recommended treatment proposal on the same day.

  2. Drug-induced acute pancreatitis: A rare manifestation of an incomplete “dapsone syndrome”

    Science.gov (United States)

    Das, Anup K.; Jawed, Qaiser

    2014-01-01

    Drug-induced acute pancreatitis (AP) is under-reported, and a large number of drugs are listed as offenders, but are often overlooked. Knowledge about the possible association of medications in causing AP is important, and needs a high index of suspicion, especially with drugs that have been reported to be the etiology only rarely. Dapsone, a commonly used drug, can cause various hypersensitivity reactions including AP collectively called “dapsone syndrome.” Here, we report dapsone-induced AP in a young man. Our case shows certain dissimilarities like associated acute renal failure and acute hemolysis not previously described. PMID:25097293

  3. Drug-induced acute pancreatitis: a rare manifestation of an incomplete "dapsone syndrome".

    Science.gov (United States)

    Das, Anup K; Jawed, Qaiser

    2014-01-01

    Drug-induced acute pancreatitis (AP) is under-reported, and a large number of drugs are listed as offenders, but are often overlooked. Knowledge about the possible association of medications in causing AP is important, and needs a high index of suspicion, especially with drugs that have been reported to be the etiology only rarely. Dapsone, a commonly used drug, can cause various hypersensitivity reactions including AP collectively called "dapsone syndrome." Here, we report dapsone-induced AP in a young man. Our case shows certain dissimilarities like associated acute renal failure and acute hemolysis not previously described.

  4. Episcleritis Related to Drug-Induced Lupus Erythematosus following Infliximab Therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Irini P. Chatziralli

    2011-01-01

    Full Text Available Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. Herein, we describe a patient with distinct clinical manifestations of anti-TNF-associated DILE related to infliximab therapy. The patient exhibited clinical and laboratory findings of lupus-like illnesses as well as ocular disorders, such as episcleritis. The main message is that the symptoms of DILE should not be overlooked, although sometimes other systematic conditions may underlie them. As a result, it is very important for the clinicians to evaluate the symptoms of DILE and manage appropriately these cases.

  5. 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...

  6. 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.

  7. Excessive sleepiness is predictive of cognitive decline in the elderly.

    Science.gov (United States)

    Jaussent, Isabelle; Bouyer, Jean; Ancelin, Marie-Laure; Berr, Claudine; Foubert-Samier, Alexandra; Ritchie, Karen; Ohayon, Maurice M; Besset, Alain; Dauvilliers, Yves

    2012-09-01

    To examine the association of sleep complaints reported at baseline (insomnia complaints and excessive daytime sleepiness (EDS)) and medication, with cognitive decline in community-dwelling elderly. An 8-yr longitudinal study. The French Three-City Study. There were 4,894 patients without dementia recruited from 3 French cities and having a Mini-Mental Status Examination (MMSE) score ≥ 24 points at baseline. Questionnaires were used to evaluate insomnia complaints (poor sleep quality (SQ), difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA)), EDS, and sleep medication at baseline. Cognitive decline was defined as a 4-point reduction in MMSE score during follow-up at 2, 4, and 8 yr. Logistic regression models were adjusted for sociodemographic, behavioral, physical, and mental health variables, and apolipoprotein E genotype. EDS independently increased the risk of cognitive decline (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.02-1.56), especially for those patients who also developed dementia during the follow-up period (OR = 1.39, 95% CI = 1.00-1.97). The number of insomnia complaints and DMS were negatively associated with MMSE cognitive decline (OR = 0.77, 95% CI = 0.60-0.98 for 3-4 complaints, OR = 0.81, 95% CI = 0.68-0.96, respectively). The 3 other components of insomnia (SQ, DIS, EMA) were not significantly associated with MMSE cognitive decline. Our results suggest that EDS may be associated independently with the risk of cognitive decline in the elderly population. Such results could have important public health implications because EDS may be an early marker and potentially reversible risk factor of cognitive decline and onset of dementia.

  8. 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.

  9. 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

    Study Objectives: To characterize and compare insomnia symptoms within two common phenotypes of Shift Work Disorder. Design: Observational laboratory and field study. Setting: Hospital sleep center. Participants: 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). Measurements: 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. Results: (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. Conclusions: 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. Citation: Gumenyuk V, Belcher R, Drake CL, Roth T. Differential sleep

  10. Sleep, sleepiness, fatigue, and performance of 12-hour-shift nurses.

    Science.gov (United States)

    Geiger-Brown, Jeanne; Rogers, Valerie E; Trinkoff, Alison M; Kane, Robert L; Bausell, R Barker; Scharf, Steven M

    2012-03-01

    Nurses working 12-h shifts complain of fatigue and insufficient/poor-quality sleep. Objectively measured sleep times have not been often reported. This study describes sleep, sleepiness, fatigue, and neurobehavioral performance over three consecutive 12-h (day and night) shifts for hospital registered nurses. Sleep (actigraphy), sleepiness (Karolinska Sleepiness Scale [KSS]), and vigilance (Performance Vigilance Task [PVT]), were measured serially in 80 registered nurses (RNs). Occupational fatigue (Occupational Fatigue Exhaustion Recovery Scale [OFER]) was assessed at baseline. Sleep was short (mean 5.5 h) between shifts, with little difference between day shift (5.7 h) and night shift (5.4 h). Sleepiness scores were low overall (3 on a 1-9 scale, with higher score indicating greater sleepiness), with 45% of nurses having high level of sleepiness (score  > 7) on at least one shift. Nurses were progressively sleepier each shift, and night nurses were sleepier toward the end of the shift compared to the beginning. There was extensive caffeine use, presumably to preserve or improve alertness. Fatigue was high in one-third of nurses, with intershift fatigue (not feeling recovered from previous shift at the start of the next shift) being most prominent. There were no statistically significant differences in mean reaction time between day/night shift, consecutive work shift, and time into shift. Lapsing was traitlike, with rare (39% of sample), moderate (53%), and frequent (8%) lapsers. Nurses accrue a considerable sleep debt while working successive 12-h shifts with accompanying fatigue and sleepiness. Certain nurses appear more vulnerable to sleep loss than others, as measured by attention lapses.

  11. Daytime sleepiness and EEG abnormalities in patients treated with second generation antipsychotic agents.

    Science.gov (United States)

    Okruszek, Lukasz; Jernajczyk, Wojciech; Wierzbicka, Aleksandra; Waliniowska, Elżbieta; Jakubczyk, Tomasz; Jarema, Marek; Wichniak, Adam

    2014-12-01

    The aim of this study was to verify whether or not an increased prevalence of excessive daytime sleepiness (EDS) or EEG abnormalities is observed in patients with schizophrenia spectrum disorders (SSD), and to compare the effects of second generation antipsychotics (SGA) on patients' daytime sleepiness level and EEG recordings. EEG recordings and self-reports of EDS, assessed with Epworth (ESS) and Stanford (SSS) Sleepiness Scales, were compared between 244 patients with SSD and 82 patients with anxiety, personality or behavioral disorders (non-psychotic disorders, NPD). To examine the effects of various SGA, patients treated in monotherapy with aripiprazole, olanzapine, clozapine, risperidone and sertindole were compared. A higher prevalence of abnormal EEG recordings was observed in SSD patients. No significant differences in average daytime sleepiness were found between patients with SSD and NPD; however, patients with SSD had longer sleep duration. Aripiprazole treatment was associated with significantly smaller and less frequent EEG abnormalities than treatment with any other SGA, while treatment with clozapine and olanzapine was related to an increased prevalence of severe EEG abnormalities. Patients with SSD treated with SGA in monotherapy were less sleepy than unmedicated patients with NPD. Although antipsychotics may have profound effects on EEG patients with schizophrenia do not have higher daytime sleepiness than patients with anxiety/personality disorders. Patients with schizophrenia may compensate sedative effects of antipsychotic treatment with sleep duration prolongation and report even less sleepiness than non-psychotic patients. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  12. Subjective Sleepiness and Sleep Quality in Adolescents are Related to Objective and Subjective Measures of School Performance

    OpenAIRE

    Boschloo, Annemarie; Krabbendam, Lydia; Dekker, Sanne; Lee, Nikki; de Groot, Renate; Jolles, Jelle

    2013-01-01

    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 grades, self-reported school performance, and parent-reported school performance. Sleepiness – “I feel sleepy during the first hours at school” – appeared to predict both school grades and self-re...

  13. Subjective sleepiness and sleep quality in adolescents are related to objective and subjective measures of school performance

    OpenAIRE

    Annemarie eBoschloo; Lydia eKrabbendam; Sanne eDekker; Nikki C Lee; Renate ede Groot; Renate ede Groot; Renate ede Groot; Jelle eJolles

    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 grades, self-reported school performance, and parent-reported school performance. Sleepiness – ‘I feel sleepy during the first hours at school’ – appeared to predict both school grades and self-repor...

  14. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. High Content Analysis of Human Pluripotent Stem Cell Derived Hepatocytes Reveals Drug Induced Steatosis and Phospholipidosis

    Directory of Open Access Journals (Sweden)

    Arvind Pradip

    2016-01-01

    Full Text Available Hepatotoxicity is one of the most cited reasons for withdrawal of approved drugs from the market. The use of nonclinically relevant in vitro and in vivo testing systems contributes to the high attrition rates. Recent advances in differentiating human induced pluripotent stem cells (hiPSCs into pure cultures of hepatocyte-like cells expressing functional drug metabolizing enzymes open up possibilities for novel, more relevant human cell based toxicity models. The present study aimed to investigate the use of hiPSC derived hepatocytes for conducting mechanistic toxicity testing by image based high content analysis (HCA. The hiPSC derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis, measuring several endpoints representing different mechanisms involved in drug induced hepatotoxicity. The hiPSC derived hepatocytes were benchmarked to the HepG2 cell line and generated robust HCA data with low imprecision between plates and batches. The different parameters measured were detected at subcytotoxic concentrations and the order of which the compounds were categorized (as severe, moderate, mild, or nontoxic based on the degree of injury at isomolar concentration corresponded to previously published data. Taken together, the present study shows how hiPSC derived hepatocytes can be used as a platform for screening drug induced hepatotoxicity by HCA.

  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. Glucuronidation of drugs and drug-induced toxicity in humanized UDP-glucuronosyltransferase 1 mice.

    Science.gov (United States)

    Kutsuno, Yuki; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2014-07-01

    UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that catalyze glucuronidation of various drugs. Although experimental rodents are used in preclinical studies to predict glucuronidation and toxicity of drugs in humans, species differences in glucuronidation and drug-induced toxicity have been reported. Humanized UGT1 mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice) were recently developed. In this study, acyl-glucuronidations of etodolac, diclofenac, and ibuprofen in liver microsomes of hUGT1 mice were examined and compared with those of humans and regular mice. The kinetics of etodolac, diclofenac, and ibuprofen acyl-glucuronidation in hUGT1 mice were almost comparable to those in humans, rather than in mice. We further investigated the hepatotoxicity of ibuprofen in hUGT1 mice and regular mice by measuring serum alanine amino transferase (ALT) levels. Because ALT levels were increased at 6 hours after dosing in hUGT1 mice and at 24 hours after dosing in regular mice, the onset pattern of ibuprofen-induced liver toxicity in hUGT1 mice was different from that in regular mice. These data suggest that hUGT1 mice can be valuable tools for understanding glucuronidations of drugs and drug-induced toxicity in humans. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

    Science.gov (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

    2013-01-01

    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  19. 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.

  20. [DRUG-INDUCED LUPUS CAUSED BY LONG TERM MINOCYCLINE TREATMENT FOR ACNE VULGARIS].

    Science.gov (United States)

    Hanai, Shunichiro; Sato, Takeo; Takeda, Koichi; Nagatani, Katsuya; Iwamoto, Masahiro; Minota, Seiji

    2015-09-01

    An 18-year-old Japanese girl had received oral minocycline 200mg daily for treatment of acne vulgaris since 16 years old. She had a fever three months before admission, followed by joint pains in her knees, elbows and several proximal interphalangeal joints one month before admission. She was referred to our hospital because of a high serum level of anti-DNA antibody. She had already discontinued oral minocycline five weeks before admission, because she missed her medication refilled. On admission, the arthralgia and fever spontaneously resolved, and there were no laboratory evidence of hypocomplementemia and cytopenia. She had neither erythema nor internal organ involvements. Because her symptoms subsided spontaneously after the cessation of minocycline, she was considered to have drug-induced lupus. Both the arthralgia and fever did not relapse, and anti-ds DNA antibody returned to normal during a follow-up period without treatment. There are few reports of drug-induced lupus caused by minocycline in Japan. This case highlights the importance of considering minocycline-induced lupus.

  1. Role of Serotoninergic Pathways in Drug-induced Valvular Heart Disease and Diagnostic Features by Echocardiography

    Science.gov (United States)

    Smith, Sakima A.; Waggoner, Alan D.; de las Fuentes, Lisa; Davila-Roman, Victor G.

    2013-01-01

    Serotonin plays a significant role in the development of carcinoid heart disease, which primarily leads to fibrosis and contraction of right-sided heart valves. Recently, strong evidence has emerged that the use of specific drug classes such as ergot alkaloids (for migraine headaches), 5-hydroxytryptamine (5-HT or serotonin) uptake regulators/inhibitors (for weight reduction), and ergot-derived dopamine agonists (for Parkinson’s disease) can result in left-sided heart valve damage that resembles carcinoid heart disease. Recent studies suggest that both right- and left-sided drug-induced heart valve disease involves increased serotoninergic activity and in particular activation of the 5-HT receptors, including the 5-HT2B receptor subtype, which mediate many of the central and peripheral functions of serotonin. G-proteins that inhibit adenylate cyclase activity mediate the activity of the 5-HT2B receptor subunit which is widely expressed in a variety of tissues including liver, lung, heart, and coronary and pulmonary arteries; and it has also been reported in embryonic mouse heart, particularly on mouse heart valve leaflets. In this review we discuss the salient features of serotoninergic manifestations of both carcinoid heart disease and drug-induced cardiac valvulopathy with an emphasis on echocardiographic diagnosis. PMID:19553085

  2. 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.

  3. Nintendo® Wii Fit based sleepiness tester detects impairment of postural steadiness due to 24 h of wakefulness.

    Science.gov (United States)

    Tietäväinen, Aino; Gates, Fred K; Meriläinen, Antti; Mandel, Jeff E; Hæggström, Edward

    2013-12-01

    A field-usable sleepiness tester could reduce sleepiness related accidents. 15 subjects' postural steadiness was measured with a Nintendo(®) Wii Fit balance board every hour for 24 h. Body sway was quantified with complexity index, CI, and the correlation between CI and alertness predicted by a three-process model of sleepiness was calculated. The CI group average was 8.9 ± 1.3 for alert and 7.9 ± 1.4 for sleep deprived subjects (p Wii Fit board detects the impairment of postural steadiness. This may allow large scale sleepiness testing outside the laboratory setting. Copyright © 2013 IPEM. All rights reserved.

  4. The relation between shift work, sleepiness, fatigue and accidents in Iranian Industrial Mining Group workers.

    Science.gov (United States)

    Halvani, Gholam Hossein; Zare, Mohsen; Mirmohammadi, Seyed Jalil

    2009-04-01

    The aim of this study was to examine the rate of fatigue and sleepiness around the shift and non-shift workers and its relation to occupational accidents. This was a cross-sectional study on the workers of Iranian Industrial Mining Group. They included 137 shift workers as the case and 130 non-shift workers as the control. A multi-part questionnaire including demographic characteristics, Piper Fatigue Scale and Epworth Sleepiness Scale were applied. The chi(2) test and t-test were used to measure differences between variables. The mean of PFS scores in the two groups was significantly different (p=0.045), but the difference in the mean of ESS scores was not significant. Shift workers with the reported accident had a higher score on fatigue than shift workers with no accident (paccidents in the two groups was not related significantly to the rate of sleepiness. The rate of fatigue and the number of the work accidents was more in the shift workers. Also, fatigue had a stronger relationship with the occupational accidents as compared to sleepiness. It seems that evaluation of fatigue as compared to sleepiness is a more accurate factor for preventing work accidents.

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

    Science.gov (United States)

    Di Milia, Lee; Rogers, Naomi L; Åkerstedt, Torbjörn

    2012-01-01

    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, psleep in the previous 48 hours (OR = 2.58, CI, 1.03-6.46, pmobile phones during the journey (OR = 1.90, CI, 1.10-3.27, pSleep 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.

  6. Caffeine or melatonin effects on sleep and sleepiness after rapid eastward transmeridian travel.

    Science.gov (United States)

    Beaumont, M; Batéjat, D; Piérard, C; Van Beers, P; Denis, J B; Coste, O; Doireau, P; Chauffard, F; French, J; Lagarde, D

    2004-01-01

    We measured the effects of slow-release caffeine (SRC) and melatonin (Mlt) on sleep and daytime sleepiness after a seven-time zone eastbound flight. In a double-blind, randomized, placebo-controlled study, each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 (D1) to D5 (0800) or 5 mg Mlt on preflight D-1 (1700), flight day D0 (1600), and from D1 to D3 (2300), or placebo (Pbo) at the same times. Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy. Compared with baseline, we found a significant rebound of slow-wave sleep on night 1 (N1) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 (Pbo) and N1-N3 (Mlt). Sleepiness was objectively increased under Pbo (D1-D6) and Mlt (D1-D3). SRC reduced sleepiness but also tended to affect sleep quality until the last drug day. In conclusion, both drugs have positive effects on some jet lag symptoms after an eastbound flight: SRC on daytime sleepiness, and Mlt on sleep.

  7. 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.

  8. 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.

  9. Effect of chronic sleep restriction on sleepiness and working memory in adolescents and young adults.

    Science.gov (United States)

    Jiang, Fan; VanDyke, Rhonda D; Zhang, Jiange; Li, Feng; Gozal, David; Shen, Xiaoming

    2011-10-01

    To test the feasibility of using a home-based sleep restriction protocol in adolescents and young adults; and to examine the different effects of chronic sleep restriction on a subjective sleepiness scale and working memory task in adolescents and young adults. Twenty adolescents (ages 13-16 years) and 20 young adults (ages 18-20 years) underwent a 2-week home-based sleep manipulation protocol consisting of a week of 5 school days with 8 hr spent in bed per night and another week of 5 school days with 6 hr spent in bed per night. The protocol used a counterbalanced crossover experimental design. Subjective sleepiness was scored by the participant each morning, and working memory tests were administered during the weekend corresponding to each experimental week. Adherence to the prescribed protocol was similar in the two groups, and both groups achieved the desired differences in total sleep duration across the two sleep conditions. Subjective sleepiness scores significantly increased in young adults after sleep restriction, but were not accompanied by significant changes in working memory. However, reaction times during simple verbal and arithmetic working memory tasks increased among adolescents after sleep restriction, without affecting accuracy on task, and without eliciting increases in subjective sleepiness scores. Mild sleep restriction for 5 days impairs reaction times during working memory tasks in adolescents in the absence of increased perception of sleepiness.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Levothyroxine improves subjective sleepiness in a euthyroid patient with narcolepsy without cataplexy.

    Science.gov (United States)

    Sobol, Danielle L; Spector, Andrew R

    2014-11-15

    We discuss the use of levothyroxine for excessive daytime sleepiness (EDS) and prolonged nocturnal sleep time in a euthyroid patient with narcolepsy. 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). 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. Levothyroxine improved EDS and total sleep time in a euthyroid patient with narcolepsy without cataplexy after 12 weeks without side effects. © 2014 American Academy of Sleep Medicine.

  15. The role of drug-induced sleep endoscopy in the diagnosis and management of obstructive sleep apnoea syndrome: our personal experience.

    Science.gov (United States)

    DE Corso, E; Fiorita, A; Rizzotto, G; Mennuni, G F; Meucci, D; Giuliani, M; Marchese, M R; Levantesi, L; Della Marca, G; Paludetti, G; Scarano, E

    2013-12-01

    Nowadays, drug-induced sleep endoscopy (DISE) is performed widely and its validity and reliability has been demonstrated by several studies; in fact, it provides clinical information not available by routine clinical inspection alone. Its safety and utility are promising, but still needs to be improved to reach the level of excellence expected of gold standard tests used in clinical practice. Our study compares the results of clinical and diagnostic evaluation with those of sleep endoscopy, evaluating the correlation between clinical indexes of routine clinical diagnosis and sites of obstruction in terms of number of sites involved, entity of obstruction and pattern of closure. This study consists in a longitudinal prospective evaluation of 138 patients who successfully underwent sleep endoscopy at our institution. Patients were induced to sleep with a low dose of midazolam followed by titration with propofol. Sedation level was monitored using bispectral index monitoring. Our results suggest that the multilevel complete collapse was statistically significantly associated with higher apnoea hypopnea index values. By including partial sites of obstruction greater than 50%, our results also suggest that multilevel collapse remains statistically and significantly associated with higher apnoea hypopnoea index values. Analyzing BMI distribution based on number of sites with complete and partial obstruction there was no significant difference. Finally, analyzing Epworth Sleepiness Score distribution based on number of sites with complete obstruction, there was a statistically significant difference between patients with 3-4 sites of obstruction compared to those with two sites or uni-level obstruction. In conclusion, our data suggest that DISE is safe, easy to perform, valid and reliable, as previously reported. Furthermore, we found a good correlation between DISE findings and clinical characteristics such as AHI and EPS. Consequently, adequate assessment by DISE of all

  16. 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.

  17. 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.

  18. Alpha attenuation soon after closing the eyes as an objective indicator of sleepiness.

    Science.gov (United States)

    Putilov, Arcady A; Donskaya, Olga G

    2014-12-01

    Attenuation of alpha rhythm in occipital derivation serves as a reliable electroencephalographic (EEG) marker of sleep onset. If such attenuation not only coincides with but also anticipates sleep onset, objective evaluation of sleepiness of permanently waking individuals might be facilitated by probing alpha attenuation immediately after closing eyes. We tested whether alpha-based EEG indexes reflect self-scored sleepiness and objectively measured waking ability. A total of 15 young adults self-scored their sleepiness before and after recording of their resting EEG with a 2-h interval in the course of 43-61-h wakefulness. For each EEG record, power spectra were calculated on 2-min intervals of the eyes open section and on five following 1-min intervals of the eyes closed section. Aking ability was assessed as latency to sleep onset marked by zero-crossing decline of such EEG indexes as alpha-theta power difference in occipital derivation and scores on the second principal component of the EEG spectrum in frontal and occipital derivations. Alpha attenuation during the first minute with eyes closed was found to be significantly related to the levels of subjective sleepiness and waking ability. The relationship between alpha attenuation and subjective sleepiness was confirmed by analysing 1-min eyes closed EEG recordings obtained with a 3-h interval in the course of 24-h sustained wakefulness of 130 adolescents and adults. We concluded that such 1-min eyes closed EEG recordings might be used for simple and quick measurements of sleepiness and waking ability in experimental and field studies of permanently waking individuals. © 2014 Wiley Publishing Asia Pty Ltd.

  19. 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.

  20. 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.

  1. Comparing sleep-loss sleepiness and sleep inertia: lapses make the difference.

    Science.gov (United States)

    Miccoli, Laura; Versace, Francesco; Koterle, Sara; Cavallero, Corrado

    2008-09-01

    To compare the behavioral effects of sleep-loss sleepiness (performance impairment due to sleep loss) and sleep inertia (period of impaired performance that follows awakening), mean response latencies and number of lapses from a visual simple reaction-time task were analyzed. Three experimental conditions were designed to manipulate sleepiness and sleep-inertia levels: uninterrupted sleep, partial sleep reduction, and total sleep deprivation. Each condition included two consecutive nights (the first always a night of uninterrupted sleep, and the second either a night of uninterrupted sleep, a night when sleep was reduced to 3 h, or a night of total sleep deprivation), as well as two days in which performance was assessed at 10 different time points (08:00, 08:30, 09:00, 09:30, 10:00, 11:00, 14:00, 17:00, 20:00, and 23:00 h). From 08:00 to 09:00 h, reaction times in the partial sleep-reduction and total sleep-deprivation conditions were at a similar level and were slower than those observed in the uninterrupted sleep condition. In the same time period, the frequency of lapses in the total sleep-deprivation condition was higher than in the partial sleep-reduction condition, while this latter condition never differed from the uninterrupted sleep condition. The results indicate that both sleep inertia and sleep-loss sleepiness lead to an increase in response latencies, but only extreme sleepiness leads to an increase in lapse frequency. We conclude that while reaction times slow as a result of both sleep inertia and sleep-loss sleepiness, lapses appear to be a specific feature of sleep-loss sleepiness.

  2. Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Khat Use among College Students in Ethiopia.

    Science.gov (United States)

    Robinson, Darve; Gelaye, Bizu; Tadesse, Mahlet G; Williams, Michelle A; Lemma, Seblewengel; Berhane, Yemane

    2013-12-20

    To estimate the prevalence of daytime sleepiness and circadian preferences, and to examine the extent to which caffeine consumption and Khat (a herbal stimulant) use are associated with daytime sleepiness and evening chronotype among Ethiopian college students. A cross-sectional study was conducted among 2,410 college students. A self-administered questionnaire was used to collect information about sleep, behavioral risk factors such as caffeinated beverages, tobacco, alcohol, and Khat consumption. Daytime sleepiness and chronotype were assessed using the Epworth Sleepiness Scale (ESS) and the Horne & Ostberg Morningness /Eveningness Questionnaire (MEQ), respectively. Linear and logistic regression models were used to evaluate associations. Daytime sleepiness (ESS≥10) was present in 26% of the students (95% CI: 24.4-27.8%) with 25.9% in males and 25.5% in females. A total of 30 (0.8%) students were classified as evening chronotypes (0.7% in females and 0.9% in males). Overall, Overall, Khat consumption, excessive alcohol use and cigarette smoking status were associated with evening chronotype. Use of any caffeinated beverages (OR=2.18; 95%CI: 0.82-5.77) and Khat consumption (OR=7.43; 95%CI: 3.28-16.98) increased the odds of evening chronotype. The prevalence of daytime sleepiness among our study population was high while few were classified as evening chronotypes. We also found increased odds of evening chronotype with caffeine consumption and Khat use amongst Ethiopian college students. Prospective cohort studies that examine the effects of caffeinated beverages and Khat use on sleep disorders among young adults are needed.

  3. Dynamically observing the value of the changes of serum sex hormone levels of early pregnancy after drug-induced abortion

    International Nuclear Information System (INIS)

    Zhao Honggang; Dong Hua; Gu Yan; Zhang Zuncheng

    2009-01-01

    Objective: To observe the value of the changes of serum β-human chorionic gonadotropin (β-HCG), estradiol (E), progesterone (P) Levels of early pregnancy after drug-induced abortion dynamically. Methods: Assessing 55 women proved pregnant by urine or blood HCG retrospecticly, who had terminated their pregnancy by mifepristonr and misoprostol. Meanwhile the serum levels of β-HCG, E, P were monitored dynamically. Results: Among the 55 patients, the levels of β-HCG, E and P had significant decreased (t β-HCG =4.845, t E =7.655, t P =11.390, P E =9.089, P P =2.910, P<0.05). Conclusion: Detectint the serum hormone's levels after drug-induced abortion by chemiluminescent immunoassay, we can assess indirectly the value of administration of mifepristone and misoprostol, predict the prolonged vaginal bleeding after drug-induced abortion, and the outcome of the treatment, which determine wether need another curestage. (authors)

  4. Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity.

    Science.gov (United States)

    Samuel, Anbu Jeba Sunilson John; Mohan, Syam; Chellappan, Dinesh Kumar; Kalusalingam, Anandarajagopal; Ariamuthu, Saraswathi

    2012-05-07

    The roots of Hibiscus vitifolius Linn. (Malvaceae) is used for the treatment of jaundice in the folklore system of medicine in India. This study is an attempt to evaluate the hepatoprotective activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced hepatotoxicity. Hepatotoxicity was induced in albino rats of either sex by oral administration of a combination of three anti-tubercular drugs. Petroleum ether, chloroform, methanol and aqueous extracts of roots of Hibiscus vitifolius (400mg/kg/day) were evaluated for their possible hepatoprotective potential. All the extracts were found to be safe up to a dose of 2000mg/kg. Among the four extracts studied, oral administration of methanol extract of Hibiscus vitifolius at 400mg/kg showed significant difference in all the parameters when compared to control. There was a significant (PHibiscus vitifolius have potent hepatoprotective activity, thereby justifying its ethnopharmacological claim. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Okadaic acid for radiation dose estimation using drug-induced premature chromosome condensation

    International Nuclear Information System (INIS)

    Wang Chunyan; Zhang Wei; Su Xu

    2005-01-01

    Objective: To establish simple biological method for high irradiation dose estimation using drug-induced prematurely condensed chromosomes (PCC) aberrations. Methods: Peripheral blood was taken from healthy adults and irradiated by 0, 1, 2, 5, 10, 15, 20 and 25 Gy 60 Co γ-rays. Then the blood samples were cultured for 48 hrs. One hr before the end of culture , okadaic acid was added into culture medium to induce PCC rings, which were counted for each dose point. Results: The yield of PCC rings was increased with the dose of radiation until 20 Gy. Within the range of 1 to 20 Gy, there was a good dose-response relationship between the yield of PCC rings and radiation dose. Conclusion: Compared with the analysis of frequency of dicentrics, the yield of PCC rings could be a good biodosimetry indicator for estimation of high dose irradiation. (authors)

  6. Radiation- and drug-induced DNA repair in mammalian oocytes and embryos

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, R A; Brandriff, B

    1979-01-01

    A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte's demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintans a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair. These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos.

  7. Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report.

    Science.gov (United States)

    Laes, JoAn R; Williams, David M; Cole, Jon B

    2015-12-01

    The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient. This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg. Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.

  8. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

    Directory of Open Access Journals (Sweden)

    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.

  9. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death

    DEFF Research Database (Denmark)

    De Bruin, M L; Pettersson, M; Meyboom, R H B

    2005-01-01

    AND RESULTS: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were......AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS...... defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value...

  10. The drug-induced degradation of oncoproteins: an unexpected Achilles' heel of cancer cells?

    Science.gov (United States)

    Ablain, Julien; Nasr, Rihab; Bazarbachi, Ali; de Thé, Hugues

    2011-07-01

    Many targeted therapies against cancer are aimed at inhibiting the enzymatic activity of kinases. Thus far, this approach has undoubtedly yielded significant clinical improvements, but has only rarely achieved cures. Other drugs, which selectively elicit proteasome-dependent degradation of oncoproteins, induce the loss of cancer cell self-renewal and promote cell differentiation and/or apoptosis. In acute promyelocytic leukemia, the cooperative degradation of PML/RARA by arsenic and retinoic acid cures most patients. In this condition and others, drug-induced proteolysis of oncoproteins is feasible and underlies improved clinical outcome. Several transcription factors, nuclear receptors, or fusion proteins driving cancer growth could be candidates for proteolysis-based drug-discovery programs.

  11. Radiation- and drug-induced DNA repair in mammalian oocytes and embryos

    International Nuclear Information System (INIS)

    Pedersen, R.A.; Brandriff, B.

    1979-01-01

    A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte's demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintans a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair. These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos

  12. Bilateral macular hemorrhage as a complication of drug-induced anemia: a case report

    Directory of Open Access Journals (Sweden)

    Belfort Rubens N

    2009-01-01

    Full Text Available Abstract Introduction Bilateral macular hemorrhage is a rare ocular finding and to the best of our knowledge, this is the first report of such hemorrhages as a presentation of drug-induced anemia. Case presentation We describe the case of a 14-year-old Caucasian boy who presented with a toxoplasmic retinochoroiditis and was treated with sulfadiazine and pyrimethamine. Three months later, he presented with a bilateral macular hemorrhage as a complication of a toxic induced anemia. Conclusion Our patient presented with toxic anemia secondary to the treatment of a very common disease, ocular toxoplasmosis. Prophylactic use of folinic acid could prevent such complications but in many cases, it is not prescribed owing to its cost or is mistakenly substituted with folic acid, which does not present as a valid substitute.

  13. 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)

  14. Idiosyncratic Drug-Induced Liver Injury (IDILI: Potential Mechanisms and Predictive Assays

    Directory of Open Access Journals (Sweden)

    Alexander D. Roth

    2017-01-01

    Full Text Available Idiosyncratic drug-induced liver injury (IDILI is a significant source of drug recall and acute liver failure (ALF in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME- mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA. We then describe the various assays that have been developed to detect individual reactions focusing on each of the mechanisms described in the background. Finally, we examine current trends in developing comprehensive models for examining these mechanisms. There is an urgent need to develop a panel of multiparametric assays for diagnosing individual toxicity potential.

  15. Lack of correlation between fecal blood loss and drug-induced gastric mucosal lesions

    International Nuclear Information System (INIS)

    Hedenbro, J.L.; Wetterberg, P.; Vallgren, S.; Bergqvist, L.

    1988-01-01

    Increased fecal blood loss was produced in healthy volunteers by the administration of two nonsteroidal anti-inflammatory drugs (NSAID), naproxen or fenflumizole. Basal as well as drug-induced gastrointestinal blood loss was measured using 51 Cr erythrocyte labeling. Median rise in daily fecal blood loss was 432%. All subjects were endoscoped at the initiation and at the completion of the study. Endoscopic findings were assessed quantitatively by two observers in two different ways. All subjects but three had gastric mucosal lesions at follow-up endoscopy. There was a good correlation between the endoscopic assessments but no statistical correlation between the endoscopic assessment and the increase in fecal blood loss. The data suggest that factors other than gastric mucosal lesions have to be taken into account when investigating NSAID-induced gastrointestinal bleeding

  16. Acoustic analysis of snoring sounds originating from different sources determined by drug-induced sleep endoscopy.

    Science.gov (United States)

    Peng, Hao; Xu, Huijie; Xu, Zhiyong; Huang, Weining; Jia, Ruifang; Yu, Hui; Zhao, Zhao; Wang, Jiajun; Gao, Zhan; Zhang, Qiuying; Huang, Weihong

    2017-08-01

    To discuss the possibility of fundamental frequency (F0) and formant frequency (FF) to generally differentiate the sources of snoring sounds determined by drug-induced sleep endoscopy (DISE). A total of 74 snoring subjects underwent DISE and snoring sounds were recorded simultaneously. The noise-suppressed snoring sounds were analyzed and classified into different groups based on the sources of vibration identified by DISE. F0 and FFs were calculated. Totally, 516 snoring sounds from three vibrating sources (the palate, combined the palate and the lateral wall, the lateral wall) of 47 patients were divided into three groups then analyzed. The levels of F0 and FFs for each group follow the order: Group 1 snoring sound. F0 might be a significant in distinguishing palatal snoring sound from non-palatal snoring sound. F2 is more significant than F1 and F3 in identifying the sources of the snoring sounds but is less sensitive than F0.

  17. Breathing Disturbances Without Hypoxia Are Associated With Objective Sleepiness in Sleep Apnea.

    Science.gov (United States)

    Koch, Henriette; Schneider, Logan Douglas; Finn, Laurel A; Leary, Eileen B; Peppard, Paul E; Hagen, Erika; Sorensen, Helge Bjarup Dissing; Jennum, Poul; Mignot, Emmanuel

    2017-11-01

    To determine whether defining two subtypes of sleep-disordered breathing (SDB) events-with or without hypoxia-results in measures that are more strongly associated with hypertension and sleepiness. A total of 1022 participants with 2112 nocturnal polysomnograms from the Wisconsin Sleep Cohort were analyzed with our automated algorithm, developed to detect breathing disturbances and desaturations. Breathing events were time-locked to desaturations, resulting in two indices-desaturating (hypoxia-breathing disturbance index [H-BDI]) and nondesaturating (nonhypoxia-breathing disturbance index [NH-BDI]) events-regardless of arousals. Measures of subjective (Epworth Sleepiness Scale) and objective (2981 multiple sleep latency tests from a subset of 865 participants) 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 ≤ .001 with 3% oxygen-desaturation index [ODI] and apnea hypopnea index 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 < .05; H-BDI OR 1.04, 95% CI = 0.98-1.10) and daytime sleepiness (β = 0.20 Epworth Sleepiness Scale [ESS] score, p < .0001; β = -0.20 minutes in MSL on multiple sleep latency test [MSLT], p < .01). Independently, nondesaturating event doubling was associated with more objective sleepiness (β = -0.52 minutes in MSL on MSLT, p < .001), but had less association with subjective sleepiness (β = 0.12 ESS score, p = .10). In longitudinal analyses, baseline nondesaturating events were associated with worsening of H-BDI over a 4-year follow-up, suggesting evolution in severity. In SDB, nondesaturating events are independently associated with objective daytime sleepiness, beyond the

  18. 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.

  19. 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...

  20. A Patient with Nafcillin-Associated Drug-Induced Liver Failure.

    Science.gov (United States)

    Rao, Qin; Schuster, Isaiah; Seoud, Talal; Zarrabi, Kevin; Goolsarran, Nirvani

    2017-01-01

    Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient's lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient's liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

  1. A Patient with Nafcillin-Associated Drug-Induced Liver Failure

    Directory of Open Access Journals (Sweden)

    Qin Rao

    2017-09-01

    Full Text Available Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

  2. 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.

  3. Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury.

    Science.gov (United States)

    Medina-Caliz, Inmaculada; Robles-Diaz, Mercedes; Garcia-Muñoz, Beatriz; Stephens, Camilla; Ortega-Alonso, Aida; Garcia-Cortes, Miren; González-Jimenez, Andres; Sanabria-Cabrera, Judith A; Moreno, Inmaculada; Fernandez, M Carmen; Romero-Gomez, Manuel; Navarro, Jose M; Barriocanal, Ana M; Montane, Eva; Hallal, Hacibe; Blanco, Sonia; Soriano, German; Roman, Eva M; Gómez-Dominguez, Elena; Castiella, Agustin; Zapata, Eva M; Jimenez-Perez, Miguel; Moreno, Jose M; Aldea-Perona, Ana; Hernández-Guerra, Manuel; Prieto, Martin; Zoubek, Miguel E; Kaplowitz, Neil; Lucena, M Isabel; Andrade, Raul J

    2016-09-01

    Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (prisk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Update on Advances in Research on Idiosyncratic Drug-Induced Liver Injury.

    Science.gov (United States)

    Kim, Seung Hyun; Naisbitt, Dean J

    2016-01-01

    Drug-induced liver injury (DILI) is a major concern for public health, as well as for drug development in the pharmaceutical industry, since it can cause liver failure and lead to drug withdrawal from the market and black box warnings. Thus, it is important to identify biomarkers for early prediction to increase our understanding of mechanisms underlying DILI that will ultimately aid in the exploration of novel therapeutic strategies to prevent or manage DILI. DILI can be subdivided into 'intrinsic' and 'idiosyncratic' categories, although the validity of this classification remains controversial. Idiosyncratic DILI occurs in a minority of susceptible individuals with a prolonged latency, while intrinsic DILI results from drug-induced direct hepatotoxicity over the course of a few days. The rare occurrence of idiosyncratic DILI requires multicenter collaborative investigations and phenotype standardization. Recent progress in research on idiosyncratic DILI is based on key developments in 3 areas: (1) newly developed high-throughput genotyping across the whole genome allowing for the identification of genetic susceptibility markers, (2) new mechanistic concepts on the pathogenesis of DILI revealing a key role of drug-responsive T lymphocytes in the immunological response, and (3) broad multidisciplinary approaches using different platform "-omics" technologies that have identified novel biomarkers for the prediction of DILI. An association of a specific human leukocyte antigen (HLA) allele with DILI has been reported for several drugs. HLA-restricted T-cell immune responses have also been investigated using lymphocytes and T-cell clones isolated from patients. A microRNA, miR-122, has been discovered as a promising biomarker for the early prediction of DILI. In this review, we summarize recent advances in research on idiosyncratic DILI with an understanding of the key role of adaptive immune systems.

  5. Sleep-Wake Cycle, Daytime Sleepiness, and Attention Components in Children Attending Preschool in the Morning and Afternoon Shifts

    Science.gov (United States)

    Belísio, Aline S.; Kolodiuk, Fernanda F.; Louzada, Fernando M.; Valdez, Pablo; Azevedo, Carolina V. M.

    2017-01-01

    Children tend to sleep and wake up early and to exhibit daytime sleep episodes. To evaluate the impact of school start times on sleepiness and attention in preschool children, this study compared the temporal patterns of sleep, daytime sleepiness, and the components of attention between children aged 4-6 years that study in the morning (n = 66)…

  6. The Epworth Sleepiness Scale: Self-Administration Versus Administration by the Physician, and Validation of a French Version

    Directory of Open Access Journals (Sweden)

    Marta Kaminska

    2010-01-01

    Full Text Available BACKGROUND/OBJECTIVES: The Epworth Sleepiness Scale (ESS measures sleepiness and is used for, among others, patients with obstructive sleep apnea (OSA. The questionnaire is usually self-administered, but may be physician administered. The aim was to compare the two methods of administration and to validate a French version.

  7. Factors associated with self-reported driver sleepiness and incidents in city bus drivers

    NARCIS (Netherlands)

    Anund, A.; Ihlström, J.; Fors, C.; Kecklund, L.G.; Filtness, A.J.

    2016-01-01

    Driver fatigue has received increased attention during recent years and is now considered to be a major contributor to approximately 15-30% of all crashes. However, little is known about fatigue in city bus drivers. It is hypothesized that city bus drivers suffer from sleepiness, which is due to a

  8. Self-Regulation and Sleep Duration, Sleepiness, and Chronotype in Adolescents.

    Science.gov (United States)

    Owens, Judith A; Dearth-Wesley, Tracy; Lewin, Daniel; Gioia, Gerard; Whitaker, Robert C

    2016-12-01

    To determine whether shorter school-night sleep duration, greater daytime sleepiness, and greater eveningness chronotype were associated with lower self-regulation among adolescents. An online survey of 7th- to 12th-grade students in 19 schools in Fairfax County, Virginia Public Schools was conducted in 2015. Self-regulation was measured with the Behavior Rating Inventory of Executive Function, 2nd edition, Screening Self-Report Form. Sleep measures included school night-sleep duration (hours between usual bedtime and wake time), daytime sleepiness (Sleepiness Scale in the Sleep Habits Survey, tertiles), and chronotype (Morningness-Eveningness Scale for Children, continuous score and tertiles). Sociodemographic factors and mental health conditions were analyzed as potential confounders. Among 2017 students surveyed, the mean age was 15.0 years (range, 12.1-18.9 years), and 21.7% slept self-regulation and both chronotype (P self-regulation, as did those in the eveningness tertile of chronotype compared with those in the morningness tertile (0.35 SD units lower; 95% confidence interval, 0.24-0.46). Among adolescents, greater daytime sleepiness and greater eveningness chronotype were independently associated with lower self-regulation, but shorter sleep duration was not. Aspects of sleep other than school-night sleep duration appear to be more strongly associated with self-regulation. Copyright © 2016 by the American Academy of Pediatrics.

  9. Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects.

    Science.gov (United States)

    Richardson, G S; Carskadon, M A; Flagg, W; Van den Hoed, J; Dement, W C; Mitler, M M

    1978-11-01

    Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness--sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o'clock, +/- 30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.

  10. 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.

  11. 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,…

  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. 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. 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

  15. 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.

  16. 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...

  17. 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

  18. Common Variation in the NOS1AP Gene Is Associated With Drug-Induced QT Prolongation and Ventricular Arrhythmia

    NARCIS (Netherlands)

    Jamshidi, Yalda; Nolte, Ilja M.; Dalageorgou, Chrysoula; Zheng, Dongling; Johnson, Toby; Bastiaenen, Rachel; Ruddy, Suzanne; Talbott, Daniel; Norris, Kris J.; Snieder, Harold; George, Alfred L.; Marshall, Vanessa; Shakir, Saad; Kannankeril, Prince J.; Munroe, Patricia B.; Camm, A. John; Jeffery, Steve; Roden, Dan M.; Behr, Elijah R.

    2012-01-01

    Objectives This study sought to determine whether variations in NOS1AP affect drug-induced long QT syndrome (LQTS). Background Use of antiarrhythmic drugs is limited by the high incidence of serious adverse events including QT prolongation and torsades de pointes. NOS1AP gene variants play a role in

  19. 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

  20. Excessive Daytime Sleepiness is Associated with Increased Health Care Utilization Among Patients Referred for Assessment of OSA

    Science.gov (United States)

    Ronksley, Paul E.; Hemmelgarn, Brenda R.; Heitman, Steven J.; Flemons, W. Ward; Ghali, William A.; Manns, Braden; Faris, Peter; Tsai, Willis H.

    2011-01-01

    Study Objectives: Excessive daytime sleepiness is an important public health concern associated with increased morbidity and mortality. However, in the absence of sleep diagnostic testing, it is difficult to separate the independent effects of sleepiness from those of intrinsic sleep disorders such as obstructive sleep apnea (OSA). The objective of this study was to determine if excessive daytime sleepiness was independently associated with increased health care utilization among patients referred for assessment of OSA. Design: Cross-sectional study. Setting/Participants: 2149 adults referred for sleep diagnostic testing between July 2005 and August 2007. Interventions: N/A Measurements: Subjective daytime sleepiness was defined as an Epworth Sleepiness Scale score ≥10. Health care use (outpatient physician visits, all-cause hospitalizations, and emergency department visits) was determined from Alberta Health and Wellness administrative databases for the 18-month period preceding their sleep study. Rates of health resource use were analyzed using negative binomial regression, with predictors of increased health care use determined using logistic regression. Results: Excessive daytime sleepiness was associated with an increased rate of outpatient physician visits after adjustment for demographic variables, sleep medication use, hypertension, diabetes, depression, and OSA severity (rate ratio [RR]: 1.09 (95% confidence interval [CI]: 1.01, 1.18, P = 0.02) compared to non-sleepy subjects. There was an interaction between severe OSA and sleepiness (RR: 1.22 [95% CI: 1.06, 1.41]), although OSA was not an independent predictor of health care use. Also, sleepy patients with treated depression had a lower likelihood of outpatient visits (RR: 0.95 [95% CI: 0.86, 1.05]). Finally, sleepiness was an independent predictor of increased health care use for outpatient physician visits (odds ratio [OR]: 1.25 [95% CI: 1.00, 1.57; P = 0.048]) and all-cause hospitalizations (OR: 3

  1. 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.

  2. A comparison of three different sleep schedules for reducing daytime sleepiness in narcolepsy.

    Science.gov (United States)

    Rogers, A E; Aldrich, M S; Lin, X

    2001-06-15

    To determine if the combination of scheduled sleep periods and stimulant medications were more effective than stimulant medications alone in controlling the excessive daytime sleepiness experienced by narcoleptic patients. Twenty-nine treated narcoleptic subjects were randomly assigned to one of three treatment groups: 1) two 15-minute naps per day; 2) a regular schedule for nocturnal sleep; or 3) a combination of scheduled naps and regular bedtimes. Measures of symptom severity and unscheduled daytime were obtained at baseline and at the end of the two-week treatment period, using the Narcolepsy Symptom Status Questionnaire (NSSQ) and 24-hour ambulatory polysomnographic monitoring. No alterations were made in stimulant medications during the study period. N/A. N/A. N/A. The addition of two-15 minute naps did not alter either symptom severity or the duration of unscheduled daytime sleep. Regular times for nocturnal sleep reduced perceived symptom severity, but did not reduce the amount of unscheduled daytime sleep. Only the combination of scheduled naps and regular nocturnal sleep times, significantly reduced both symptom severity and the amount of unscheduled daytime sleep in treated narcoleptic subjects. The type of sleep schedule prescribed, however, was less important than the severity of the patients' pre-treatment daytime sleepiness. Subjects with severe daytime sleepiness benefited from the addition of scheduled sleep periods, while those who were only moderately sleepy or able to maintain alertness did not benefit from scheduled sleep periods. Scheduled sleep periods are helpful for only those patients who remain profoundly sleepy despite stimulant medications and should not be prescribed for all patients with narcolepsy.

  3. 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.

    2016-01-01

    Study Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Commentary: A commentary on this article appears in this issue on page 497. Citation: Lo JC, Ong JL, Leong RL, Gooley JJ, Chee MW. Cognitive performance, sleepiness, and mood in partially sleep deprived adolescents: the need for sleep study

  4. Lack of impact of mild obstructive sleep apnea on sleepiness, mood and quality of life

    Directory of Open Access Journals (Sweden)

    Quan SF

    2014-07-01

    Full Text Available Background and Objectives: Obstructive sleep apnea (OSA is associated with sleepiness, depression and reduced quality of life. However, it is unclear whether mild OSA has these negative impacts. Using data from the Apnea Positive Pressure Long-term Efficacy Study (APPLES, this study determined whether participants with mild OSA had greater sleepiness, more depressive symptoms and poorer quality of life in comparison to those without OSA. Methods: 239 evaluated for participation in APPLES with a baseline apnea hypopnea index (AHI < 15 /hour were assigned to 1 of 2 groups: No OSA (N=40, AHI < 5 /hour or Mild OSA (N=199, 5 to <15 /hour based on their screening polysomnogram. Scores on their Epworth Sleepiness Scale (ESS, Stanford Sleepiness Scale (SSS, Hamilton Rating Scale for Depression (HAM-D, Profile of Mood States (POMS and Sleep Apnea Quality of Life Index (SAQLI were compared between groups. Results: There were no significant differences between the No OSA and Mild OSA groups on any of the 5 measures: ESS (OSA, 9.8 + 3.5 vs Mild OSA, 10.6 + 4.3, p=0.26, SSS,(2.8 + 0.9 vs. 2.9 + 1.0, p=0.52, HAM-D (4.6 + 3.0 vs. 4.9 + 4.7, p=0.27, POMS (33.5 + 22.3 vs. 28.7 + 22.0, p=0.70, SAQLI (4.5 + 0.8 vs. 4.7 + 0.7, p=0.39. Conclusion: Individuals with mild OSA in this cohort do not have worse sleepiness, mood or quality of life in comparison to those without OSA.

  5. Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Use of Other Stimulants among Thai College Students.

    Science.gov (United States)

    Tran, Jason; Lertmaharit, Somrat; Lohsoonthorn, Vitool; Pensuksan, Wipawan C; Rattananupong, Thanapoom; Tadesse, Mahlet G; Gelaye, Bizu; Williams, Michelle A

    2014-06-01

    We conducted this study to evaluate the prevalence of daytime sleepiness and evening chronotype, and to assess the extent to which both are associated with the use of caffeinated stimulants among 3,000 Thai college students. Demographic and behavioral characteristics were collected using a self-administered questionnaire. The Epworth Sleepiness Scale and the Horne and Ostberg Morningness-Eveningness Questionnaire were used to evaluate prevalence of daytime sleepiness and circadian preference. Multivariable logistic regression models were used to evaluate the association between sleep disorders and consumption of caffeinated beverages. Overall, the prevalence of daytime sleepiness was 27.9 % (95% CI: 26.2-29.5%) while the prevalence of evening chronotype was 13% (95% CI: 11.8-14.2%). Students who use energy drinks were more likely to be evening types. For instance, the use of M100/M150 energy drinks was associated with a more than 3-fold increased odds of evening chronotype (OR 3.50; 95% CI 1.90-6.44), while Red Bull users were more than twice as likely to have evening chronotype (OR 2.39; 95% CI 1.02-5.58). Additionally, those who consumed any energy drinks were more likely to be daytime sleepers. For example, Red Bull (OR 1.72; 95% CI 1.08-2.75) or M100/M150 (OR 1.52; 95% CI 1.10-2.11) consumption was associated with increased odds of daytime sleepiness. Our findings emphasize the importance of implementing educational and prevention programs targeted toward improving sleep hygiene and reducing the consumption of energy drinks among young adults.

  6. An on-road study of sleepiness in split shifts among city bus drivers.

    Science.gov (United States)

    Anund, Anna; Fors, Carina; Ihlström, Jonas; Kecklund, Göran

    2017-05-12

    Bus drivers often work irregular hours or split shifts and their work involves high levels of stress. These factors can lead to severe sleepiness and dangerous driving. This study examined how split shift working affects sleepiness and performance during afternoon driving. An experiment was conducted on a real road with a specially equipped regular bus driven by professional bus drivers. The study had a within-subject design and involved 18 professional bus drivers (9 males and 9 females) who drove on two afternoons; one on a day in which they had driven early in the morning (split shift situation) and one on a day when they had been off duty until the test (afternoon shift situation). The hypothesis tested was that split shifts contribute to sleepiness during afternoon, which can increase the safety risks. The overall results supported this hypothesis. In total, five of the 18 drivers reached levels of severe sleepiness (Karolinska Sleepiness Scale ≥8) with an average increase in KSS of 1.94 when driving in the afternoon after working a morning shift compared with being off duty in the morning. This increase corresponded to differences observed between shift workers starting and ending a night shift. The Psychomotor Vigilance Task showed significantly increased response time with split shift working (afternoon: 0.337s; split shift 0.347s), as did the EEG-based Karolinska Drowsiness Score mean/max. Blink duration also increased, although the difference was not significant. One driver fell asleep during the drive. In addition, 12 of the 18 bus drivers reported that in their daily work they have to fight to stay awake while driving at least 2-4 times per month. While there were strong individual differences, the study clearly showed that shift-working bus drivers struggle to stay awake and thus countermeasures are needed in order to guarantee safe driving with split shift schedules. Copyright © 2017. Published by Elsevier Ltd.

  7. Circadian rhythm characteristics, poor sleep quality, daytime sleepiness and common psychiatric disorders among Thai college students.

    Science.gov (United States)

    Haregu, Alazar; Gelaye, Bizu; Pensuksan, Wipawan C; Lohsoonthorn, Vitool; Lertmaharit, Somrat; Rattananupong, Thanapoom; Tadesse, Mahlet G; Williams, Michelle A

    2015-06-01

    To investigate the relationship between common psychiatric disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep quality and daytime sleepiness) among Thai college students. A cross-sectional study was conducted among 2,970 undergraduate students in Thailand. Students were asked to complete a self-administered questionnaire that collected information about lifestyle and demographic characteristics. The Horne and Ostberg Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian preference, sleep quality and daytime sleepiness, respectively. The General Health Questionnaire-12 (GHQ-12) was used to evaluate presence of CPDs. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of CPDs in relation to the covariates of interest. A total of 337 students were classified as having CPDs (11.2%; 95% CI 10.1-12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09-5.37), poor sleep quality (OR = 4.89; 95% CI 3.66-6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI 1.54-2.47) were statistically significantly associated with CPDs. Our study demonstrated that CPDs are common among Thai college students. Further, evening chronotype, poor sleep quality and excessive daytime sleepiness were strongly associated with increased risk of CPDs. These findings highlight the importance of educating students and school administrators about the importance of sleep and their impact on mental health. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

  8. Operational definitions and algorithms for excessive sleepiness in the general population: implications for DSM-5 nosology.

    Science.gov (United States)

    Ohayon, Maurice M; Dauvilliers, Yves; Reynolds, Charles F

    2012-01-01

    Excessive sleepiness (ES) is poorly defined in epidemiologic studies, although its adverse implications for safety, health, and optimal social and vocational functioning have been extensively reported. To determine the importance of ES definition, measurement, and prevalence in the general population, together with its coexisting conditions. Cross-sectional telephone study. A total of 15 929 individuals representative of the adult general population of 15 states in the United States. Interviews were carried out using Sleep-EVAL, a knowledge-based expert system for use in epidemiologic studies, focusing on sleep, as well as physical and mental disorders, according to classification in DSM-IV and the second edition of the International Classification of Sleep Disorders. The interviews elicited information on ES, naps, frequency, duration, impairment, and distress associated with ES symptoms. Excessive sleepiness was reported by 27.8% (95% CI, 27.1%-28.5%) of the sample. Excessive sleepiness with associated symptoms was found in 15.6% of the participants (95% CI, 15.0%-16.2%). Adding an ES frequency of at least 3 times per week for at least 3 months despite normal sleep duration dropped the prevalence to 4.7% of the sample (95% CI, 4.4%-5.0%). The proportion of individuals having social or professional impairment and psychological distress increased with the frequency of ES symptoms during the week and within the same day. In multivariate models, the number of ES episodes per day and severity of ES were identified as the best predictors for impairment/distress. Prevalence of hypersomnia disorder was 1.5% of the participants (95% CI, 1.3%-1.7%). The most common coexisting conditions were mood and substance use disorders. Excessive sleepiness is an important problem in the US population, even when using restrictive criteria to define it. Hypersomnia disorder is more prevalent than previously estimated. Excessive sleepiness has to be recognized and given attention by

  9. Cell cycle stage dependent variations in drug-induced topoisomerase II mediated DNA cleavage and cytotoxicity

    International Nuclear Information System (INIS)

    Estey, E.; Adlakha, R.C.; Hittelman, W.N.; Zwelling, L.A.

    1987-01-01

    The DNA cleavage produced by 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) in mammalian cells is putatively mediated by topoisomerase II. The authors found that in synchronized HeLa cells the frequency of such cleavage was 4-15-fold greater in mitosis than in S while the DNA of G 1 and G 2 cells exhibited an intermediate susceptibility to cleavage. The hypersensitivity of mitotic DNA to m-AMSA-induced cleavage was acquired relatively abruptly in late G 2 and was lost similarly abruptly in early G 1 . The susceptibility of mitotic cells to m-AMSA-induced DNA cleavage was not clearly paralleled by an increase in topoisomerase II activity in 350 mM NaCl extracts from mitotic cells compared to similar extracts from cells in G 1 , S, or G 2 . Furthermore, equal amounts of decatenating activity from cells in mitosis and S produced equal amounts of m-AMSA-induced cleavage of simian virus 40 (SV40) DNA; i.e., the interaction between m-AMSA and extractable enzyme was similar in mitosis and S. The DNA of mitotic cells was also hypersensitive to cleavage by 4'-demethylepipodophyllotoxin 4-(4,6-O-ethylidene-β-D-glucopyranoside) (etoposide), a drug that produces topoisomerase II mediated DNA cleavage without binding to DNA. Cell cycle stage dependent fluctuations in m-AMSA-induced DNA cleavage may result from fluctuations in the structure of chromatin per se that occur during the cell cycle. Surprisingly, cell cycle stage dependent differences in m-AMSA-induced DNA cleavage did not correlate with differences in the susceptibility to the cytotoxic effects of the drug. In fact, cells in S were most sensitive to these effects. These results are an exception to the previously observed parallel between the susceptibility of mammalian cells to drug-induced DNA cleavage and the susceptibility of the cells to drug-induced cytotoxicity and indicate the complexity of any relationship between the two phenomena

  10. Drug-induced interstitial lung diseases. Often forgotten; Medikamenteninduzierte interstitielle Lungenerkrankungen. Haeufig vergessen

    Energy Technology Data Exchange (ETDEWEB)

    Poschenrieder, F.; Stroszczynski, C. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Hamer, O.W. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Lungenfachklinik Donaustauf, Donaustauf (Germany)

    2014-12-15

    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.) [German] Medikamenteninduzierte interstitielle Lungenerkrankungen (engl. ''drug-induced interstitial lung diseases'', DILD) sind wahrscheinlich haeufiger, als sie diagnostiziert werden. Aufgrund ihrer potenziellen Reversibilitaet ist eine erhoehte Vigilanz gegenueber DILD auch seitens der Radiologie angebracht, da diese regelmaessig ein radiomorphologisches Korrelat in der hochaufloesenden Computertomographie (''high-resolution CT'', HRCT) der Lunge aufweisen. Typische, nach eigener Erfahrung relativ haeufige Manifestationsformen von DILD sind der diffuse Alveolarschaden (engl. ''diffuse alveolar damage'', DAD), die eosinophile Pneumonie (EP), die Hypersensitivitaetspneumonitis (HP), die organisierende

  11. Drug-induced anaphylactic reactions in Indian population: A systematic review

    Science.gov (United States)

    Patel, Tejas K.; Patel, Parvati B.; Barvaliya, Manish J.; Tripathi, C. B.

    2014-01-01

    Background: Epidemiological data on drug-induced anaphylactic reactions are limited in India and are largely depending on studies from developed countries. Aim: The aim was to analyze the published studies of drug-induced anaphylaxis reported from India in relation with causative drugs and other clinical characteristics. Materials and Methods: The electronic databases were searched for Indian publications from 1998 to 2013 describing anaphylactic reactions. The information was collected for demographics, set up in which anaphylaxis occurred, causative drugs, incubation period, clinical features, associated allergic conditions, past reactions, co-morbid conditions, skin testing, IgE assays, therapeutic intervention and mortality. Reactions were analyzed for severity, causality, and preventability. Data were extracted and summarized by absolute numbers, mean (95% confidence interval [CI]), percentages and odds ratio (OR) (95% CI). Results: From 3839 retrieved references, 52 references describing 54 reactions were included. The mean age was 35.31 (95% CI: 30.52–40.10) years. Total female patients were 61.11%. Majority reactions were developed in perioperative conditions (53.70%), ward (20.37%) and home (11.11%). The major incriminated groups were antimicrobials (18.52%), nonsteroidal antiinflammatory drugs-(NSAIDs) (12.96%) and neuromuscular blockers (12.96%). Common causative drugs were diclofenac (11.11%), atracurium (7.41%) and β-lactams (5.96%). Cardiovascular (98.15%) and respiratory (81.48%) symptoms dominated the presentation. Skin tests and IgE assays were performed in 37.03% and 18.52% cases, respectively. The fatal cases were associated with complications (OR =5.04; 95% CI: 1.41–17.92), cerebral hypoxic damage (OR =6.80; 95% CI: 2.14–21.58) and preventable reactions (OR =14.33; 95% CI: 2.33–87.97). Conclusion: Antimicrobials, NSAIDs, and neuromuscular blockers are common causative groups. The most fatal cases can be prevented by avoiding allergen

  12. MicroRNA changes in rat mesentery and serum associated with drug-induced vascular injury

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Roberta A., E-mail: Roberta.A.Thomas@gsk.com; Scicchitano, Marshall S.; Mirabile, Rosanna C.; Chau, Nancy T.; Frazier, Kendall S.; Thomas, Heath C.

    2012-08-01

    Regulatory miRNAs play a role in vascular biology and are involved in biochemical and molecular pathways dysregulated during vascular injury. Collection and integration of functional miRNA data into these pathways can provide insight into pathogenesis at the site of injury; the same technologies applied to biofluids may provide diagnostic or surrogate biomarkers. miRNA was analyzed from mesentery and serum from rats given vasculotoxic compounds for 4 days. Fenoldopam, dopamine and midodrine each alter hemodynamics and are associated with histologic evidence of vascular injury, while yohimbine is vasoactive but does not cause histologic evidence of vascular injury in rat. There were 38 and 35 miRNAs altered in a statistically significant manner with a fold change of 2 or greater in mesenteries of fenoldopam- and dopamine-dosed rats, respectively, with 9 of these miRNAs shared. 10 miRNAs were altered in rats given midodrine; 6 were shared with either fenoldopam or dopamine. In situ hybridization demonstrated strong expression and co-localization of miR-134 in affected but not in adjacent unaffected vessels. Mesenteric miRNA expression may provide clarity or avenues of research into mechanisms involved in vascular injury once the functional role of specific miRNAs becomes better characterized. 102 miRNAs were altered in serum from rats with drug-induced vascular injury. 10 miRNAs were commonly altered in serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these 102 were also altered in mesenteries from rats with drug-induced vascular injury, suggesting their possible utility as peripheral biomarkers. -- Highlights: ► Mesentery and serum were examined from rats given vasoactive compounds for 4 days. ► 72 miRNAs were altered in mesenteries from rats with vascular injury. ► miR-134 was localized to affected but not adjacent unaffected vessels. ► 102 miRNAs were changed in serum from rats with vascular injury. ► 18 miRNAs changed in both

  13. 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.

  14. 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

  15. 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.

  16. Prevalence of excessive sleepiness is higher whereas insomnia is lower with greater severity of obstructive sleep apnea.

    Science.gov (United States)

    Bjorvatn, Bjørn; Lehmann, Sverre; Gulati, Shashi; Aurlien, Harald; Pallesen, Ståle; Saxvig, Ingvild W

    2015-12-01

    The objective of the present study was to investigate the prevalence of insomnia and excessive sleepiness in relation to the presence and severity of obstructive sleep apnea (OSA). The sample consisted of patients referred to a university hospital on suspicion of OSA. In total, 1115 patients with mean age of 48 years were studied. Insomnia (Bergen Insomnia Scale) and excessive sleepiness (Epworth Sleepiness Scale) were diagnosed using validated questionnaires. The insomnia scale permits diagnosing insomnia using both old and new (from 2014) criteria. OSA was diagnosed and categorized based on a standard respiratory polygraphic sleep study using a type 3 portable monitor. OSA was diagnosed in 59.4 % of the referred patients. The prevalence of excessive sleepiness was higher with greater severity of OSA: 40.5 % in the patients without OSA (apnea-hypopnea index (AHI) insomnia using the 2014 diagnostic criteria showed an opposing prevalence: 54.2 % no OSA, 54.9 % mild OSA, 48.5 % moderate OSA, and 44.6 % severe OSA. Logistic and linear regression analyses showed that sleepiness was positively associated whereas insomnia was negatively associated with OSA severity and AHI. Both excessive sleepiness and insomnia were seen in high proportions of the patients referred on suspicion of OSA. Excessive sleepiness was higher whereas insomnia was lower with greater OSA severity.

  17. The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia.

    Science.gov (United States)

    Krysiak, Robert; Kowalcze, Karolina; Szkrobka, Witold; Okopien, Boguslaw

    2016-05-01

    In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia. The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55-3g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6months of treatment. Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups. The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  18. Drug-induced diseases (DIDs: An experience of a tertiary care teaching hospital from India

    Directory of Open Access Journals (Sweden)

    Vishal R Tandon

    2015-01-01

    Full Text Available Background & objectives: Drug-induced diseases (DIDs are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR data collected form Pharmacovigilance Programme of India (PvPI to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. Methods: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. Results: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99% accounted for maximum DIDs followed by adult (37.79% and paediatric (8.21%. Maximum events were probable (93.98% followed by possible (6.04%. All DIDs required intervention. Gastritis (7.43%, diarrhoea (5.92%, anaemia (4.79%, hypotension (2.77%, hepatic dysfunction (2.69%, hypertension (1.51%, myalgia (1.05%, and renal dysfunction (1.01% were some of the DIDs. Anti-tubercular treatment (ATT, anti- retroviral treatment (ART, ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. Interpretation & conclusions: Our findings show that DIDs are a significant health problem in our country, which need more attention.

  19. FXR antagonism of NSAIDs contributes to drug-induced liver injury identified by systems pharmacology approach

    Science.gov (United States)

    Lu, Weiqiang; Cheng, Feixiong; Jiang, Jing; Zhang, Chen; Deng, Xiaokang; Xu, Zhongyu; Zou, Shien; Shen, Xu; Tang, Yun; Huang, Jin

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are worldwide used drugs for analgesic, antipyretic, and anti-inflammatory therapeutics. However, NSAIDs often cause several serious liver injuries, such as drug-induced liver injury (DILI), and the molecular mechanisms of DILI have not been clearly elucidated. In this study, we developed a systems pharmacology approach to explore the mechanism-of-action of NSAIDs. We found that the Farnesoid X Receptor (FXR) antagonism of NSAIDs is a potential molecular mechanism of DILI through systematic network analysis and in vitro assays. Specially, the quantitative real-time PCR assay reveals that indomethacin and ibuprofen regulate FXR downstream target gene expression in HepG2 cells. Furthermore, the western blot shows that FXR antagonism by indomethacin induces the phosphorylation of STAT3 (signal transducer and activator of transcription 3), promotes the activation of caspase9, and finally causes DILI. In summary, our systems pharmacology approach provided novel insights into molecular mechanisms of DILI for NSAIDs, which may propel the ways toward the design of novel anti-inflammatory pharmacotherapeutics. PMID:25631039

  20. FXR antagonism of NSAIDs contributes to drug-induced liver injury identified by systems pharmacology approach.

    Science.gov (United States)

    Lu, Weiqiang; Cheng, Feixiong; Jiang, Jing; Zhang, Chen; Deng, Xiaokang; Xu, Zhongyu; Zou, Shien; Shen, Xu; Tang, Yun; Huang, Jin

    2015-01-29

    Non-steroidal anti-inflammatory drugs (NSAIDs) are worldwide used drugs for analgesic, antipyretic, and anti-inflammatory therapeutics. However, NSAIDs often cause several serious liver injuries, such as drug-induced liver injury (DILI), and the molecular mechanisms of DILI have not been clearly elucidated. In this study, we developed a systems pharmacology approach to explore the mechanism-of-action of NSAIDs. We found that the Farnesoid X Receptor (FXR) antagonism of NSAIDs is a potential molecular mechanism of DILI through systematic network analysis and in vitro assays. Specially, the quantitative real-time PCR assay reveals that indomethacin and ibuprofen regulate FXR downstream target gene expression in HepG2 cells. Furthermore, the western blot shows that FXR antagonism by indomethacin induces the phosphorylation of STAT3 (signal transducer and activator of transcription 3), promotes the activation of caspase9, and finally causes DILI. In summary, our systems pharmacology approach provided novel insights into molecular mechanisms of DILI for NSAIDs, which may propel the ways toward the design of novel anti-inflammatory pharmacotherapeutics.

  1. Generation of a Drug-inducible Reporter System to Study Cell Reprogramming in Human Cells*

    Science.gov (United States)

    Ruiz, Sergio; Panopoulos, Athanasia D.; Montserrat, Nuria; Multon, Marie-Christine; Daury, Aurélie; Rocher, Corinne; Spanakis, Emmanuel; Batchelder, Erika M.; Orsini, Cécile; Deleuze, Jean-François; Izpisua Belmonte, Juan Carlos

    2012-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells is achieved by the expression of defined transcription factors. In the last few years, reprogramming strategies on the basis of doxycycline-inducible lentiviruses in mouse cells became highly powerful for screening purposes when the expression of a GFP gene, driven by the reactivation of endogenous stem cell specific promoters, was used as a reprogramming reporter signal. However, similar reporter systems in human cells have not been generated. Here, we describe the derivation of drug-inducible human fibroblast-like cell lines that express different subsets of reprogramming factors containing a GFP gene under the expression of the endogenous OCT4 promoter. These cell lines can be used to screen functional substitutes for reprogramming factors or modifiers of reprogramming efficiency. As a proof of principle of this system, we performed a screening of a library of pluripotent-enriched microRNAs and identified hsa-miR-519a as a novel inducer of reprogramming efficiency. PMID:23019325

  2. Drug-induced sedation endoscopy (DISE) classification systems: a systematic review and meta-analysis.

    Science.gov (United States)

    Dijemeni, Esuabom; D'Amone, Gabriele; Gbati, Israel

    2017-12-01

    Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention. A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages. Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials. DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.

  3. Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report

    Directory of Open Access Journals (Sweden)

    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.

  4. Effect of physical stress on drug-induced sleep endoscopy for obstructive sleep apnea.

    Science.gov (United States)

    Park, Sang Min; Kim, Dong-Kyu

    2017-08-01

    Drug-induced sleep endoscopy (DISE) is a reliable upper airway evaluation tool, widely used to improve surgical results in patients with obstructive sleep apnea (OSA). Several factors, including sleeping position and depth of sedation, affect DISE findings. This study aimed to evaluate the impact of physical stress on DISE findings. Eighty-five patients with OSA underwent two DISE examinations at the same level of sedation. The "first DISE" (control group) was performed after polysomnography, while the "second DISE" (test group) performed immediately after a treadmill stress test. The two groups were compared for changes in degree and configuration of airway obstruction at the levels of the velum, oropharynx, tongue base, and epiglottis. There were several differences in DISE findings between the control and test groups. DISE findings obtained after the stress test revealed significant narrowing of multiple airway structures; upper airway narrowing was observed at the velum (19/48; 39.6%), oropharynx (31/63; 49.2%), and tongue base (9/61; 14.8%). Changes in configuration of upper airway obstruction were observed only at the level of the velum (33/85; 38.8%). Stress exercise test induces changes in the degree and configuration of upper airways narrowing, which causes surgeons to over or underestimate the obstructive pattern, depending on the clinical circumstance. When counseling patients on the likely value of sleep surgery based on DISE findings, stressful physical activity should be included as a contributing factor in treatment planning.

  5. Psychobiology of drug-induced religious experience: from the brain "locus of religion" to cognitive unbinding.

    Science.gov (United States)

    Nencini, Paolo; Grant, Kathleen A

    2010-11-01

    The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the "fitness" of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

  6. Periodic lateralized epileptiform discharges can survive anesthesia and result in asymmetric drug-induced burst suppression

    Directory of Open Access Journals (Sweden)

    Edward C. Mader Jr.

    2017-02-01

    Full Text Available Drug-induced burst suppression (DIBS is bihemispheric and bisymmetric in adults and older children. However, asymmetric DIBS may occur if a pathological process is affecting one hemisphere only or both hemispheres disproportionately. The usual suspect is a destructive lesion; an irritative or epileptogenic lesion is usually not invoked to explain DIBS asymmetry. We report the case of a 66-year-old woman with new-onset seizures who was found to have a hemorrhagic cavernoma and periodic lateralized epileptiform discharges (PLEDs in the right temporal region. After levetiracetam and before anesthetic antiepileptic drugs (AEDs were administered, the electroencephalogram (EEG showed continuous PLEDs over the right hemisphere with maximum voltage in the posterior temporal region. Focal electrographic seizures also occurred occasionally in the same location. Propofol resulted in bihemispheric, but not in bisymmetric, DIBS. Remnants or fragments of PLEDs that survived anesthesia increased the amplitude and complexity of the bursts in the right hemisphere leading to asymmetric DIBS. Phenytoin, lacosamide, ketamine, midazolam, and topiramate were administered at various times in the course of EEG monitoring, resulting in suppression of seizures but not of PLEDs. Ketamine and midazolam reduced the rate, amplitude, and complexity of PLEDs but only after producing substantial attenuation of all burst components. When all anesthetics were discontinued, the EEG reverted to the original preanesthesia pattern with continuous non-fragmented PLEDs. The fact that PLEDs can survive anesthesia and affect DIBS symmetry is a testament to the robustness of the neurodynamic processes underlying PLEDs.

  7. [Moderate potentially drug-induced hyponatremia in older adults: benefit in drug reduction].

    Science.gov (United States)

    Peyro Saint Paul, Laure; Martin, Jocelyne; Gaillard, Cathy; Mosquet, Brigitte; Coquerel, Antoine; de la Gastine, Blandine

    2013-01-01

    This study aimed at evaluating the benefit of changing drug therapy in elderly patients with moderate, potentially drug-induced hyponatremia. Hospitalized older adults, with moderate hyponatremia, potentially induced by drugs, were randomized into two arms: an interventional group, whose drug therapy was changed, and a reference group, which received standard care. The effectiveness of the intervention was evaluated by the normalization of serum sodium after four weeks and by the incidence of falls three months later. Nineteen patients were randomized, fourteen evaluated at 4 weeks. Serum sodium was normalized more frequently in the interventional group than in the reference group: 75% (6/8) IC95% [35-97] versus 0% (0/6) IC95% [0-46]; p=0.01. A greater reduction in falls occurred in the therapeutic intervention group 75% (3/4) IC95% [19-99] versus 0% (0/5) IC95% [0-52]; p=0.048. This study showed the biological and clinical benefit of a pharmalogical intervention. Registration number of the study: ID RCB 2010-A00778-31. © 2013 Société Française de Pharmacologie et de Thérapeutique.

  8. Comparison of drug-induced sleep endoscopy and lateral cephalometry in obstructive sleep apnea.

    Science.gov (United States)

    George, Jonathan R; Chung, Sooyoun; Nielsen, Ib; Goldberg, Andrew N; Miller, Arthur; Kezirian, Eric J

    2012-11-01

    To evaluate the association between findings from drug-induced sleep endoscopy (DISE) and lateral cephalometry in obstructive sleep apnea (OSA) STUDY DESIGN: Cross-sectional. This was a consecutive series of subjects with OSA who underwent DISE and lateral cephalometry. DISE findings were characterized according to the region/degree of obstruction as well as the VOTE classification (velum, oropharyngeal lateral walls, tongue, and epiglottis). The primary measurements from lateral cephalometry images were sella-nasion-point A angle, sella-nasion-point B angle, distance from the posterior nasal spine-tip of palate, posterior airway space, and mandibular plane to hyoid (MPH) distance, although additional airway measurements were taken. Descriptive statistics summarized DISE and lateral cephalometry findings, and χ(2) and t tests examined potential associations between their findings. Among the 55 subjects, most demonstrated velum-related obstruction, although obstruction related to other structures was also common. Lateral cephalometry findings were within population norms with the exception of an increased MPH and decreased airway 4 and airway 5 measurements. There was little association between DISE and lateral cephalometry findings, although significant associations were identified between tongue-related obstruction and airway measurements posterior to the tongue base. DISE and lateral cephalometry are largely distinct airway evaluation techniques in OSA. The use of these techniques remains complementary. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  9. Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network

    Science.gov (United States)

    Navarro, Victor J.; Barnhart, Huiman; Bonkovsky, Herbert L.; Davern, Timothy; Fontana, Robert J.; Grant, Lafaine; Reddy, K. Rajender; Seeff, Leonard B.; Serrano, Jose; Sherker, Averell H.; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

    2014-01-01

    Background The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity due to conventional medications as well as herbals and dietary supplements (HDS). Rationale To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight US referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury due to HDS. Hepatotoxicity due to HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments including death and liver transplantation were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury due to bodybuilding HDS, 85 due to non-bodybuilding HDS, and 709 due to medications. Main Results Liver injury due to HDS increased from 7% to 20% (p Bodybuilding HDS caused prolonged jaundice (median 91 days) in young men but did not result in any fatalities or liver transplantation. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women and more frequently led to death or transplantation compared to injury from medications (13% vs. 3%, p bodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes; death and transplantation. PMID:25043597

  10. Evaluation of acoustic characteristics of snoring sounds obtained during drug-induced sleep endoscopy.

    Science.gov (United States)

    Herzog, Michael; Plößl, Sebastian; Glien, Alexander; Herzog, Beatrice; Rohrmeier, Christian; Kühnel, Thomas; Plontke, Stefan; Kellner, Patrick

    2015-09-01

    Snoring sounds are discussed to contain acoustic information about their geneses. Nocturnal snoring can easily be recorded acoustically but it is difficult to visually verify its genesis. Contrary, snoring patterns induced by drug-induced sleep endoscopy (DISE) can be visually differentiated. The aim of the study was to classify patterns of obstructions and vibration during DISE and to evaluate acoustic characteristics between these different patterns of snoring. DISE was performed in 41 male patients with sleep-disordered breathing. The recorded video sequences (n = 108) were classified visually at a mute mode in different patterns of snoring (velar, velar obstructive, tonsillar, post-apnoeic). The sound tracks of these subgroups were analysed and compared with regard to the parameters sound pressure level, loudness, sharpness, roughness, fluctuations strength and centre frequency. Obstructive snoring patterns revealed a higher loudness than non-obstructive patterns (>25 sone). Velar snoring showed more roughness (>150 cAsper) than tonsillar and post-apnoeic snoring and revealed the lowest centre frequency (snoring presented the highest sharpness (>1.6 acum) whereas post-apnoeic snoring revealed the largest fluctuation strength (>50 cVacil). Different snoring patterns induced by DISE can be classified visually, and an approach to differentiate them acoustically by means of psychoacoustic analyses is demonstrated. On the basis of these results, nocturnal snoring might also be differentiated by psychoacoustic algorithms which could be implemented in acoustic polygraphic screening devices in the future.

  11. Investigation of the Source of Snoring Sound by Drug-Induced Sleep Nasendoscopy.

    Science.gov (United States)

    Xu, Hui-Jie; Jia, Rui-Fang; Yu, Hui; Gao, Zhan; Huang, Wei-Ning; Peng, Hao; Yang, Yi; Zhang, Lei

    2015-01-01

    To investigate the source of snoring sound in patients with simple snoring (SS) and different degrees of obstructive sleep apnea syndrome (OSAS) in order to provide a basis for the surgical treatment of snoring. Fifty-two patients with either SS or OSAS (with an apnea-hypopnea index ≤40) underwent drug-induced sleep nasendoscopy (DISN). Vibration sites in the pharyngeal cavity were observed. Vibration of the soft palate, pharyngeal lateral wall, epiglottis, and tongue base appeared in 100, 53.8, 42.3, and 26.9% of the patients, respectively. The source of snoring sound was divided into two types: palatal fluttering only (type I) and multisite vibration (type II). The latter was divided into 3 subtypes: palatal fluttering with epiglottis vibration (type IIa), palatal fluttering with lateral wall vibration (type IIb), and palatal fluttering with vibration of the lateral wall, epiglottis, and tongue base together (type IIc). The distribution of type I snoring was the highest in SS patients. Type IIb was more common in patients with medium and severe OSAS. Type IIc was most common in patients with severe OSAS. The source of snoring sound is diverse, with SS and OSAS patients showing different features. DISN is a very effective method of identifying the snoring source. © 2015 S. Karger AG, Basel.

  12. The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

    Science.gov (United States)

    Lan, Ming-Chin; Hsu, Yen-Bin; Lan, Ming-Ying; Huang, Yun-Chen; Kao, Ming-Chang; Huang, Tung-Tsun; Chiu, Tsan-Jen; Yang, Mei-Chen

    2017-12-15

    The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P titration level (P titration level and any other collapse at the tongue base or epiglottis. By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

  13. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy.

    Science.gov (United States)

    Montero, Joan; Sarosiek, Kristopher A; DeAngelo, Joseph D; Maertens, Ophélia; Ryan, Jeremy; Ercan, Dalia; Piao, Huiying; Horowitz, Neil S; Berkowitz, Ross S; Matulonis, Ursula; Jänne, Pasi A; Amrein, Philip C; Cichowski, Karen; Drapkin, Ronny; Letai, Anthony

    2015-02-26

    There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient's living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion ("priming") induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clinical experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Disease-related and drug-induced skin manifestations in inflammatory bowel disease.

    Science.gov (United States)

    Hindryckx, Pieter; Novak, Gregor; Costanzo, Antonio; Danese, Silvio

    2017-03-01

    Skin manifestations are common in patients with inflammatory bowel diseases (IBD) and can be part of a concomitant illness with a shared genetic background, an extra-intestinal manifestation of the disease, or a drug side-effect. Areas covered: We provide a practical overview of the epidemiology, pathogenesis, diagnosis, therapeutic approach and prognosis of the most frequent disease-related and drug-induced cutaneous manifestations in IBD, illustrated by cases encountered in our clinical practice. Among the most frequently encountered IBD-related lesions are erythema nodosum, pyoderma gangrenosum and Sweet's syndrome. Common skin manifestations with a strong association to TNF antagonists are local injection site reactions, psoriasiform lesions, cutaneous infections, vasculitides and lupus-like syndromes. In addition, we discuss the relation of thiopurines and TNF antagonists with the risk of skin cancer. Expert commentary: We hope this review will help caretakers involved in the management of IBD patients to recognize the lesions and to manage them in close collaboration with a dedicated dermatologist.

  15. Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources

    Science.gov (United States)

    Bicalho, Millena Drumond; Soares, Danielly Botelho; Botoni, Fernando Antonio; Reis, Adriano Max Moreira; Martins, Maria Auxiliadora Parreiras

    2015-01-01

    Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX®, UpToDate®, Medscape® and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss’ kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211–0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292–0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality. PMID:26371029

  16. Chinese Skullcap in Move Free Arthritis Supplement Causes Drug Induced Liver Injury and Pulmonary Infiltrates

    Directory of Open Access Journals (Sweden)

    Renumathy Dhanasekaran

    2013-01-01

    Full Text Available Herbal medications are being increasingly used by the American population especially for common conditions like arthritis. They have been reported to cause adverse effects, including significant hepatotoxicity, but reporting remains sporadic. We report here a patient who developed drug induced liver injury following the intake of Move Free, which is an over-the-counter arthritis supplement. We propose that Chinese skullcap, which is one of the herbal ingredients of the medication, is responsible for the adverse event. There was a strong temporal association between the intake of supplement and onset of symptoms, and also there have been a few recent case reports implicating the same component. A unique observation in our case is the occurrence of pulmonary infiltrates simultaneously with the hepatotoxicity, and this side effect has not been well documented before. Both the hepatic and pulmonary complications completely resolved over few weeks after the patient stopped taking the medication. Since these supplements are readily available over the counter, we feel that it is important to document possible adverse outcomes to raise awareness in the medical community and also among patients.

  17. [Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations].

    Science.gov (United States)

    Zhu, Yun; Liu, Shu-hong; Wang, Jia-bo; Song, Hai-bo; Li, Yong-gang; He, Ting-ting; Ma, Xiao; Wang, Zhong-xia; Wang-Li-ping; Zhou, Kun; Bai, Yun-feng; Zou, Zheng-sheng; Xiao, Xiao-he

    2015-12-01

    To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations. A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed. Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died. Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.

  18. Pharmacy Students' Learning and Satisfaction With High-Fidelity Simulation to Teach Drug-Induced Dyspepsia

    Science.gov (United States)

    2013-01-01

    Objective. To assess second-year pharmacy students’ acquisition of pharmacotherapy knowledge and clinical competence from participation in a high-fidelity simulation, and to determine the impact on the simulation experience of implementing feedback from previous students. Design. A high-fidelity simulation was used to present a patient case scenario of drug-induced dyspepsia with gastrointestinal bleeding. The simulation was revised based on feedback from a previous class of students to include a smaller group size, provision of session material to students in advance, and an improved learning environment. Assessment. Student performance on pre- and post-simulation knowledge and clinical competence tests documented significant improvements in students' knowledge of dyspepsia and associated symptoms, with the greatest improvement on questions relating to the hemodynamic effects of gastrointestinal bleeding. Students were more satisfied with the simulation experience compared to students in the earlier study. Conclusion. Participation in a high-fidelity simulation allowed pharmacy students to apply knowledge and skills learned in the classroom. Improved student satisfaction with the simulation suggests that implementing feedback obtained through student course evaluations can be an effective means of improving the curriculum. PMID:23519773

  19. Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses.

    Science.gov (United States)

    Parlow, J; Viale, J P; Annat, G; Hughson, R; Quintin, L

    1995-05-01

    We compared two methods of assessment of baroreflex sensitivity in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangents taken at the resting pressure of each of these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r = .96, P < .001), with significant but similar intraindividual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r = .69 to .83). The spontaneous baroreflex method provides a reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.

  20. Nocturnal sleep, daytime sleepiness and fatigue in fibromyalgia patients compared to rheumatoid arthritis patients and healthy controls: a preliminary study.

    Science.gov (United States)

    Roehrs, Timothy; Diederichs, Christina; Gillis, Mazy; Burger, Amanda J; Stout, Rebecca A; Lumley, Mark A; Roth, Thomas

    2013-01-01

    Fibromyalgia (FM) and rheumatoid arthritis (RA) are pain disorders, both of which are associated with complaints of sleep disturbance, non-refreshing sleep, and daytime sleepiness and fatigue. Given the putative differential central versus peripheral nervous system involvement in these disorders, subjective and objective measures of nocturnal sleep, daytime sleepiness, fatigue and pain were compared between patient groups and to healthy controls (HC). Fifty women (18 with FM, 16 with RA, and 16 HC) completed an 8h nocturnal polysomnogram (NPSG), Multiple Sleep Latency Test (MSLT) the following day, and self-reports of sleepiness, fatigue, and pain. FM and RA patients were similar to each other and had less total sleep time than HC, primarily due to more wake after sleep onset. In an analysis of sleep and wake bouts, both patient groups had longer duration of wake bouts than HC. Nocturnal sleep was judged to be non-restorative for both patient groups. Although reporting the greatest subjective sleepiness and fatigue, FM patients had less objective (MSLT) daytime sleepiness than HC, whereas RA patients were intermediate in objective sleepiness. Unlike the RA and HC, FM patients also showed no association between their subjective and objective sleepiness. Women with FM have similar nocturnal sleep disturbance as those with RA, but FM patients report greater self-rated daytime sleepiness and fatigue than RA and HC, which did not correspond to the relatively low level of objectively determined daytime sleepiness of FM patients. These findings suggest a generalized hyperarousal state in FM. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Effect of biliopancreatic diversion on sleep quality and daytime sleepiness in patients with obesity and type 2 diabetes.

    Science.gov (United States)

    Mello, Mayra; Vasques, Ana Carolina J; Pareja, José C; Oliveira, Maria da S de; Novaes, Fernanda S; Chaim, Élinton A; Geloneze, Bruno

    2017-12-01

    The poor quality of sleep and the deprivation thereof have been associated with disruption of metabolic homeostasis, favoring the development of obesity and type 2 diabetes (T2DM). We aimed to evaluate the influence of biliopancreatic diversion (BPD) surgery on sleep quality and excessive daytime sleepiness of obese patients with T2DM, comparing them with two control groups consisting of obese and normal weight individuals, both normal glucose tolerant. Forty-two women were divided into three groups: LeanControl (n = 11), ObeseControl (n = 13), and ObeseT2DM (n = 18). The LeanC and ObeseC groups underwent all tests and evaluations once. The ObeseT2DM underwent BPD and were reassessed after 12 months. Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were applied before and 12 months after BPD. Before surgery, there was less daytime sleepiness in LeanC group (p = 0.013) compared with ObeseC and T2DMObese groups. The two obese groups did not differ regarding daytime sleepiness, demonstrating that the presence of T2DM had no influence on daytime sleepiness. After surgery, the daytime sleepiness (p = 0.002) and the sleep quality (p = 0.033) improved. The score for daytime sleepiness of operated T2DMObese group became similar to LeanC and lower than ObeseC (p = 0.047). BPD surgery has positively influenced daytime sleepiness and sleep quality of obese patients with T2DM, leading to normalization of daytime sleepiness 12 months after surgery. These results reinforce previously identified associations between sleep, obesity and T2DM in view of the importance of sleep in metabolic homeostasis, quality of life and health.

  2. 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.

  3. 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

  4. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia.

    Science.gov (United States)

    Togo, Fumiharu; Natelson, Benjamin H; Cherniack, Neil S; FitzGibbons, Jennifer; Garcon, Carmen; Rapoport, David M

    2008-01-01

    We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal. We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase. CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night's sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group. CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a

  5. Hospitalized pediatric antituberculosis drug induced hepatotoxicity: Experience of an Indonesian referral hospital

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2017-05-01

    Full Text Available Objective: To determine the characteristics and risk factors of pediatric antituberculosis drug induced hepatotoxicity (ADIH in Dr. Hasan Sadikin Hospital, a referral hospital in West Java, Indonesia. Methods: Medical records of hospitalized pediatric ADIH from October 2010 to October 2015 were reviewed retrospectively through computer-based search. Descriptive data were presented as percentage. Analytical case-control study on characteristics of ADIH was conducted using Chi-square and Mann Whitney test. Results: Fifty (3.5% out of 1 424 pediatric TB patients developed ADIH; 20 (40% were boys and 30 (60% girls. More than half were under 5 years old and 33 (66% were malnourished. ADIH occured in 29 (58% cases treated for pulmonary TB, 15 (30% for extrapulmonary TB and 6 (12% for both; 34 cases (68% occured during the intensive phase. We identified hepatic comorbidities including CMV infection [1 (2%] and typhoid [1 (2%], and other diseases treated by hepatotoxic drugs such as chemotherapeutic drugs, antiepileptics, and antiretroviral drugs [9 (18%]. Case-control analysis of 50 ADIH cases and 100 TB controls without ADIH showed that the correlation between gender, age, type of TB, nutritional status and comorbidities to occurence of ADIH was statistically insignificant (P = 0.26, 0.765, 0.495, 0.534 9 and 0.336, respectively. Pediatric ADIH was treated using modified British Thoracic Society guidelines. Conclusions: Pediatric ADIH in our hospital is quite frequent, thus identifying risk factors and development of pediatric guideline is mandatory. Further study is needed to identify other risk factors such as genetic acetylator status.

  6. [Case reports of drug-induced liver injury in a reference hospital of Zulia state, Venezuela].

    Science.gov (United States)

    Mengual-Moreno, Edgardo; Lizarzábal-García, Maribel; Ruiz-Soler, María; Silva-Suarez, Niniveth; Andrade-Bellido, Raúl; Lucena-González, Maribel; Bessone, Fernando; Hernández, Nelia; Sánchez, Adriana; Medina-Cáliz, Inmaculada

    2015-03-01

    Drug-induced liver injury (DILI) is an important cause of morbidity and mortality worldwide, with varied geographical differences. The aim of this prospective, descriptive, cross-sectional study was to identify and characterize cases of DILI in a hospital of Zulia state, Venezuela. Thirteen patients with a presumptive diagnosis of DILI attended by the Department of Gastroenterology, Hospital Universitario, Zulia state, Venezuela, from December-2012 to December-2013 were studied. Ibuprofen (n = 3; 23.1%), acetaminophen (n = 3; 23.1), isoniazid (n = 2; 15.4%) and Herbalife products (n = 2; 15.4%) were the main drugs involved with DILI. Acetaminophen and ibuprofen showed a mixed pattern of liver injury (n = 3; 23.1%) and isoniazid presented a hepatocellular pattern (n = 2; 15.4%). The CIOMS/RUCAMS allowed the identification of possible (n = 7; 53.9%), probable (n = 4; 30.8%) and highly-probable cases (n = 2; 15.4%) of DILI. Amoxicillin/clavulanate, isoniazid, isotretinoin, methotrexate and Herbalife nutritional products were implicated as highly-probable and probable agents. The highest percentage of DILI corresponded to mild cases that recovered after the discontinuation of the agent involved (n = 9; 69.3%). The consumption of Herbalife botanical products is associated with probable causality and fatality (n = 1; 7.7%). In conclusion, the frequency of DILI cases controlled by the Department of Gastroenterology of the Hospital Universitario of Maracaibo was low, being ibuprofen, acetaminophen, isoniazid and products Herbalife the products most commonly involved. It is recommended to continue with the prospective registration of cases, with an extended follow up monitoring period and to facilitate the incorporation of other hospitals in the Zulia State and Venezuela.

  7. 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

  8. Effect of lipid molecule headgroup mismatch on non steroidal anti-inflammatory drugs induced membrane fusion.

    Science.gov (United States)

    Mondal Roy, Sutapa; Sarkar, Munna

    2011-12-20

    Membrane fusion is an essential process guiding many important biological events, which most commonly requires the aid of proteins and peptides as fusogenic agents. Small drug induced fusion at low drug concentration is a rare event. Only three drugs, namely, meloxicam (Mx), piroxicam (Px), and tenoxicam (Tx), belonging to the oxicam group of non steroidal anti-inflammatory drugs (NSAIDs) have been shown by us to induce membrane fusion successfully at low drug concentration. A better elucidation of the mechanism and the effect of different parameters in modulating the fusion process will allow the use of these common drugs to induce and control membrane fusion in various biochemical processes. In this study, we monitor the effect of lipid headgroup size mismatch in the bilayer on oxicam NSAIDs induced membrane fusion, by introducing dimyristoylphosphatidylethanolamine (DMPE) in dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles (SUVs). Such headgroup mismatch affects various lipid parameters which includes inhibition of trans-bilayer motion, domain formation, decrease in curvature, etc. Changes in various lipidic parameters introduce defects in the membrane bilayer and thereby modulate membrane fusion. SUVs formed by DMPC with increasing DMPE content (10, 20, and 30 mol %) were used as simple model membranes. Transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) were used to characterize the DMPC-DMPE mixed vesicles. Fluorescence assays were used to probe the time dependence of lipid mixing, content mixing, and leakage and also used to determine the partitioning of the drugs in the membrane bilayer. How the inhibition of trans-bilayer motion, heterogeneous distribution of lipids, decrease in vesicle curvature, etc., arising due to headgroup mismatch affect the fusion process has been isolated and identified here. Mx amplifies these effects maximally followed by Px and Tx. This has been correlated to the enhanced

  9. 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.

  10. Exploring BSEP Inhibition-Mediated Toxicity with a Mechanistic Model of Drug-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Jeffrey L Woodhead

    2014-11-01

    Full Text Available Inhibition of the bile salt export pump (BSEP has been linked to incidence of drug-induced liver injury (DILI, presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to explore whether we can predict that hepatotoxic BSEP inhibitors can cause bile acid accumulation to reach toxic levels. We also simulate bosentan in rats in order to illuminate potential reasons behind the lack of toxicity in rats compared to the toxicity observed in humans. DILIsym® predicts that bosentan, but not telmisartan, will cause mild hepatocellular ATP decline and serum ALT elevation in a simulated population of humans. The difference in hepatotoxic potential between bosentan and telmisartan is consistent with clinical observations. However, DILIsym® underpredicts the incidence of bosentan toxicity. DILIsym® also predicts that bosentan will not cause toxicity in a simulated population of rats, and that the difference between the response to bosentan in rats and in humans is primarily due to the less toxic bile acid pool in rats. Our simulations also suggest a potential synergistic role for bile acid accumulation and mitochondrial electron transport chain inhibition in producing the observed toxicity in CP-724,714, and suggest that CP-724,714 metabolites may also play a role in the observed toxicity. Our work also compares the impact of competitive and noncompetitive BSEP inhibition for CP-724,714 and demonstrates that noncompetitive inhibition leads to much greater bile acid accumulation and potential toxicity. Our research demonstrates the potential for mechanistic modeling to contribute to the understanding of how bile acid transport inhibitors

  11. Quantification of Drug-Induced mRNA in Human Whole Blood

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    Masato Mitsuhashi

    2008-01-01

    Full Text Available Apoptosis was induced in heparinized human whole blood by 3 different ways (radiation, bleomycin, or etoposide, and various mRNA were quantified using the method we reported (Clin. Chem. 2006; 52:634-642. We found that cyclin-dependent kinase inhibitor 1A (p21 and p53 upregulated modulator of apoptosis (PUMA were the most sensitive and universal mRNA markers of apoptosis in leukocytes. In order to define positive and negative responses, a synthetic RNA was spiked into the lysis buffer and the fold increase was calculated. As a result, 837/880 (95.1% of data points stayed between 0.75 and 1.5 fold increase, and 874/880 (99.3% were within 0.5-2.0 fold increase. When blood samples from 40 healthy adults were stimulated with 22 different drugs, more than 75% of the samples responded to bleomycin (1 μM, idarubicin (2 μM, vincristine (1 μM, daunorubicin (2 μM, cytarabine (10 μM, to induce p21 and/or PUMA mRNA, and approximately 25% showed no induction. Significant correlation was found between p21 and PUMA mRNA responses, and between daunorubicin and cytarabine, idarubicin, and vincristine for both p21 and PUMA. The quantification of drug-induced mRNA in whole blood will be considered as ex vivo , and is a suitable platform for biomarker screening as well as a model system for drug sensitivity tests in future.

  12. Drug induced mortality: a multiple cause approach on Italian causes of death Register

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    Francesco Grippo

    2015-04-01

    Full Text Available Background: Drug-related mortality is a complex phenomenon that has several health, social and economic effects. In this paper trends of drug-induced mortality in Italy are analysed. Two approaches have been followed: the traditional analysis of the underlying cause of death (UC (data refers to the Istat mortality database from 1980 to 2011, and the multiple cause (MCanalysis, that is the analysis of all conditions reported on the death certificate (data for 2003-2011 period.Methods: Data presented in this paper are based on the Italian mortality register. The selection of Icd codes used for the analysis follows the definition of the European Monitoring Centre for Drugs and Drug Addiction. Using different indicators (crude and standardized rates, ratio multiple to underlying, the results obtained from the two approaches (UC and MC have been compared. Moreover, as a measure of association between drug-related causes and specific conditions on the death certificate, an estimation of the age-standardized relative risk (RR has been used.Results: In the years 2009-2011, the total number of certificates whit mention of drug use was 1,293, 60% higher than the number UC based. The groups of conditions more strongly associated with drug-related causes are the mental and behavioral disorders (especially alcohol consumption, viral hepatitis, cirrhosis and fibrosis of liver, AIDS and endocarditis.Conclusions : The analysis based on multiple cause approach shows, for the first time, a more detailed picture of the drug related death; it allows to better describe the mortality profiles and to re-evaluate  the contribution of a specific cause to death.

  13. Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report.

    Science.gov (United States)

    Brănișteanu, Daciana Elena; Ianoşi, Simona Laura; Dimitriu, Andreea; Stoleriu, Gabriela; Oanţǎ, Alexandru; Brănișteanu, Daniel Constantin

    2018-01-01

    syndrome lesions, which was drug-induced.

  14. Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints.

    Science.gov (United States)

    Kim, Eunyoung; Nam, Hojung

    2017-05-31

    Drug-induced liver injury (DILI) is a critical issue in drug development because DILI causes failures in clinical trials and the withdrawal of approved drugs from the market. There have been many attempts to predict the risk of DILI based on in vivo and in silico identification of hepatotoxic compounds. In the current study, we propose the in silico prediction model predicting DILI using weighted molecular fingerprints. In this study, we used 881 bits of molecular fingerprint and used as features describing presence or absence of each substructure of compounds. Then, the Bayesian probability of each substructure was calculated and labeled (positive or negative for DILI), and a weighted fingerprint was determined from the ratio of DILI-positive to DILI-negative probability values. Using weighted fingerprint features, the prediction models were trained and evaluated with the Random Forest (RF) and Support Vector Machine (SVM) algorithms. The constructed models yielded accuracies of 73.8% and 72.6%, AUCs of 0.791 and 0.768 in cross-validation. In independent tests, models achieved accuracies of 60.1% and 61.1% for RF and SVM, respectively. The results validated that weighted features helped increase overall performance of prediction models. The constructed models were further applied to the prediction of natural compounds in herbs to identify DILI potential, and 13,996 unique herbal compounds were predicted as DILI-positive with the SVM model. The prediction models with weighted features increased the performance compared to non-weighted models. Moreover, we predicted the DILI potential of herbs with the best performed model, and the prediction results suggest that many herbal compounds could have potential to be DILI. We can thus infer that taking natural products without detailed references about the relevant pathways may be dangerous. Considering the frequency of use of compounds in natural herbs and their increased application in drug development, DILI labeling

  15. Is periodontal health a predictor of drug-induced gingival overgrowth? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ruchi Banthia

    2014-01-01

    Full Text Available Background: Gingival overgrowth is a common side-effect of amlodipine regimen on the oral cavity. There is controversy regarding the cause and effect relationship of periodontal health and drug induced gingival overgrowth. Therefore, this study was conducted to investigate and to assess the relationship between the periodontal health and the onset and severity of gingival overgrowth in hypertensive patients receiving amlodipine. Materials and Methods: A total of 99 known hypertensive patients on amlodipine regimen were included in this study. Probing pocket depth (PPD and clinical attachment loss (CAL were noted on four sites of maxillary and mandibular anterior teeth. Gingival enlargement scores were assessed for each patient by employing the hyperplastic index. Oral hygiene status was evaluated using the calculus index (CI. Patients were divided into H, E and L groups based on their periodontal status and responders and non-responders based on their hyperplastic index scores. Differences in means of different periodontal variables in different groups were tested for significance by using ANOVA and unpaired Student t-test. Pearson′s correlation coefficient was calculated to assess the correlation between different variables. For all analyses, P < 0.05 was considered to be significant. Results: All the periodontal parameters were statistically highly significant (P = 0.00 amongst H, E and L groups and between responders and non-responders. Statistically highly significant Pearson correlation coefficients were found between mean PPD and mean hyperplastic score, mean CAL and mean hyperplastic score and mean calculus and mean hyperplastic score. Conclusion: The results of this study indicated a definite association between periodontal health and development and severity of amlodipine-induced gingival overgrowth

  16. Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution.

    Science.gov (United States)

    Millière, Raphaël

    2017-01-01

    There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as "drug-induced ego dissolution (DIED)", for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the "minimal" or "embodied" self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other

  17. Drug-induced lupus: simvastatin or amiodarone? A case report in elderly

    Directory of Open Access Journals (Sweden)

    Mauro Turrin

    2013-03-01

    Full Text Available Reports of systemic lupus erythematosus (SLE seen during treatment with amiodarone are rare in the literature. SLE or immunological abnormalities induced by treatment with statins are more frequent. In this issue we report a case of a 81-year-old male who, after a 2-year therapy with amiodarone, developed a clinical and serologic picture of drug-induced SLE (DILE. He was admitted for congestive heart failure in mechanical aortic valve prosthesis, permanent atrial fibrillation (anticoagulation with warfarin, hypercholesterolaemia, and hypothyroidism. Amiodarone was started two years earlier for polymorphic ventricular tachycardia, statin and L-thyroxine the following year. At admission he presented pleuro-pericardical effusion detected by CT-scan (also indicative of interstitial lung involvement and echocardiography. Serological main indicative findings were: elevation of inflammatory markers, ANA (Anti-Nuclear Antibodies titers = 1:320 (indirect immune-fluorescence – IIF – assay on HEp-2, homogeneous/fine speckled pattern, anti-dsDNA titers = 1:80 (IIF on Crithidia luciliae, negative ENA (Extractable Nuclear Antigens and antibodies anti-citrulline, rheumatoid factor = 253 KU/l, normal C3-C4, negative HbsAg and anti-HCV, negative anticardiolipin antibodies IgG and IgM, negative anti-beta2GPI IgG and IgM. Amiodarone was discontinued and methylprednisolone was started, since the patient was severely ill. At discharge, after a month, the patient was better and pleuro-pericardical effusion was reduced. Readmitted few weeks later for bradyarithmia and worsening of dyspnoea, pericardial effusion was further reduced but he died for refractory congestive heart failure and pneumonia. Clinical picture (sierositis, neither skin nor kidney involvement, other typical side effects of amiodarone (hypothyroidism and lung interstitial pathology and serological findings are suggestive of amiodarone-induced SLE.

  18. A predictive ligand-based Bayesian model for human drug-induced liver injury.

    Science.gov (United States)

    Ekins, Sean; Williams, Antony J; Xu, Jinghai J

    2010-12-01

    Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds that cause idiosyncratic hepatotoxicity. In the current study, we applied machine learning, a Bayesian modeling method with extended connectivity fingerprints and other interpretable descriptors. The model that was developed and internally validated (using a training set of 295 compounds) was then applied to a large test set relative to the training set (237 compounds) for external validation. The resulting concordance of 60%, sensitivity of 56%, and specificity of 67% were comparable to results for internal validation. The Bayesian model with extended connectivity functional class fingerprints of maximum diameter 6 (ECFC_6) and interpretable descriptors suggested several substructures that are chemically reactive and may also be important for DILI-causing compounds, e.g., ketones, diols, and α-methyl styrene type structures. Using Smiles Arbitrary Target Specification (SMARTS) filters published by several pharmaceutical companies, we evaluated whether such reactive substructures could be readily detected by any of the published filters. It was apparent that the most stringent filters used in this study, such as the Abbott alerts, which captures thiol traps and other compounds, may be of use in identifying DILI-causing compounds (sensitivity 67%). A significant outcome of the present study is that we provide predictions for many compounds that cause DILI by using the knowledge we have available from previous studies. These computational models may represent cost-effective selection criteria before in vitro or in vivo experimental studies.

  19. Drug-induced QT interval prolongation: does ethnicity of the thorough QT study population matter?

    Science.gov (United States)

    Shah, Rashmi R

    2013-02-01

    Inter-ethnic differences in drug responses have been well documented. Drug-induced QT interval prolongation is a major safety concern and therefore, regulatory authorities recommend a clinical thorough QT study (TQT) to investigate new drugs for their QT-prolonging potential. A positive study, determined by breach of a preset regulatory threshold, significantly influences late phase clinical trials by requiring intense ECG monitoring. A few studies that are currently available, although not statistically conclusive at present, question the assumption that ethnicity of the study population may not influence the outcome of a TQT study. Collective consideration of available pharmacogenetic and clinical information suggests that there may be inter-ethnic differences in QT-prolonging effects of drugs and that Caucasians may be more sensitive than other populations. The information also suggest s that (a) these differences may depend on the QT-prolonging potency of the drug and (b) exposure-response (E-R) analysis may be more sensitive than simple changes in QT(c) interval in unmasking this difference. If the QT response in Caucasians is generally found to be more intense than in non-Caucasians, there may be significant regulatory implications for domestic acceptance of data from a TQT study conducted in foreign populations. However, each drug will warrant an individual consideration when extrapolating the results of a TQT study from one ethnic population to another and the ultimate clinical relevance of any difference. Further adequately designed and powered studies, investigating the pharmacologic properties and E-R relationships of additional drugs with different potencies, are needed in Caucasians, Oriental/Asian and African populations before firm conclusions can be drawn. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  20. 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

  1. 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

    Determine if defining two subtypes of sleep-disordered breathing (SDB) events - with or without hypoxia - results in measures that are more strongly associated with hypertension and sleepiness. A total of 1,022 subjects with 2,112 nocturnal polysomnograms (PSGs) from the Wisconsin Sleep Cohort were...... 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...... 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...

  2. Mood states and sleepiness in college students: influences of age, sex, habitual sleep, and substance use.

    Science.gov (United States)

    Jean-Louis, G; von Gizycki, H; Zizi, F; Nunes, J

    1998-10-01

    Survey and laboratory evidence suggests several factors affecting sleep-wake patterns of college students. These factors include social and academic demands, diminution of parental guidance, reduction of total sleep time, delayed bedtime, and increased nap episodes. In this study, we examined the problem of falling asleep in school as a correlate of negative moods in this population (N = 294). A multivariate analysis showed significant main effects of sleepiness on mood states based on the Profile of Mood States. Students who fell asleep in school reported higher negative mood states. Significant interactions were observed among sleepiness and age, sex, race, and duration of sleep. Specifically, younger men reported higher negative moods. No interactions were noted for alcohol and marijuana consumption; however, students who fell asleep in school consumed more alcoholic beverages and smoked more than those who did not. Perhaps falling asleep in school could be used as an index that characterizes students who manifest adaptive or psychological difficulty.

  3. [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.

  4. 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.

  5. 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

  6. 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.

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

    Science.gov (United States)

    Bajpai, Geetika; Shukla, Garima; Pandey, Ravindra M; Gupta, Anupama; Afsar, Mohammed; Goyal, Vinay; Srivastava, Achal; Behari, Madhuri

    2016-01-01

    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. 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). 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. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Prevalence of poor sleep quality, sleepiness and obstructive sleep apnoea risk factors in athletes.

    Science.gov (United States)

    Swinbourne, Richard; Gill, Nicholas; Vaile, Joanna; Smart, Daniel

    2016-10-01

    Despite the perceived importance of sleep for athletes, little is known regarding athlete sleep quality, their prevalence of daytime sleepiness or risk factors for obstructive sleep apnoea (OSA) such as snoring and witnessed apnoeic episodes. The purpose of the present study was to characterise normative sleep quality among highly trained team sport athletes. 175 elite or highly trained rugby sevens, rugby union and cricket athletes completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Quality of Life questionnaires and an OSA risk factor screen. On average, athletes reported 7.9 ± 1.3 h of sleep per night. The average PSQI score was 5.9 ± 2.6, and 50% of athletes were found to be poor sleepers (PSQI > 5). Daytime sleepiness was prevalent throughout the population (average global score of 8.5) and clinically significant (ESS score of ≥10) in 28% of athletes. OSA may be an important clinical consideration within athletic populations, as a considerable number of athletes (38%) defined themselves as snorers and 8% reported having a witnessed apnoeic episode. The relationship between self-rated sleep quality and actual PSQI score was strong (Pearson correlation of 0.4 ± 0.1, 90% confidence limits). These findings suggest that this cohort of team sport athletes suffer a preponderance of poor sleep quality, with associated high levels of daytime sleepiness. Athletes should receive education about how to improve sleep wake schedules, extend total sleep time and improve sleep quality.

  12. Medico-legal aspects of sleep disorders: sleepiness and civil liability.

    Science.gov (United States)

    Ellis, Elizabeth; Grunstein, Ronald R.

    2001-02-01

    Excessive sleepiness is associated with motor vehicle accidents and is responsible for enormous social and financial loss. The specific legal obligations for an individual with a sleep disorder, their employer and those health care practitioners associated with that individual are reviewed. Although there are related implications within the criminal law and in particular criminal negligence, the arguments developed in this paper will be largely confined to the context of the civil liability. The legal concepts of foreseeability and proximity are discussed in the context of sleep-related accidents. The reasoning of a recent Australian High Court judgement is discussed in view of the differences in legal and medical opinion on the extent of foreseeability of accidents as a result of sleepiness. Many countries have legislation designed to protect employees from injury at work and to protect the general public from injury. What is not clear is the extent to which an employer will be required to accept liability for an employee's sleepiness and the duty to monitor the health of their employees. Factors which influence this liability include: the extent to which the implications of the condition is known and understood generally; the extent to which the condition is suspected or identified in an individual employee; the extent of a proper screening and treatment program and the way in which risk management programs have been implemented. Although the issue of sleepiness and civil liability is examined from an Australian legal context, the principles have direct relevance to other legal systems. The authors highlight the degree of uncertainty provided by the common law and statutory provisions, and that decisions rest on the balance of public interests, which mean that many of the current dilemmas facing practitioners may only be solved in the courts.

  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. 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.

  15. Is nocturnal epilepsy cause of disturbed quality of sleep and elevated daytime sleepiness?

    Science.gov (United States)

    Klobucníková, Katariná; Carnická, Zuzana; Wagnerová, Helená; Siarnik, Pavel

    2014-01-01

    Authors evaluated quality of sleep and daytime vigilance in patients with nocturnal epilepsy and compared it to those with daytime epilepsy. Nocturnal seizures are an important type of epilepsy. They can result in morbidity due to disruption of sleep architecture. Daytime sleepiness, as a serious consequence of nocturnal seizures, has negative influence on quality of life in patients with epilepsy. Authors examined 100 patients with epilepsy. The occurrence of epileptic seizures in circadian rhythm, type of epilepsy and epileptic seizures, as well as aetiology of epilepsy were evaluated. Patients were divided in two groups, 17 patients with nocturnal epilepsy and 83 patients with epileptic seizures not related to sleep. All of them underwent overnight video-EEG-polysomnography and they filled in the Epworth Sleepiness Scale questionnaire (ESS) as well as The Pittsburgh Sleep Quality Index questionnaire (PSQI). Overnight video-EEG-polysomnography detected significant changes in the sleep architecture in patients with nocturnal epilepsy. Significant decrease of N3 stage of NREM sleep (14.31%±8.07 in the group of nocturnal epilepsy vs. 20.12%±9.24 in the group of daytime epilepsy, p=0.01). Concurrently, significantly poorer sleep quality according to PSQI (18.52±7.51 in the group of nocturnal epilepsy vs. 6.21±3.62 in the group of daytime epilepsy, p=0.01) and tendency to increased daytime sleepiness according to ESS was revealed in these patients. Remarkable changes in sleep architecture associated with poor quality of sleep and increased daytime sleepiness were detected in patients with nocturnal epilepsy. In conclusion, we emphasize the importance of sleep history taking in patients with epilepsy and their further evaluation in sleep laboratory.

  16. Drug-induced Liver Injury is Frequently Associated with Severe Cutaneous Adverse Drug Reactions: Experience from Two Australian Tertiary Hospitals.

    Science.gov (United States)

    Fang, Wendy C; Adler, Nikki R; Graudins, Linda V; Goldblatt, Caitlin; Goh, Michelle Sy; Roberts, Stuart K; Trubiano, Jason A; Aung, Ar Kar

    2018-01-08

    Drug-induced liver injury can be associated with certain cutaneous adverse drug reactions. We aim to demonstrate the prevalence of drug-induced liver injury in patients with cutaneous adverse drug reactions. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. A retrospective cohort study of patients with cutaneous adverse drug reactions was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. 104 patients with cutaneous adverse drug reactions were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with Stevens-Johnson syndrome (OR=6.0, 95% CI:1.8-19.7, p=0.003). Antimicrobials were the most common class to be implicated in drug-induced liver injury. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs. 11 days, p=0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. Drug-induced liver injury commonly occurs in patients with cutaneous adverse drug reactions and is associated with longer inpatient stay. Patients with Stevens-Johnson/toxic epidermal necrolysis and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury. This article is protected by copyright. All rights reserved.

  17. Role of miRNA and its potential as a novel diagnostic biomarker in drug-induced liver injury.

    Science.gov (United States)

    Sanjay, Sukumaran; Girish, Chandrashekaran

    2017-04-01

    MicroRNAs (miRNA or miR) are the most abundant and stable class of small RNA. Unlike the typical RNA molecules present in the cell, they do not encode proteins but can control translation. and Hhence, they are found to play a major role in the regulation of cellular processes. miRNAs have been shown to differentially regulate various genes, and the expression levels of some miRNAs changes several fold in liver and serum, during drug- induced toxicity. This review summarises some of the latest findings about the biological functions of miRNA and its potential use as diagnostic biomarkers in drug- induced liver injury. The information presented in this article is taken from published literature, both original work and reviews on mechanisms of drug- induced liver injury, miRNA in liver pathophysiology, and studies exploring the use of miRNA as biomarker in drug- induced liver injury. Literature search was done using search engines:- PUBMED, Google scholar, and relevant journal sites. Recent research provides insight into the ability of miRNA to regulate various pathways in diseased and nondiseased states of liver. They also lay a foundation for development of diagnostic tests utilizing the potential of miRNAs that can not only be used for early detection of DILI but also to differentiate between different types of DILI. More studies on biological functions of miRNA and standardisation of protocol between research laboratories can lead to further advancement in this field. Considering the therapeutic and diagnostic potential of miRNA, the major challenge would be to integrate these findings to clinical settings where it can be used for the treatment of cases with DILI.

  18. 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.

  19. MicroRNA-122:a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity

    OpenAIRE

    Kia, Richard; Kelly, Lorna; Sison-Young, Rowena L C; Zhang, Fang; Pridgeon, Chris S; Heslop, James A; Metcalfe, Pete; Kitteringham, Neil R; Baxter, Melissa; Harrison, Sean; Hanley, Neil A; Burke, Zoë D; Storm, Mike P; Welham, Melanie J; Tosh, David

    2015-01-01

    Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated...

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

    Science.gov (United States)

    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.

  1. [Connective tissue growth factors, CTGF and Cyr61 in drug-induced gingival overgrowth--an animal model].

    Science.gov (United States)

    Ciobanică, Mihaela; Cianga, Corina; Căruntu, Irina-Draga; Grigore, Georgiana; Cianga, P

    2008-01-01

    Human gingival overgrowth may occur as a side effect of chronic administration of some therapeutic agents. The mechanisms responsible for the gingival tissues lesions, fibrosis and inflamation, involve an impaired balance between the production and the degradation of type I collagen. It has been demonstrated that CCN2/CTGF, a connective tissue growth factor, is highly expressed in the gingival tissues and positively correlated with the degree of fibrosis in the drug-induced gingival overgrowth. The aim of this study was to identify the presence and localization of CCN2/CTGF and CCN1/Cyr61, members of the same molecular family, in gingival tissues of cyclosporin A- and nifedipine-treated rats, by immunohistochemistry. Staining was evaluated with light microscope and the results show cellular and extracellular CTGF in nifedipin gingival overgrowth tissues with intensity of labeling higher compared to the CsA gingival overgrowth tissues or the controls. The staining for Cyr61 shows its intracellular localization with no diference of labeling intensity between drug-induced gingival overgrowth and normal tissues. Also, we were interested in the gingival TGF-â expression in those animals. We didn't find any commercial anti-rat TGF antibody and our anti-human antibody shows no cross-reactivity with rat tissues. The data from our study sustain the involvement of CTGF and Cyr61 as growth factors in the gingival tissues and the CTGF association with drug-induced gingival overgrowth.

  2. Activation of JNK triggers release of Brd4 from mitotic chromosomes and mediates protection from drug-induced mitotic stress.

    Directory of Open Access Journals (Sweden)

    Akira Nishiyama

    Full Text Available Some anti-cancer drugs, including those that alter microtubule dynamics target mitotic cells and induce apoptosis in some cell types. However, such drugs elicit protective responses in other cell types allowing cells to escape from drug-induced mitotic inhibition. Cells with a faulty protective mechanism undergo defective mitosis, leading to genome instability. Brd4 is a double bromodomain protein that remains on chromosomes during mitosis. However, Brd4 is released from mitotic chromosomes when cells are exposed to anti-mitotic drugs including nocodazole. Neither the mechanisms, nor the biological significance of drug-induced Brd4 release has been fully understood. We found that deletion of the internal C-terminal region abolished nocodazole induced Brd4 release from mouse P19 cells. Furthermore, cells expressing truncated Brd4, unable to dissociate from chromosomes were blocked from mitotic progression and failed to complete cell division. We also found that pharmacological and peptide inhibitors of the c-jun-N-terminal kinases (JNK pathway, but not inhibitors of other MAP kinases, prevented release of Brd4 from chromosomes. The JNK inhibitor that blocked Brd4 release also blocked mitotic progression. Further supporting the role of JNK in Brd4 release, JNK2-/- embryonic fibroblasts were defective in Brd4 release and sustained greater inhibition of cell growth after nocodazole treatment. In sum, activation of JNK pathway triggers release of Brd4 from chromosomes upon nocodazole treatment, which mediates a protective response designed to minimize drug-induced mitotic stress.

  3. Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

    Directory of Open Access Journals (Sweden)

    Yifeng Guo

    Full Text Available Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4 play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A with drug-induced liver injury (DILI in Chinese renal transplantation (RT recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040, was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618; the frequency of haplotype ACGG was significantly higher in the DILI group (68.9% than in the non-DILI group (61.1% (p = 0.041. In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage.

  4. The Art and Science of Diagnosing and Managing Drug-induced Liver Injury in 2015 and Beyond.

    Science.gov (United States)

    Lewis, James H

    2015-11-01

    Drug-induced liver injury (DILI) remains a leading reason why new compounds are dropped from further study or are the subject of product warnings and regulatory actions. Hy's Law of drug-induced hepatocellular jaundice causing a case-fatality rate or need for transplant of 10% or higher has been validated in several large national registries, including the ongoing, prospective U.S. Drug-Induced Liver Injury Network. It serves as the basis for stopping rules in clinical trials and in clinical practice. Because DILI can mimic all known causes of acute and chronic liver disease, establishing causality can be difficult. Histopathologic findings are often nonspecific and rarely, if ever, considered pathognomonic. A daily drug dose >50-100 mg is more likely to be hepatotoxic than does management of DILI have recently been published, although specific therapies remain limited. The LiverTox Web site has been introduced as an interactive online virtual textbook that makes the latest information on more than 650 agents available to clinicians, regulators, and drug developers alike. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Fluorescent nanoprobe for in-vivo ratiometric imaging of endogenous hydrogen peroxide resulted from drug-induced organ damages.

    Science.gov (United States)

    Peng, Jin; Hou, Xianfeng; Zeng, Fang; Wu, Shuizhu

    2017-08-15

    Drug-induced organ damages have been considered as a grave problem regarding public health; hence effective method for in vivo detection of drug-induced organ damages is of great significance. Herein we developed a ratiometric fluorescent nanoprobe (NPs-A), which was prepared by loading the probe molecules into phospholipid bilayer, for assaying hydrogen peroxide (H 2 O 2 , an organ damage biomarker) level in vivo. The photophysical behavior of the probe molecule depends on the electron-withdrawing ability of the group at the 6- position of anthracene ring, on which the recognition moiety for hydrogen peroxide (dicarbonyl coupled with nitrophenyl, referred to as nitrophenyl-dicarbonyl) was introduced. Upon the reaction of the probe with H 2 O 2 , nitrophenyl-dicarbonyl group transforms into carboxyl group, and due to the variation of the electron-withdrawing ability of the 6th substituent, the fluorescent properties of the probe molecule alters accordingly, thus ensuring the ratiometric detection for H 2 O 2 with high selectivity with the detection limit of 0.49μM. In addition, the nanoprobe (NPs-A) was applied for cell and in vivo imaging applications; and the results indicate that it can detect and track the level of H 2 O 2 in living cells and to monitor and spatially map endogenous H 2 O 2 levels in a drug-induced organ damage model of zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prevention and treatment of vaginal bleeding after drug-induced abortion by Yaoliuan capsule and its effects on menses recovery.

    Science.gov (United States)

    Jin, Zhichun; Huang, Guangying

    2005-01-01

    In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Risky drug use and effects on sleep quality and daytime sleepiness.

    Science.gov (United States)

    Ogeil, Rowan P; Phillips, James G; Rajaratnam, Shantha M W; Broadbear, Jillian H

    2015-09-01

    Sleep problems are commonly reported following alcohol and cannabis abuse, but our understanding of sleep in non-clinical drug using populations is limited. The present study examined the sleep characteristics of alcohol and cannabis users recruited from the wider community. Two hundred forty-eight self-identified alcohol and/or cannabis users (131 women and 117 men) with a mean age of 26.41 years completed an online study that was advertised via online forums, print media and flyers. As part of the study, participants completed validated sleep scales assessing sleep quality (Pittsburgh Sleep Quality Index) and excessive daytime sleepiness (Epworth Sleepiness Scale) in addition to validated drug scales assessing alcohol (Alcohol Use Disorders Identification Test) and cannabis (Marijuana Screening Inventory) use. Problems with sleep quality were more commonly reported than were complaints of excessive daytime sleepiness. Clinically significant poor sleep quality was associated with comorbid problem alcohol and cannabis use. Women reporting problem alcohol and cannabis use had poorer sleep outcomes than men. Social drug users who report risky alcohol and cannabis use also report poor sleep. Poor sleep quality likely exacerbates any drug-associated problems in non-clinical populations. Copyright © 2015 John Wiley & Sons, Ltd.

  10. 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

    To evaluate whether daytime sleepiness, poor sleep quality, and morningness and eveningness preferences are associated with common mental disorders (CMDs) among college students. A total of 963 college students completed self-administered questionnaires that collected information about sociodemographic characteristics, sleep quality characteristics, CMDs, and other lifestyle behaviors. The prevalence of CMDs was 24.3% (95% confidence interval [CI] [21.5%, 27.1%]) among all students. Prevalence estimates of both excessive daytime sleepiness and poor sleep quality were higher among females (35.4% and 54.4%) than males (22.0% and 45.8%). Cigarette smoking was statistically significantly and positively associated with having CMDs (p = .034). Excessive daytime sleepiness (odds ratio [OR] = 3.65; 95% CI [2.56, 4.91]) and poor sleep quality (OR = 4.76; 95% CI [3.11, 7.29]) were associated with increased odds of CMDs. Given the adverse health consequences associated with both sleep disorders and CMDs, improving sleep hygiene among college students is imperative to public health.

  11. 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.

  12. 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.

  13. 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

  14. Which diagnostic findings in disorders with excessive daytime sleepiness are really helpful? A retrospective study.

    Science.gov (United States)

    Kretzschmar, Ute; Werth, Esther; Sturzenegger, Christian; Khatami, Ramin; Bassetti, Claudio L; Baumann, Christian R

    2016-06-01

    Due to extensive clinical and electrophysiological overlaps, the correct diagnosis of disorders with excessive daytime sleepiness is often challenging. The aim of this study was to provide diagnostic measures that help discriminating such disorders, and to identify parameters, which don't. In this single-center study, we retrospectively identified consecutive treatment-naïve patients who suffered from excessive daytime sleepiness, and analyzed clinical and electrophysiological measures in those patients in whom a doubtless final diagnosis could be made. Of 588 patients, 287 reported subjective excessive daytime sleepiness. Obstructive sleep apnea is the only disorder that could be identified by polysomnography alone. The diagnosis of insufficient sleep syndrome relies on actigraphy as patients underestimate their sleep need and the disorder shares several clinical and electrophysiological properties with both narcolepsy type 1 and idiopathic hypersomnia. Sleep stage sequencing on MSLT appears helpful to discriminate between insufficient sleep syndrome and narcolepsy. Sleep inertia is a strong indicator for idiopathic hypersomnia. There are no distinctive electrophysiological findings for the diagnosis of restless legs syndrome. Altogether, EDS disorders are common in neurological sleep laboratories, but usually cannot be diagnosed based on PSG and MSLT findings alone. The diagnostic value of actigraphy recordings can hardly be overestimated. © 2016 European Sleep Research Society.

  15. Hippocampus volume and subjective sleepiness in older people with sleep-disordered breathing: a preliminary report.

    Science.gov (United States)

    Sforza, Emilia; Celle, Sébastien; Saint-Martin, Magali; Barthélémy, Jean C; Roche, Frédéric

    2016-04-01

    Sleep-disordered breathing (SDB) is associated with excessive daytime sleepiness (EDS) and explained by sleep fragmentation and hypoxaemia, both contributing to brain morphology abnormalities. Recent data on middle-aged SDB patients suggest a link between hippocampus volume (HV) and EDS. We tested this hypothesis in a group of SDB older subjects. A total of 232 healthy participants aged 75 ± 0.9 years were examined. Subjective EDS was assessed by the Epworth Sleep Questionnaire (ESS), with a mean score of 5.6 ± 3.5. Volumetric segmentation of the right (RHV) and left HV (LHV) were measured using FreeSurfer software. All subjects underwent extensive cognitive testing to exclude neurological disease, as well as ambulatory polygraphy to assess SDB status. Sleepy subjects showed a lower HV. In a correlation analysis, RHV (r = -0.162, P = 0.01) and LHV (r = -170, P = 0.05) were correlated negatively with ESS and not associated with respiratory data. Multiple regression analysis did not reveal any effect of age, gender, SDB severity and hypoxia. ESS was the only factor possibly explaining the lower RHV (P = -0.03) and LHV (P = -0.04). In older people with SDB, the subjective EDS was associated with lower HV. This morphological finding should be considered on the pathogenesis of sleepiness in SDB patients. NCT 00759304 and NCT 00766584. © 2015 European Sleep Research Society.

  16. [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.

  17. Regularity of cardiac rhythm as a marker of sleepiness in sleep disordered breathing.

    Directory of Open Access Journals (Sweden)

    Marc Guaita

    Full Text Available The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV to detect sleep disordered breathing (SDB patients with and without excessive daytime sleepiness (EDS before sleep onset.Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT and Multiple Sleep Latency Test (MSLT research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests.Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band and CORR (in Total band yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients.The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset.

  18. Regularity of cardiac rhythm as a marker of sleepiness in sleep disordered breathing.

    Science.gov (United States)

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

    2015-01-01

    The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV) to detect sleep disordered breathing (SDB) patients with and without excessive daytime sleepiness (EDS) before sleep onset. Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests. Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band) yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients. The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset.

  19. 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.

  20. 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.

  1. Sleep Quality and Daytime Sleepiness Among Women With Urgency Predominant Urinary Incontinence.

    Science.gov (United States)

    Winkelman, William D; Warsi, Ann; Huang, Alison J; Schembri, Michael; Rogers, Rebecca G; Richter, Holly E; Myers, Deborah L; Kraus, Stephen R; Johnson, Karen C; Hess, Rachel; Gregory, Thomas; Bradley, Catherine S; Arya, Lily A; Brown, Jeanette S; Stone, Katie L; Subak, Leslee L

    The objective of this study was to examine the strength and direction of the association between urinary symptoms and both poor quality sleep and daytime sleepiness among women with urgency urinary incontinence. A planned secondary analysis of baseline characteristics of participants in a multicenter, double-blinded, 12-week randomized controlled trial of pharmacologic therapy for urgency-predominant urinary incontinence in ambulatory women self-diagnosed by the 3 Incontinence Questions was performed. Urinary symptoms were assessed by 3-day voiding diaries. Quality of sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness using the Epworth Sleepiness Scale. Of the 640 participants, mean (SD) age was 56 (±14) years and 68% were white. Participants reported an average of 3.9 (±3.0) urgency incontinence episodes per day and 1.3 (±1.3) episodes of nocturia per night. At baseline, 57% had poor sleep quality (PSQI score, >5) and 17% reported daytime sleepiness (Epworth Sleepiness Scale score, >10). Most women (69%) did not use sleeping medication during the prior month, whereas 13% reported use of sleeping medication 3 or more times per week. An increase in total daily incontinence episodes, total daily urgency incontinence episodes, total daily micturitions, and moderate to severe urge sensations were all associated with higher self-report of poor sleep quality according to the PSQI (all P ≤ 0.01). Higher scores on the Bother Scale and the Health-Related Quality of Life for overactive bladder on the Overactive Bladder Questionnaire were similarly associated with higher rates of poor sleep quality (both P ≤ 0.01). In subgroup analysis of those who took sleeping medications less than twice a week, there was still a significant relationship between incontinence measures and quality of sleep as measured by the PSQI. In multivariable analyses, greater frequency of nighttime urgency incontinence was associated with poor sleep quality

  2. Sonolência e acidentes automobilísticos Sleepiness and motor vehicle accidents

    Directory of Open Access Journals (Sweden)

    SIMONE FAGONDES CANANI

    2001-03-01

    Full Text Available Objetivo: Este artigo tem por finalidade apresentar uma sucinta revisão sobre as repercussões da sonolência excessiva no desempenho dos motoristas no trânsito, enfatizando a necessidade da maior valorização do tema abordado. Métodos: Revisão bibliográfica da literatura nacional e internacional, abrangendo artigos originais e publicações oficiais da American Thoracic Society e da American Sleep Apnea Association. Resultados: As evidências de que a sonolência é um fator que pode contribuir de forma decisiva para a ocorrência de acidentes automobilísticos são crescentes. As dificuldades com relação à caracterização da sonolência precedendo o acidente são discutidas no texto. Muitas são as causas de sonolência excessiva; felizmente, sua maioria é passível de identificação e manejo adequado. Conclusões: É importante que haja maior entendimento do problema em nosso meio, para que possam ocorrer modificações na abordagem do paciente com sonolência excessiva e também discussões acerca das leis de trânsito vigentes e das obrigações legais do médico com relação a este problema.Objective: The purpose of this article is to present a brief review of the effects of excessive sleepiness on driving performance, and to emphasize the importance of the subject. Methods: Bibliographic review of national and international literature, including original articles and official publications from the American Thoracic Society and the American Sleep Apnea Association. Results: There is growing evidence that excessive sleepiness may be an important factor related to the occurrence of motor vehicle accidents. Difficulties regarding the identification of sleepiness as a preceding factor related to motor vehicle crashes are discussed on the text. There are many causes for excessive sleepiness. Fortunately most of them are easy to recognize and have specific treatment. Conclusions: A better understanding of the problem is fundamental

  3. 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

  4. Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

    Directory of Open Access Journals (Sweden)

    Raphaël Millière

    2017-05-01

    Full Text Available There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR. While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves

  5. Drug-induced gingival hyperplasia: a retrospective study using spontaneous reporting system databases.

    Science.gov (United States)

    Hatahira, Haruna; Abe, Junko; Hane, Yuuki; Matsui, Toshinobu; Sasaoka, Sayaka; Motooka, Yumi; Hasegawa, Shiori; Fukuda, Akiho; Naganuma, Misa; Ohmori, Tomofumi; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2017-01-01

    Drug-induced gingival hyperplasia (DIGH) causes problems with chewing, aesthetics, and pronunciation, and leads to the deterioration of the patient's quality of life (QOL). Thus, the aim of this study was to evaluate the incidence of DIGH using spontaneous reporting system (SRS) databases. We analyzed reports of DIGH from SRS databases and calculated the reporting odds ratios (RORs) of suspected drugs (immunosuppressants, calcium channel blockers, and anticonvulsants). The SRS databases used were the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database. With the data, we evaluated the time-to-onset profile and the hazard type using the Weibull shape parameter (WSP). Furthermore, we used the association rule mining technique to discover undetected relationships such as possible risk factors. The FAERS contained 5,821,716 reports. The RORs (95% confidence interval: CI) for cyclosporine, everolimus, sirolimus, mycophenolate mofetil, amlodipine, nifedipine, carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, and valproic acid, were 39.4 (95% CI: 30.3-51.2), 4.2 (1.7-10.0), 6.6 (2.5-17.7), 13.1 (7.2-23.2), 94.8 (80.0-112.9), 57.9 (35.7-94.0), 15.1 (10.3-22.3), 65.4 (33.8-126.7), 6.5 (3.6-11.8), 19.7 (8.8-44.0), 65.4 (52.4-82.9), 56.5 (21.1-151.7), 2.9 (1.1-7.7), and 17.5 (12.6-24.4), respectively. The JADER database contained 430,587 reports. The median time-to-onset of gingival hyperplasia values for immunosuppressants, calcium channel blockers, and anticonvulsants use were 71, 262, and 37 days, respectively. Furthermore, the 95% CI of the WSP β for anticonvulsants was over and excluded 1, which meant that they were wear-out failure type. Our results suggest that DIGH monitoring of patients administered immunosuppressants, calcium channel blockers, or anticonvulsants is important. We demonstrated the potential risk of DIGH following the long

  6. Pharmaka mit negativer Auswirkung auf den Knochen durch Medikamente induzierte Osteoporose // Medications with Negative Effect on Bone Drug-Induced Osteoporosis

    OpenAIRE

    Gasser RW; Götsch C

    2016-01-01

    Drug-induced osteoporosis may occur as a side effect of many commonly prescribed drugs. This leads to a disturbance of bone remodelling, which ultimately results in a preponderance of bone loss and as a consequence in an increased incidence of bone fractures. Also, a drug-induced disturbance of the calcium metabolism may contribute to bone mineral loss. Glucocorticoids, thyroxine, depot-medroxyprogesterone acetate, aromatase inhibitors, GnRH agonists, thiazolidinediones, proton pump inh...

  7. 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

    2013-01-01

    Study Objectives: To determine the relationship between sleep complaints, primary insomnia, excessive daytime sleepiness, and lifestyle factors in a large community-based sample. Design: Cross-sectional study. Setting: Blood donor sites in New Zealand. Patients or Participants: 22,389 individuals aged 16-84 years volunteering to donate blood. Interventions: N/A. Measurements: 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. Results: One in three participants report sleep, 5 or more nights per week, and 60% would like more sleep. Almost half the participants (45%) report suffering the symptoms of insomnia at least once per week, with one in 5 meeting more stringent criteria for primary insomnia. Excessive daytime sleepiness (evident in 9% of this large, predominantly 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. Conclusions: 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. Citation: Wilsmore BR; Grunstein RR; Fransen M; Woodward M; Norton R; Ameratunga S. Sleep habits, insomnia, and daytime sleepiness in a large and healthy

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

    2017-09-01

    Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing.

    Science.gov (United States)

    Atalla, Angela; Carlisle, Thomas W; Simonds, Anita K; Cowie, Martin R; Morrell, Mary J

    2017-06-01

    Patients with heart failure (HF) and sleep disordered breathing (SDB) are typically not sleepy, unlike patients without heart failure. Previous work in HF patients with obstructive SDB suggested that sleepiness was associated with a reduction in daytime activity. The consequences of predominately central SDB on sleepiness in HF are less well understood. The aim of this study was to test the hypothesis that subjective sleepiness is associated with reduced daytime activity in HF patients with central SDB, compared to those without SDB. The Epworth Sleepiness Scale (ESS), nocturnal polysomnography, and 14 days of wrist watch actigraphy were used to assess subjective daytime sleepiness, nocturnal sleep and breathing, and 24-h activity levels, respectively. A total of 54 patients with HF were studied, nine had obstructive SDB and were removed from further analysis. Of the patients, 23 had HF with predominantly central SDB (HF-CSA; apnea-hypopnea index (AHI) median 20.6 (IQR 12.9-40.2)/h), and 22 had noSDB (HF-noSDB; AHI 3.7 (2.5-5.9)/h). The median patient age was 68 years (range 59-73 years). There were no significant differences either in ESS score (HF-CSA; 8 [4-10] vs. HF-noSDB; 8 (6-12); p = 0.49) or in duration of daytime activity (HF-CSA 14.5 (14.1-15.2) and HF-noSDB 15.1 (14.4-15.3) hours; p = 0.10) between the groups. HF patients with predominately central SDB are not subjectively sleepy compared to those without SDB, despite reduced sleep quality. We speculate that the lack of sleepiness (based on ESS score) may be due to increased sympathetic nerve activity, although further studies are needed due to the small number (n = 5) of sleepy HF-CSA patients. Daytime activity was not different between HF-noSDB and HF-CSA patients. Copyright © 2017. Published by Elsevier B.V.

  15. Oral Appliance Therapy in Patients With Daytime Sleepiness and Snoring or Mild to Moderate Sleep Apnea: A Randomized Clinical Trial.

    Science.gov (United States)

    Marklund, Marie; Carlberg, Bo; Forsgren, Lars; Olsson, Tommy; Stenlund, Hans; Franklin, Karl A

    2015-08-01

    Oral appliances that move the mandible forward during sleep are suggested as treatment for mild to moderate obstructive sleep apnea. To test whether an adjustable, custom-made oral appliance improves daytime sleepiness and quality of life in patients with daytime sleepiness and snoring or mild to moderate obstructive sleep apnea. Ninety-six patients with daytime sleepiness and an apnea-hypopnea index (AHI) lower than 30 were included in a randomized, placebo-controlled, parallel trial in Umeå, Sweden, from May 2007 through August 2011. Four months' intervention with an oral appliance or a placebo device. Daytime sleepiness was measured with the Epworth Sleepiness Scale, the Karolinska Sleepiness Scale, and the Oxford Sleep Resistance (OSLER) test. Quality of life was assessed with the Short-Form 36-Item Health Survey (SF-36) and the Functional Outcomes of Sleep Questionnaire (FOSQ). Secondary outcomes included the apnea-hypopnea index, headaches, symptoms of restless legs, and insomnia. Oral appliance therapy was not associated with improvements in daytime sleepiness from baseline to 4-month follow-up when compared with the placebo device; Epworth score >10: 53% at baseline to 24% at follow-up for the oral appliance group vs 54% at baseline to 40% at follow-up for the placebo device group, P = .11; median (IQR) for Karolinska score ≥7/wk: 10 (8 to 14) at baseline to 7 (4 to 9) at follow-up for the oral appliance group vs 12 (6 to 15) at baseline to 8 (5 to 12) at follow-up for the placebo device group, P = .11; mean between-group difference in OSLER test, -2.4 min (95% CI, -6.3 to 1.4). The mean between-group difference for the total FOSQ score was insignificant (-1.2 [95% CI, -2.5 to 0.1]). No domain of the SF-36 differed significantly between the groups. The AHI was below 5 in 49% of patients using the active appliance and in 11% using placebo, with an odds ratio of 7.8 (95% CI, 2.6-23.5) and a number needed to treat of 3. Snoring (P oral appliance

  16. Decoupling of Sleepiness from Sleep Time and Intensity during Chronic Sleep Restriction: Evidence for a Role of the Adenosine System

    Science.gov (United States)

    Kim, Youngsoo; Bolortuya, Yunren; Chen, Lichao; Basheer, Radhika; McCarley, Robert W.; Strecker, Robert E.

    2012-01-01

    Study Objective: Sleep responses to chronic sleep restriction (CSR) might be very different from those observed after short-term total sleep deprivation. For example, after sleep restriction continues for several consecutive days, animals no longer express compensatory increases in daily sleep time and sleep intensity. However, it is unknown if these allostatic, or adaptive, sleep responses to CSR are paralleled by behavioral and neurochemical measures of sleepiness. Design: This study was designed to investigate CSR-induced changes in (1) sleep time and intensity as a measure of electrophysiological sleepiness, (2) sleep latency as a measure of behavioral sleepiness, and (3) brain adenosine A1 (A1R) and A2a receptor (A2aR) mRNA levels as a putative neurochemical correlate of sleepiness. Subjects: Male Sprague-Dawley rats Interventions: A 5-day sleep restriction (SR) protocol consisting of 18-h sleep deprivation and 6-h sleep opportunity each day. Measurement and Results: Unlike the first SR day, rats did not sleep longer or deeper on days 2 through 5, even though they exhibited significant elevations of behavioral sleepiness throughout all 5 SR days. For all SR days and recovery day 1, A1R mRNA in the basal forebrain was maintained at elevated levels, whereas A2aR mRNA in the frontal cortex was maintained at reduced levels. Conclusion: CSR leads to a decoupling of sleepiness from sleep time and sleep intensity, suggesting that there are at least two different sleep regulatory systems: one mediating sleepiness (homeostatic) and the other mediating sleep time/intensity (allostatic). The time course of changes observed in adenosine receptor mRNA levels suggests that the basal forebrain and cortical adenosine system might mediate sleepiness rather than sleep time or intensity. Citation: Kim Y; Bolortuya Y; Chen L; Basheer R; McCarley RW; Strecker RE. Decoupling of sleepiness from sleep time and intensity during chronic sleep restriction: evidence for a role of the

  17. 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

  18. The impact of sleep deprivation on sleepiness, risk factors and professional performance in medical residents.

    Science.gov (United States)

    Pikovsky, Oleg; Oron, Maly; Shiyovich, Arthur; Perry, Zvi H; Nesher, Lior

    2013-12-01

    Prolonged working hours and sleep deprivation can exert negative effects on professional performance and health. To assess the relationship between sleep deprivation, key metabolic markers, and professional performance in medical residents. We compared 35 residents working the in-house night shift with 35 senior year medical students in a cross-sectional cohort study. The Epworth Sleepiness Scale (ESS) questionnaire was administered and blood tests for complete blood count (CBC), blood chemistry panel, lipid profile and C-reactive protein (CRP) were obtained from all participants. Medical students and medical residents were comparable demographically except for age, weekly working hours, reported weight gain, and physical activity. The ESS questionnaires indicated a significantly higher and abnormal mean score and higher risk of falling asleep during five of eight daily activities among medical residents as compared with medical students. Medical residents had lower high density lipoprotein levels, a trend towards higher triglyceride levels and higher monocyte count than did medical students. CRP levels and other laboratory tests were normal and similar in both groups. Among the residents, 5 (15%) were involved in a car accident during residency, and 63% and 49% reported low professional performance and judgment levels after the night shift, respectively. Medical residency service was associated with increased sleepiness, deleterious lifestyle changes, poorer lipid profile, mild CBC changes, and reduced professional performance and judgment after working the night shift. However, no significant changes were observed in CRP or in blood chemistry panel. Larger prospective cohort studies are warranted to evaluate the dynamics in sleepiness and metabolic factors overtime.

  19. 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.

  20. 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

  1. Home exercise improves the quality of sleep and daytime sleepiness of elderlies: a randomized controlled trial.

    Science.gov (United States)

    Brandão, Glauber Sá; Gomes, Glaucia Sá Brandão Freitas; Brandão, Glaudson Sá; Callou Sampaio, Antônia A; Donner, Claudio F; Oliveira, Luis V F; Camelier, Aquiles Assunção

    2018-01-01

    Aging causes physiological changes which affect the quality of sleep. Supervised physical exercise is an important therapeutic resource to improve the sleep of the elderlies, however there is a low adherence to those type of programs, so it is necessary to implement an exercise program which is feasible and effective. The study aimed to test the hypothesis that a semi-supervised home exercise program, improves sleep quality and daytime sleepiness of elderlies of the community who present poor sleep quality. This was a randomized controlled trial study, conducted from May to September 2017, in Northeastern Brazil, with elderlies of the community aging 60 years old or older, sedentary, with lower scores or equal to 5 at the Pittsburgh Sleep Quality Index (PSQI) and without cognitive decline. From one hundred ninety-one potential participants twenty-eight refused to participate, therefore, one hundred thirty-one (mean age 68 ± 7 years), and 88% female, were randomly assigned to an intervention group - IG (home exercise and sleep hygiene, n  = 65) and a control group - CG (sleep hygiene only, n  = 66). Sleep assessment tools were used: PSQI, Epworth sleepiness scale (ESS) and clinical questionnaire of Berlin. The level of physical activity has been assessed by means of International Physical Activity Questionnaire adapted for the elderly (IPAQ) and Mini-Mental State Examination for cognitive decline. All participants were assessed before and after the 12-week intervention period and, also, the assessors were blind. The IG showed significant improvement in quality of sleep with a mean reduction of 4.9 ± 2.7 points in the overall PSQI ( p  exercise is effective in improving the quality of sleep and self-referred daytime sleepiness of sedentary elderlies of the community who presented sleep disorders. Ensaiosclinicos.gov.br process number: RBR-3cqzfy.

  2. A diagnostic dilemma: drug-induced aseptic meningitis in a 45-year-old HIV-positive man.

    LENUS (Irish Health Repository)

    Rowley, D

    2014-03-01

    We describe a case of aseptic meningitis following the administration of moxifloxacin in a 45-year-old man with human immunodeficiency virus (HIV). At presentation he was receiving tuberculosis treatment on a modified regimen following severe hepatotoxicity; this included moxifloxacin, started 8 days previously. Initial cerebrospinal fluid (CSF) analysis was grossly abnormal. Anti-viral and -bacterial treatments were started. All microbiological tests proved negative and his moxifloxacin was withheld resulting in a complete normalisation of CSF. Drug-induced aseptic meningitis is a diagnosis of exclusion and presents a serious diagnostic dilemma. The decision to withhold medication cannot be taken lightly.

  3. Drug-induced hypersensitivity syndrome caused by valproic acid as a monotherapy for epilepsy: First case report in Asian population

    Directory of Open Access Journals (Sweden)

    X.T. Wu

    2017-01-01

    Full Text Available Valproic acid (VPA is a broad-spectrum antiseizure drug used for a variety of clinical conditions, such as epilepsy and mood disorders. Drug-induced hypersensitivity syndrome (DRESS accompanied by hyponatremia, thrombocytopenia, hypoalbuminemia and elevated aminotransferase has never been reported as an adverse effect of VPA monotherapy during titration for epilepsy in Asian population. Hereby, we present the case of a 73-year-old Chinese male who suffered from DRESS and other complications two weeks after initiating VPA treatment for epilepsy. Understanding the risk associated with VPA-induced DRESS, and taking effective measures to avoid the severe side effects are necessary.

  4. Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    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.

  5. Drug-induced hypersensitivity syndrome caused by valproic acid as a monotherapy for epilepsy: First case report in Asian population.

    Science.gov (United States)

    Wu, X T; Hong, P W; Suolang, D J; Zhou, D; Stefan, H

    2017-01-01

    Valproic acid (VPA) is a broad-spectrum antiseizure drug used for a variety of clinical conditions, such as epilepsy and mood disorders. Drug-induced hypersensitivity syndrome (DRESS) accompanied by hyponatremia, thrombocytopenia, hypoalbuminemia and elevated aminotransferase has never been reported as an adverse effect of VPA monotherapy during titration for epilepsy in Asian population. Hereby, we present the case of a 73-year-old Chinese male who suffered from DRESS and other complications two weeks after initiating VPA treatment for epilepsy. Understanding the risk associated with VPA-induced DRESS, and taking effective measures to avoid the severe side effects are necessary.

  6. Accounting for partial sleep deprivation and cumulative sleepiness in the Three-Process Model of alertness regulation.

    Science.gov (United States)

    Akerstedt, Torbjörn; Ingre, Michael; Kecklund, Göran; Folkard, Simon; Axelsson, John

    2008-04-01

    Mathematical models designed to predict alertness or performance have been developed primarily as tools for evaluating work and/or sleep-wake schedules that deviate from the traditional daytime orientation. In general, these models cope well with the acute changes resulting from an abnormal sleep but have difficulties handling sleep restriction across longer periods. The reason is that the function representing recovery is too steep--usually exponentially so--and with increasing sleep loss, the steepness increases, resulting in too rapid recovery. The present study focused on refining the Three-Process Model of alertness regulation. We used an experiment with 4 h of sleep/night (nine participants) that included subjective self-ratings of sleepiness every hour. To evaluate the model at the individual subject level, a set of mixed-effect regression analyses were performed using subjective sleepiness as the dependent variable. These mixed models estimate a fixed effect (group mean) and a random effect that accounts for heterogeneity between participants in the overall level of sleepiness (i.e., a random intercept). Using this technique, a point was sought on the exponential recovery function that would explain maximum variance in subjective sleepiness by switching to a linear function. The resulting point explaining the highest amount of variance was 12.2 on the 1-21 unit scale. It was concluded that the accumulation of sleep loss effects on subjective sleepiness may be accounted for by making the recovery function linear below a certain point on the otherwise exponential function.

  7. 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.

  8. Chronotype differences in circadian rhythms of temperature, melatonin, and sleepiness as measured in a modified constant routine protocol

    Directory of Open Access Journals (Sweden)

    Leon Lack

    2009-11-01

    Full Text Available Leon Lack, Michelle Bailey, Nicole Lovato, Helen WrightSchool of Psychology, Flinders University, Adelaide, South Australia, AustraliaAbstract: Evening chronotypes typically have sleep patterns timed 2–3 hours later than morning chronotypes. Ambulatory studies have suggested that differences in the timing of underlying circadian rhythms as a cause of the sleep period differences. However, differences in endogenous circadian rhythms are best explored in laboratory protocols such as the constant routine. We used a 27-hour modified constant routine to measure the endogenous core temperature and melatonin circadian rhythms as well as subjective and objective sleepiness from hourly 15-minute sleep opportunities. Ten (8f morning type individuals were compared with 12 (8f evening types. All were young, healthy, good sleepers. The typical sleep onset, arising times, circadian phase markers for temperature and melatonin and objective sleepiness were all 2–3 hours later for the evening types than morning types. However, consistent with past studies the differences for the subjective sleepiness rhythms were much greater (5–9 hours. Therefore, the present study supports the important role of subjective alertness/sleepiness in determining the sleep period differences between morning and evening types and the possible vulnerability of evening types to delayed sleep phase disorder.Keywords: chronotype, constant routine, circadian rhythms, sleep propensity, subjective sleepiness

  9. 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.

  10. Risk of obstructive sleep apnea and excessive daytime sleepiness in hospitalized psychiatric patients

    Directory of Open Access Journals (Sweden)

    Talih FR

    2017-04-01

    Full Text Available Farid R Talih,1 Jean J Ajaltouni,1 Hani M Tamim,2 Firas H Kobeissy3 1Department of Psychiatry, 2Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Objectives: This study evaluated the risk of developing obstructive sleep apnea (OSA and excessive daytime sleepiness (EDS in hospitalized psychiatric patients at the American University of Beirut Medical Center (AUB-MC. Factors associated with OSA and EDS occurrence in this sample were also examined. Methods: The Berlin questionnaire and the Epworth sleepiness scale; which respectively evaluate OSA and EDS symptoms, were administered to individuals hospitalized at an acute psychiatric treatment unit at the AUB-MC between the dates of January 2014 and October 2016. Additional data collected included general demographics, psychiatric diagnoses, and questionnaires evaluating depression and anxiety symptoms. Statistical analyses utilizing SPSS were performed to determine the prevalence of OSA and EDS, as well as their respective associations with patient profiles. Results: Our results showed that 39.5% of participants were found to have a high risk of sleep apnea and 9.9% of the participants were found to have abnormal daytime sleepiness. The risk of developing OSA was associated with a higher body mass index (BMI (P=0.02, and depression severity (patient health questionnaire 9 score (P=0.01. Increasing severity of depressive symptoms was associated with a higher risk of sleep apnea (P=0.01. BMI (odds ratio [OR] =5.97, 95% confidence interval [CI] 1.89–18.82 and depression severity (OR =4.04, 95% CI 1.80–9.07 were also found to be predictors of OSA. The psychiatric diagnoses of the participants were not found to have a significant association with the risk of sleep apnea. Conclusion: The risk of OSA is increased among hospitalized

  11. 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 (Pworkplace as they facilitate at least some sleep during the biological night and minimize deficits associated with time-on-shift with shorter shifts. Overall, the 4 hour-on/8 hour-off roster best promoted sleep and minimized sleepiness compared to other LWSW schedules. Nevertheless, and considering the safety-critical nature of industries which employ LWSW, the limited literature needs to be greatly expanded with

  12. Use of a mail-out continuing education article to teach health professionals about drug-induced disease.

    Science.gov (United States)

    Goldman, S A

    1999-11-01

    A U.S. Food and Drug Administration (FDA)/Georgetown University Medical Center conference was the basis for "Clinical Therapeutics and the Recognition of Drug-Induced Disease," the first MEDWATCH continuing education (CE) mail-out article. Developed as a major component of FDA MEDWATCH post-marketing surveillance outreach, the article used a clinical therapeutic approach to discuss topics including adverse drug events (ADEs) pharmacology and ADE reporting. Distributed nationwide through the MEDWATCH Partners, health professionals applied for CE credit by completing a self-assessment examination. With the overall response rate slightly more than 2%, 15,260 health professionals (55% physicians and 37% pharmacists) received CE credit. Evaluation of the initial approximately two-thirds (N = 10,021) of successfully completed exams found 99% agreement that stated learning objectives were met, and the article relevant to their clinical practice; spontaneous comments/letters were also very positive. The highest percentage responding specialists were internists (28%) and psychiatrists (17%), with notable differences found among specialties for response rate versus relative article distribution (such as relatively low response rates among surgeons and radiology/radiation physics specialists). The number of health professionals receiving CE credit, coupled with examination performance and overall response, indicates that "Clinical Therapeutics and the Recognition of Drug-Induced Disease" was well received and fulfilled learning objectives. The results provide encouragement for this continuing educational approach.

  13. The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury.

    Science.gov (United States)

    Woodhead, Jeffrey L; Watkins, Paul B; Howell, Brett A; Siler, Scott Q; Shoda, Lisl K M

    2017-02-01

    Idiosyncratic drug-induced liver injury (iDILI) is a serious concern in drug development. The rarity and multifactorial nature of iDILI makes it difficult to predict and explain. Recently, human leukocyte antigen (HLA) allele associations have provided strong support for a role of an adaptive immune response in the pathogenesis of many iDILI cases; however, it is likely that an adaptive immune attack requires several preceding events. Quantitative systems pharmacology (QSP), an in silico modeling technique that leverages known physiology and the results of in vitro experiments in order to make predictions about how drugs affect biological processes, is proposed as a potentially useful tool for predicting and explaining critical events that likely precede immune-mediated iDILI, as well as the immune attack itself. DILIsym, a QSP platform for drug-induced liver injury, has demonstrated success in predicting the presence of delayed hepatocellular stress events that likely precede the iDILI cascade, and has successfully predicted hepatocellular stress likely underlying iDILI attributed to troglitazone and tolvaptan. The incorporation of a model of the adaptive immune system into DILIsym would represent and important advance. In summary, QSP methods can play a key role in the future prediction and understanding of both immune-mediated and non-immune-mediated iDILI. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  14. Drug-Induced Thrombophilic or Prothrombotic States: An Underestimated Clinical Problem That Involves Both Legal and Illegal Compounds.

    Science.gov (United States)

    Girolami, A; Cosi, E; Tasinato, V; Santarossa, C; Ferrari, S; Girolami, B

    2017-10-01

    Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases.

  15. 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.

  16. Association of excessive daytime sleepiness with migraine and headache frequency in the general population.

    Science.gov (United States)

    Stavem, Knut; Kristiansen, Håvard Anton; Kristoffersen, Espen Saxhaug; Kværner, Kari Jorunn; Russell, Michael Bjørn

    2017-12-01

    Some previous studies have postulated an association between migraine and excessive daytime sleepiness (EDS). This study evaluated the association of EDS with migraine and headache frequency in a general population, after adjusting for potential confounding variables. The study was a postal survey of a random age and gender-stratified sample of 40,000 persons aged 20 to 80 years old drawn by the National Population Register in Norway. The questionnaire included questions about migraine, headache, the Epworth sleepiness scale (ESS) and various comorbidities. EDS was defined as ESS > 10. The association of EDS and migraine/headache were analysed by bivariate and multivariable logistic regression analyses. A total of 21,177 persons responded to the ESS and were included in the analyses. The odds ratio (OR) for EDS was increased for migraineurs (1.42 (95% CI 1.31─1.54), p 179 days per year compared to those without headache in multivariable analysis. In a general population, the odds for EDS increased significantly with the headache frequency, irrespective of migraine status. EDS was not associated with reported migraine in multivariable analysis.

  17. 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 (peating at night. Not eating at night was associated with elevated hunger and a small but significant elevation in stomach upset across the night (pEating 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.

  18. 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.

  19. [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 performance. Sleep efficiency 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.

  20. Snoring intensity and excessive daytime sleepiness in subjects without obstructive sleep apnea.

    Science.gov (United States)

    Kalchiem-Dekel, Or; Westreich, Roi; Regev, Adi; Novack, Victor; Goldberg, Mordechai; Maimon, Nimrod

    2016-07-01

    Snoring and excessive daytime sleepiness (EDS) are major obstructive sleep apnea (OSA) symptoms. Snorers with apnea/hypopnea index snoring intensity and EDS defined as Epworth Sleepiness Scale (ESS) scores ≥ 11 in non-OSA subjects. Prospective cohort study. From a total of 2,225 subjects who underwent polysomnography (PSG), 307 simple snorers qualified for the study and were assessed for snoring intensity and ESS score. The correlation between PSG-based snoring intensity measurements and ESS score was evaluated. A prediction model for EDS was derived using multivariate logistic regression. Subjects with EDS tended to be male and of heavier body habitus. Although both genders exhibited similar snoring intensities, men had higher ESS scores than women. A strong linear correlation was demonstrated between the maximal snoring intensity and the ESS score. Maximal snoring sound and male gender were shown to be predictors of EDS, with odds ratios of 1.93 (95% confidence interval [CI]:1.63-2.26, P snoring intensity was associated with EDS in both men and women. A positive linear correlation was observed between snoring intensities and ESS scores. Additional studies are needed to further consolidate the evidence regarding the implications of simple snoring for public health. 2b Laryngoscope, 126:1696-1701, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  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. 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.

  3. 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 sleep, 5 or more nights per week, and 60% would like more sleep. Almost half the participants (45%) report suffering the symptoms of insomnia at least once per week, with one in 5 meeting more stringent criteria for primary insomnia. Excessive daytime sleepiness (evident in 9% of this large, predominantly 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.

  4. [Impulse control behaviors associated with antiparkinsonian medications].

    Science.gov (United States)

    Depierreux-Lahaye, F; Crémers, J; Skawiniak, E; Parmentier, E; Delvaux, V; Garraux, G

    2013-01-01

    In some patients, impulse control behaviours can be triggered by dopaminergic replacement therapy, particularly dopamine agonist drugs: hobbyism, punding (stereotyped behaviours), compulsive buying, binge eating disorder, pathological gamgling, hypersexuality, hedonistic homeostatic dysregulation syndrome ... The pathogenesis of these behaviours: is not well understood, but likely involves aberrant changes in the dopaminergic pathways that mediate motivation i.e., a dopaminergic "overdose" in meso-cortico-limbic circuits, An early diagnosis is difficult, but mandatory to prevent the occurrence of devastating familial, marital, professional, socio-economic, medical and medico-legal consequences. Their management is not yet well standardized. Patients and caregivers should be warned about impulse control behaviours before starting dopamine agonists and monitoring for such behaviours while on therapy is requested.

  5. The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: A meta-analytic review

    NARCIS (Netherlands)

    Dewald, Julia F.; Meijer, Anne M.; Oort, Frans J.; Kerkhof, Gerard A.; Bögels, Susan M.

    2010-01-01

    Insufficient sleep, poor sleep quality and sleepiness are common problems in children and adolescents being related to learning, memory and school performance. The associations between sleep quality (k=16 studies, N=13,631), sleep duration (k=17 studies, N=15,199), sleepiness (k=17, N=19,530) and

  6. The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: A meta-analytic review

    NARCIS (Netherlands)

    Dewald, J.F.; Meijer, A.M.; Oort, F.J.; Kerkhof, G.A.; Bögels, S.M.

    2010-01-01

    Insufficient sleep, poor sleep quality and sleepiness are common problems in children and adolescents being related to learning, memory and school performance. The associations between sleep quality (k = 16 studies, N = 13,631), sleep duration (k = 17 studies, N = 15,199), sleepiness (k = 17, N =

  7. 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

  8. 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

  9. MicroRNA-122: a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity.

    Science.gov (United States)

    Kia, Richard; Kelly, Lorna; Sison-Young, Rowena L C; Zhang, Fang; Pridgeon, Chris S; Heslop, James A; Metcalfe, Pete; Kitteringham, Neil R; Baxter, Melissa; Harrison, Sean; Hanley, Neil A; Burke, Zoë D; Storm, Mike P; Welham, Melanie J; Tosh, David; Küppers-Munther, Barbara; Edsbagge, Josefina; Starkey Lewis, Philip J; Bonner, Frank; Harpur, Ernie; Sidaway, James; Bowes, Joanne; Fenwick, Stephen W; Malik, Hassan; Goldring, Chris E P; Park, B Kevin

    2015-03-01

    Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http

  10. Drug-induced sleep endoscopy in the identification of obstruction sites in patients with obstructive sleep apnea: a systematic review.

    Science.gov (United States)

    Viana, Alonço da Cunha; Thuler, Luiz Claudio Santos; Araújo-Melo, Maria Helena de

    2015-01-01

    Obstructive sleep apnea syndrome has multifactorial causes. Although indications for surgery are evaluated by well-known diagnostic tests in the awake state, these do not always correlate with satisfactory surgical results. To undertake a systematic review on endoscopy during sleep, as one element of the diagnosis routine, aiming to identify upper airway obstruction sites in adult patients with OSAS. By means of electronic databases, a systematic review was performed of studies using drug-induced sleep endoscopy to identify obstruction sites in patients with OSAS. Ten articles were selected that demonstrated the importance of identifying multilevel obstruction, especially in relation to retrolingual and laryngeal collapse in OSAS. DISE is an additional method to reveal obstruction sites that have not been detected in awake patients. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Skin conductance reflects drug-induced changes in blood levels of cortisol, adrenaline and noradrenaline in dogs.

    Science.gov (United States)

    Ishibashi, Maki; Akiyoshi, Hideo; Iseri, Toshie; Ohashi, Fumihito

    2013-01-01

    To verify availability of skin conductance (SC) as an indicator for the sympathetic nervous system (SNS) activity in dogs, the changes in SC and blood levels of stress-related hormones induced by drugs were compared. SC and cortisol, adrenaline and noradrenaline levels were measured in 5 dogs on 4 occasions with or without drug-induced sedation at 7-day intervals (no treatment, intramuscular medetomidine 0.01 mg/kg, intramuscular acepromazine 0.1 mg/kg and intravenous fentanyl 0.02 mg/kg). The fentanyl treatment produced significantly higher levels of SC and plasma cortisol and adrenaline compared with the other 3 treatments. The plasma noradrenaline level also tended to be higher following the fentanyl treatment. These results indicate that SC may reflect changes in the SNS activities in dogs.

  12. Consensus statement: Management of drug-induced liver injury in HIV-positive patients treated for TB

    Directory of Open Access Journals (Sweden)

    E Jong

    2013-09-01

    Full Text Available Drug-induced liver injury (DILI in HIV/tuberculosis (TB co-infected patients is a common problem in the South African setting, and re-introduction of anti-TB drugs can be challenging for the healthcare worker. Although international guidelines on the re-introduction of TB treatment are available, the definition of DILI is not uniform, management of antiretroviral therapy (ART in HIV co-infection is not mentioned, and the guidance on management is not uniform and lacks a practical approach. In this consensus statement, we summarise important aspects of DILI and provide practical guidance for healthcare workers for different patient groups and healthcare settings on the re-introduction of anti-TB drugs and ART in HIV/TB co-infected individuals presenting with DILI.

  13. Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    International Nuclear Information System (INIS)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa; Sanz-Viedma, Salome; Garcia-Solis, David; Mir, Pablo

    2010-01-01

    To determine clinical predictors and accuracy of 123 I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and 123 I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p 123 I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by 123 I-FP-CIT SPECT imaging. (orig.)

  14. Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis; Extensive Review of Reports of Drug-Induced Etiologies, and Possible Therapeutic Modalities

    Directory of Open Access Journals (Sweden)

    Adegbenro Omotuyi John Fakoya

    2018-03-01

    Full Text Available Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles information on the details of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, the pathophysiology, therapeutic management, and largely considers the drug-induced etiologies associated with these conditions.

  15. Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during therapy for drug-induced hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Tomoo Ikari

    2017-01-01

    Full Text Available A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS caused by salazosulfapyridine. Human herpes virus 6 (HHV-6 variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA, and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.

  16. Drug-induced MR urography: the effects of furosemide and intravenous saline injection on MR urography of obstructed and non-obstructed urinary tract

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Ha; Lee, Myung Jun; Lee, Chang Joon [National Medical Center, Seoul (Korea, Republic of)

    2001-10-01

    To determine the usefulness of MR urography technique for the evaluation of urinary systems in patients with obstructed urinary tract and normal volunteers with non-obstructed urinary tract after intravenous normal saline and diuretic injection. Three normal volunteers and 12 patients with urinary tract obstruction [ureteral calculi (n=8), extraurinary mass (n=1), ureteral tumor invasion (n=3)] underwent MR urography using a 1.0T scanner and a 2D non-breath-hold heavily T2-weighted fast spin-cho sequence. These acquisition were post-processed with a maximum intensity projection (MIP) algorithm. Two acquisitions were performed, the first prior to saline solution infusion following standard MR urography procedures, and the second, within 2-3 minutes of the infusion of 250 ml saline solution followed by 20 mg of Lasix administered intravenously. For this latter, drug-induced MR urography procedures were followed. In healthy volunteer (n=3) and those experiencing partial obstruction (n=4) by a urinary stone, drug-induced MR urography provided better images of the urinary tract than did standard MR urography. In those in whom a urinary stone or tumor had caused complete obstruction (n=8), standard MR urography provided good images, as did drug-induced MR urography. In patients with a partially or non-obstructed urinary tract, drug-induced MR urography provided better anatomic and functional details of the kidney and urinary tract than did standard MR urography. In those experiencing complete obstruction of the urinary tract, however, standard or drug-induced MR urography permitted very adequate evaluation of the tract, and drug-induced MR urography was unnecessary.

  17. Daytime sleepiness in elderly Parkinson’s disease patients and treatment with the psychostimulant modafinil: A preliminary study

    Directory of Open Access Journals (Sweden)

    Johan Lökk

    2010-03-01

    Full Text Available Johan LökkInstitution of Neurobiology, Caring Sciences, and Society, Karolinska Institute, Stockholm, SwedenBackground: Patients with Parkinson’s disease (PD or Parkinsonian syndromes often report excessive daytime sleepiness (EDS. The aim of this study was to evaluate the effects of the psychostimulant modafinil on elderly, institutionalized, severely impaired PD patients with EDS.Method: A three-week open study on ten institutionalized PD patients scoring >10 points on the Epworth Sleepiness Scale (ESS with modafinil eventually on 100 mg twice a day. Patients were assessed at the start, week 1, and week 3 with ESS, Clinical Global Impression (CGI scale severity of PD and appetite.Results: Reduction of ESS score and PD severity over time were found as well as a significant increase in appetite and reduction in CGI score.Conclusion: Modafinil 100 mg twice a day was safe and modestly effective for the treatment of EDS in elderly, institutionalized PD patients. Sustaining wakefulness throughout all stages of PD is crucial for participating in life, maintaining social life, and improving quality of life.Keywords: Parkinson’s disease, daytime sleepiness, Epworth sleepiness scale, psychostimulant

  18. Does more sleep matter? Differential effects of NREM- and REM-dominant sleep on sleepiness and vigilance.

    Science.gov (United States)

    Neu, D; Mairesse, O; Newell, J; Verbanck, P; Peigneux, P; Deliens, G

    2015-05-01

    We investigated effects of NREM and REM predominant sleep periods on sleepiness and psychomotor performances measured with visual analog scales and the psychomotor vigilance task, respectively. After one week of stable sleep-wake rhythms, 18 healthy sleepers slept 3hours of early sleep and 3hours of late sleep, under polysomnographic control, spaced by two hours of sustained wakefulness between sleep periods in a within subjects split-night, sleep interruption protocol. Power spectra analysis was applied for sleep EEG recordings and sleep phase-relative power proportions were computed for six different frequency bands (delta, theta, alpha, sigma, beta and gamma). Both sleep periods presented with similar sleep duration and efficiency. As expected, phasic NREM and REM predominances were obtained for early and late sleep conditions, respectively. Albeit revealing additive effects of total sleep duration, our results showed a systematic discrepancy between psychomotor performances and sleepiness levels. In addition, sleepiness remained stable throughout sustained wakefulness during both conditions, whereas psychomotor performances even decreased after the second sleep period. Disregarding exchanges for frequency bands in NREM or stability in REM, correlations between outcome measures and EEG power proportions further evidenced directional divergence with respect to sleepiness and psychomotor performances, respectively. Showing that the functional correlation pattern changed with respect to early and late sleep condition, the relationships between EEG power and subjective or behavioral outcomes might however essentially be related to total sleep duration rather than to the phasic predominance of REM or NREM sleep. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. 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.

  20. Sleep · 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome

    OpenAIRE

    Engleman, H; Douglas, N

    2004-01-01

    Sleepiness, cognitive performance, and quality of life are overlapping aspects of daytime function that may be affected in patients with obstructive sleep apnoea/hypopnoea syndrome. The evidence is compatible with hypotheses that these deficits are reversible with treatment, particularly for patients with severe disease.

  1. 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

  2. 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

  3. Subjective sleepiness and sleep quality in adolescents are related to objective and subjective measures of school performance

    Directory of Open Access Journals (Sweden)

    Annemarie eBoschloo

    2013-02-01

    Full Text Available 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 grades, self-reported school performance, and parent-reported school performance. Sleepiness – ‘I feel sleepy during the first hours at school’ – appeared to predict both school grades and self-reported school performance. Sleep quality on the other hand – as a measure of (uninterrupted sleep and/or problems falling asleep or waking up – predicted parent-reported school performance. Self- and parent-reported school performance correlated only moderately with school grades. So it turns out that the measures used to measure either sleep or school performance impacts whether or not a relation is found. Further research on sleep and school performance should take this into account. The findings do underscore the notion that sleep in adolescence can be important for learning. They are compatible with the hypothesis that a reduced sleep quality can give rise to sleepiness in the first hours at school which results in lower school performance. This notion could have applied value in counseling adolescents and their parents in changing adolescents’ sleep behavior.

  4. 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

  5. Subjective Sleepiness and Sleep Quality in Adolescents are Related to Objective and Subjective Measures of School Performance.

    Science.gov (United States)

    Boschloo, Annemarie; Krabbendam, Lydia; Dekker, Sanne; Lee, Nikki; de Groot, Renate; Jolles, Jelle

    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 grades, self-reported school performance, and parent-reported school performance. Sleepiness - "I feel sleepy during the first hours at school" - appeared to predict both school grades and self-reported school performance. Sleep quality on the other hand - as a measure of (un)interrupted sleep and/or problems falling asleep or waking up - predicted parent-reported school performance. Self- and parent-reported school performance correlated only moderately with school grades. So it turns out that the measures used to measure either sleep or school performance impacts whether or not a relation is found. Further research on sleep and school performance should take this into account. The findings do underscore the notion that sleep in adolescence can be important for learning. They are compatible with the hypothesis that a reduced sleep quality can give rise to sleepiness in the first hours at school which results in lower school performance. This notion could have applied value in counseling adolescents and their parents in changing adolescents' sleep behavior.

  6. 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

  7. 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

  8. Prevalence, Patterns, and Predictors of Sleep Problems and Daytime Sleepiness in Young Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Langberg, Joshua M.; Molitor, Stephen J.; Oddo, Lauren E.; Eadeh, Hana-May; Dvorsky, Melissa R.; Becker, Stephen P.

    2017-01-01

    Objective: The primary objective of this study was to evaluate the prevalence of multiple types of sleep problems in young adolescents with ADHD. Method: 262 adolescents comprehensively diagnosed with ADHD and their caregivers completed well-validated measures of sleep problems and daytime sleepiness. Participants also completed measures related…

  9. Proximal tubules and podocytes are toxicity targets of bucillamine in a mouse model of drug-induced kidney injury.

    Science.gov (United States)

    Fujiwara, Yoko; Tsuchiya, Hiroyoshi; Sakai, Nobuya; Shibata, Katsushi; Fujimura, Akio; Koshimizu, Taka-aki

    2011-11-16

    Effective detection of potential nephrotoxicity is crucial for pre-clinical drug development. We evaluated a sensitive animal model for drug-induced kidney injury, which includes hemi-nephrectomy of mice. Although bucillamine and d-penicillamine are used for the treatment of rheumatoid arthritis in Japan, drug-related adverse effects on the kidney can limit their therapeutic utilities. When bucillamine (1000 or 2000 mg/kg/day) or d-penicillamine (2000 mg/kg/day) were orally administered to hemi-nephrectomised BALB/c mice, the urinary protein levels of bucillamine-treated mice, but not of those treated with d-penicillamine, the vehicle, or in bucillamine treated unnephrectomized mice, were significantly increased and remained high during the 4-week drug-loading period. Membranous glomerulonephropathy occasionally seen in bucillamine/d-penicillamine-treated arthritis patients was not reproduced in mice. Instead, our mouse model showed proximal tubular injury and podocyte foot process effacement in the bucillamine-treated kidneys. These two cell types are also the primary targets of the experimental Heymann membranous glomerulonephropathy. Gene expression profiling of the bucillamine-treated mice identified lipocalin 2 as a significantly up-regulated transcript together with cytochrome P450 CYP4a14, a group-specific component, and proprotein convertase subtilisin/kexin type 9. Moreover, large amounts of lipocalin 2 were detected in the urine of the bucillamine-treated mice, but not in the hemi-nephrectomised control mice. These results indicate that hemi-nephrectomy effectively promotes acute kidney injury by bucillamine, which is accompanied by up-regulation of the urinary biomarker lipocalin 2. Our mouse model with initial stage of kidney injury should be useful to analyse the pathogenesis of drug-induced glomerular and tubular injuries. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4

    Energy Technology Data Exchange (ETDEWEB)

    Brüning, Ansgar, E-mail: ansgar.bruening@med.uni-muenchen.de; Matsingou, Christina; Brem, German Johannes; Rahmeh, Martina; Mylonas, Ioannis

    2012-10-15

    Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulated by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.

  11. Anti-hepatotoxic and antioxidant influence of Ipomoea carnea against anti-tubercular drugs induced acute hepatopathy in experimental rodents

    Directory of Open Access Journals (Sweden)

    Ramesh Kumar Gupta

    2013-11-01

    Full Text Available Objective: To assess the hepatoprotective effect of Ipomoea carnea (I. carnea extract against antitubercular drug-induced liver toxicity in experimental animals. Methods: I. carnea extracts (125, 250 and 500 mg/kg, p.o. body weight were administered daily for 35 d in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs (isoniazid 7.5 mg/kg, rifampicin 10 mg/kg and pyrazinamide 35 mg/kg given orally as suspension for 35 d in rats. Treatment groups received I. carnea extracts along with antitubercular drugs. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatise and total bilirubin. Meanwhile, in-vivo antioxidant activities as lipid peroxidation, reduced glutathione, superoxide dismutase and catalase were measured in rat liver homogenate along with ATPase and G-6-Pase. The biochemical observations were supplemented by histopathological examination. Results: Obtained results demonstrated that treatment with I. carnea extracts significantly (P<0.05-P<0.001 and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, I. carnea extracts significantly (up to P<0.001 reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes, reduced glutathione, superoxide dismutase and catalase towards normal levels. Histopathology of the liver tissue showed that I. carnea extracts attenuated the hepatocellular necrosis, massive fatty changes and led to reduction in inflammatory cells infiltration. Conclusions: The results of this study strongly indicate the protective effect of I. carnea extracts against liver injury, which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

  12. Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

    Science.gov (United States)

    Horiuchi-Yamamoto, Yuka; Gemma, Akihiko; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Sakai, Fumikazu; Johkoh, Takeshi; Fujimoto, Kiminori; Kudoh, Shoji

    2013-08-01

    Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

  13. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    International Nuclear Information System (INIS)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa; Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E.; Guo, Lining

    2013-01-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  14. Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes.

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    Elijah R Behr

    Full Text Available Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP, treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p  =  3×10(-7, odds ratio = 2, 95% confidence intervals: 1.5-2.6. The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p  =  3×10(-9. Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs.

  15. Sensitivity and Reliability of Halothane-anaesthetized Microminipigs to Assess Risk of Drug-induced Long QT Syndrome.

    Science.gov (United States)

    Cao, Xin; Wada, Takeshi; Nakamura, Yuji; Matsukura, Suchitra; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Naito, Atsuhiko T; Sugiyama, Atsushi

    2017-12-01

    Using moxifloxacin and terfenadine, which are known to induce benign and malignant QT interval prolongation, respectively, we analysed whether halothane-anaesthetized microminipigs are an appropriate model for assessing the risk of drug-induced long QT syndrome. Moxifloxacin (0.03, 0.3 and 3 mg/kg) and terfenadine (0.03, 0.3 and 3 mg/kg) were intravenously infused over 10 min. with a pause of 20 min. to the halothane-anaesthetized microminipigs (n = 4 for each drug). Moxifloxacin decreased the heart rate, whereas it increased the blood pressure in a dose-related manner. It also prolonged the PR interval and QT/QTc in a dose-related manner without altering the QRS width. Terfenadine decreased the heart rate and blood pressure, whereas it prolonged the PR interval, QRS width and QT/QTc in a dose-related manner. Terfenadine significantly prolonged the beat-to-beat variability of QT interval reflecting its pro-arrhythmic potential, which was not observed with moxifloxacin. The peak plasma concentrations of moxifloxacin and terfenadine after doses of 3 mg/kg were 4.81 and 10.15 μg/mL, respectively, which were both 1.5 times less in microminipigs than those previously reported in dogs. These results indicate that halothane-anaesthetized microminipigs would be useful for detecting drug-induced cardiovascular responses as well as differentiating benign from malignant QT interval prolongation like dogs, although there may be some differences in pharmacokinetic profile between these animals. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. Asymmetric Drug-Induced Parkinsonism and Psychopathology: A Prospective Naturalistic Study in Long-Stay Psychiatric Patients

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    Lydia E. Pieters

    2018-02-01

    Full Text Available BackgroundDrug-induced parkinsonism (DIP is the most common movement disorder induced by antipsychotics. Although DIP is mostly symmetric, asymmetric DIP is reported in a substantial part of the patients. We investigated the frequency of motor asymmetry in DIP and its relationship to the severity of psychopathology in long-stay psychiatric patients.MethodsWe obtained data from a cohort study of 207 long-stay psychiatric patients on the frequency and risk factors of tardive dyskinesia, akathisia, tardive dystonia, and DIP. From July 2003 to May 2007 (mean follow-up, 1.1 year drug-induced movement disorders were assessed at least two times in each patient, with a frequency of persistent DIP of 56.2%. All patients who had at least one time parkinsonism in the upper/lower limb(s were included for analyses (190 patients, 79 women; mean age, 48.0 ± 12.9 years. The Unified Parkinson Disease Rating Scale motor scale was used to calculate the frequency of asymmetric parkinsonism. Multilevel mixed models were built to explore the relationship between asymmetry in parkinsonism and the severity of psychopathology, measured on the Clinical Global Impression-Schizophrenia scale severity index (CGI-SCH SI.ResultsThe frequency of asymmetric parkinsonism was 20.8%. Asymmetry in parkinsonism was associated with symptom severity on all CGI-SCH SI scales (β range, 0.37–3.74 and significantly associated with the positive symptom scale (β, 3.74; 95% CI, 0.35–7.31.ConclusionDIP is asymmetric in a substantial part of patients. Asymmetric presentation of DIP is of clinical relevance as it is related to the severity of psychopathology and may alert the clinician of more severe psychopathology. Future research is recommended to provide insight into the neuropsychopathology and clinical value of asymmetric parkinsonism for psychiatric patients.

  17. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Science.gov (United States)

    Coloma, Preciosa M; Schuemie, Martijn J; Trifirò, Gianluca; Furlong, Laura; van Mulligen, Erik; Bauer-Mehren, Anna; Avillach, Paul; Kors, Jan; Sanz, Ferran; Mestres, Jordi; Oliveira, José Luis; Boyer, Scott; Helgee, Ernst Ahlberg; Molokhia, Mariam; Matthews, Justin; Prieto-Merino, David; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam

    2013-01-01

    Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings. To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects'): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association

  18. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Directory of Open Access Journals (Sweden)

    Preciosa M Coloma

    Full Text Available Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings.To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network.Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects': azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate.Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out.A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical

  19. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

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    Deborah G Nguyen

    Full Text Available Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI. This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM. Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

  20. Design of the Anti-tuberculosis Drugs induced Adverse Reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS

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    He Ping

    2010-05-01

    Full Text Available Abstract Background More than 1 million tuberculosis (TB patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS in China every year. Adverse reactions (ADRs induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA. Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI, a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.

  1. Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4

    International Nuclear Information System (INIS)

    Brüning, Ansgar; Matsingou, Christina; Brem, German Johannes; Rahmeh, Martina; Mylonas, Ioannis

    2012-01-01

    Inhibins and activins are gonadal peptide hormones of the transforming growth factor-β super family with important functions in the reproductive system. By contrast, the recently identified inhibin βE subunit, primarily expressed in liver cells, appears to exert functions unrelated to the reproductive system. Previously shown downregulation of inhibin βE in hepatoma cells and anti-proliferative effects of ectopic inhibin βE overexpression indicated growth-regulatory effects of inhibin βE. We observed a selective re-expression of the inhibin βE subunit in HepG2 hepatoblastoma cells, MCF7 breast cancer cells, and HeLa cervical cancer cells under endoplasmic reticulum stress conditions induced by tunicamycin, thapsigargin, and nelfinavir. Analysis of XPB1 splicing and ATF4 activation revealed that inhibin βE re-expression was associated with induction of the endoplasmic reticulum stress reaction by these drugs. Transfection of an ATF4 expression plasmid specifically induced inhibin βE expression in HeLa cells and indicates inhibin βE as a hitherto unidentified target gene of ATF4, a key transcription factor of the endoplasmic reticulum stress response. Therefore, the inhibin βE subunit defines not only a new player but also a possible new marker for drug-induced endoplasmic reticulum stress. -- Highlights: ► Endoplasmic reticulum stress induces inhibin beta E expression. ► Inhibin beta E is regulated by the transcription factor ATF4. ► Inhibin beta E expression can be used as a marker for drug-induced ER stress.

  2. Discussion of causes and consequences of sleepiness among college students, 2014

    Directory of Open Access Journals (Sweden)

    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.

  3. Drug-induced gingival enlargement: biofilm control and surgical therapy with gallium-aluminum-arsenide (GaAlAs) diode laser-A 2-year follow-up.

    Science.gov (United States)

    de Oliveira Guaré, Renata; Costa, Soraya Carvalho; Baeder, Fernando; de Souza Merli, Luiz Antonio; Dos Santos, Maria Teresa Botti Rodrigues

    2010-01-01

    Drug-induced gingival enlargement has been reported in patients treated with various types of anticonvulsant drugs, and is generally associated with the presence of plaque, gingival inflammation, and a genetic predisposition. Effective treatment includes daily oral hygiene and periodic professional prophylaxis. However, in some patients, surgical removal of the gingival tissue overgrowth becomes necessary. The patient in this case report was mentally impaired and had severe drug-induced gingival enlargement. This report describes the initial protocol, the gingivectomy, and a 2-year follow-up. A diode laser was used as an effective and safe method to remove the patient's overgrown gingival tissue.

  4. Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1986-01-01

    A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different...... sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow...

  5. Excessive daytime sleepiness, nocturnal sleep duration and psychopathology among Nigerian university students

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    Celestine Okorome Mume

    2011-12-01

    Full Text Available 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 interrelationship between sleep duration, EDS and psychopathology. The objectives of this study were to determine the prevalence rates of EDS and general psychopathology among university students in Nigeria; determine the range of and mean sleep duration in the students; and determine the extent to which sleep duration and EDS predict general psychopathology in the same group of subjects. Materials and methods. Eight hundred and forty-five students at Obafemi Awolowo University, Ile-Ife, Nigeria, were recruited for the study. The subjects were required to provide information on their age, gender and the total amount of sleep per night they usually had. General psychopathology was assessed using the English language version of the 30-item General Health Questionnaire (GHQ-30. They were also evaluated for EDS using the English language version of the Epworth Sleepiness Scale (ESS. Results. Six hundred and thirty-four subjects (75.03% of the participants provided complete data. The prevalence of EDS was 11.2% and the rate of general psychopathology in the subjects 13.1%. The range of sleep duration was 2 - 9 hours with a mean of 5.1 hours (standard deviation 1.3. On a regression model with the GHQ score as the dependent variable and sleep duration and ESS as the independent variables, the correlation coefficient between EDS, sleep duration and psychopathology (R was 0.47. Conclusion. EDS and psychopathology are common in the student population studied. Nocturnal sleep duration for an average student is far less than that for an average adult. Nocturnal sleep duration and EDS acted as moderate predictors of general psychopathology among

  6. The face of sleepiness: improvement in appearance after treatment of sleep apnea.

    Science.gov (United States)

    Chervin, Ronald D; Ruzicka, Deborah L; Vahabzadeh, Arshia; Burns, Margaret C; Burns, Joseph W; Buchman, Steven R

    2013-09-15

    Anecdote but no formal evidence suggests that facial appearance improves after hypersomnolent patients with obstructive sleep apnea are treated. We investigated whether masked volunteer raters can identify post- rather than pre-treatment images as looking more alert, and whether impressions are predicted by any objective changes on highly precise 3-dimensional digital photogrammetry. Participants included 20 adults with obstructive sleep apnea on polysomnography and excessive sleepiness on Epworth Sleepiness Scales. Photogrammetry was performed before and after ≥ 2 months of adherent use of positive airway pressure. Twenty-two raters then assessed pre- and post-treatment facial images, paired side-by-side in random order. Subjects included 14 men and 6 women, with mean age 45 ± 11 (SD) years and mean baseline apnea/hypopnea index of 26 ± 21. The 22 raters twice as often identified post-treatment rather than pre-treatment images to look more alert (p = 0.0053), more youthful (p = 0.026), more attractive (p = 0.0068), and more likely to reflect the treated state (p = 0.015). Photogrammetry documented post-treatment decreases in forehead surface volume and decreased infraorbital and cheek redness, but no narrowing of the interpalpebral fissure. Decreased deep NREM sleep at baseline, and pre- to post-treatment decrements in facial redness showed promise as predictors of improved subjective ratings for alertness. Patients with obstructive sleep apnea are perceived to appear more alert, more youthful, and more attractive after adherent use of positive airway pressure. Objective changes in facial surface volume and color were identified. Post-treatment decrements in redness may inform subjective impressions of improved alertness.

  7. Indicators of sleepiness in an ambulatory EEG study of night driving.

    Science.gov (United States)

    Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Chouvarda, Ioanna; Koufogiannis, D; Bekiaris, E; Maglaveras, Nikos

    2006-01-01

    Driver sleepiness due to sleep deprivation is a causative factor in 1% to 3% of all motor vehicle crashes. In recent studies, the importance of developing driver fatigue countermeasure devices has been stressed, in order to help prevent driving accidents and errors. Although numerous physiological indicators are available to describe an individual's level of alertness, the EEG signal has been shown to be one of the most predictive and reliable, since it is a direct measure of brain activity. In the present study, multichannel EEG data that were collected from 20 sleep-deprived subjects during real environmental conditions of driving are presented for the first time. EEG data's annotation made by two independent Medical Doctors revealed an increase of slowing activity and an acute increase of the alpha waves 5-10 seconds before driving events. From the EEG data that were collected, the Relative Band Ratio (RBR) of the EEG frequency bands, the Shannon Entropy, and the Kullback-Leibler (KL) Entropy were estimated for each one second segment. The mean values of these measurements were estimated for 5 minutes periods. Analysis revealed a significant increase of alpha waves relevant band ratios (RBR), a decrease of gamma waves RBR, and a significant decrease of KL entropy when the first and the last 5-min periods were compared. A rapid decrease of both Shannon and K-L entropies was observed just before the driving events. Conclusively, EEG can assess effectively the brain activity alterations that occur a few seconds before sleeping/drowsiness events in driving, and its quantitative measurements can be used as potential sleepiness indicators for future development of driver fatigue countermeasure devices.

  8. 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.

  9. Does excessive daytime sleepiness contribute to explaining the association between obesity and ADHD symptoms?

    Science.gov (United States)

    Cortese, Samuele; Konofal, Eric; Dalla Bernardina, Bernardo; Mouren, Marie-Christine; Lecendreux, Michel

    2008-01-01

    Recent studies suggest a significant association between obesity and attention-deficit/hyperactivity disorder (ADHD). The factors underlying this newly described comorbidity are still unclear and unexplored. In the present article, we propose that excessive daytime sleepiness (EDS) contributes to explaining the association between ADHD and obesity. The background for this hypothesis comes from studies on the association between ADHD and EDS, as well as from investigations on EDS in obese individuals. Available studies suggest that ADHD behaviours are significantly associated with EDS. Moreover, increasing evidence indicates that obesity is significantly associated with EDS independently of sleep-disordered breathing (SDB) or any other sleep disorders. Given the relationship between EDS and ADHD behaviors, we hypothesize that the higher than expected rates of EDS in obese individuals contribute to explaining the association between obesity and ADHD behaviors. We further speculate on the role of the brain derived neurotrophic factor (BDNF) and other molecules such as the proinflammatory cytokines IL-6 and TNF-alpha. Our hypothesis generates potentially relevant clinical and therapeutic implications. From a clinical standpoint, it may suggest to systematically look for ADHD symptoms (including hyperactivity and impulsivity) in obese patients described as sleepy. With regard to the therapeutic implications, we suggest that wake-promoting agents with anorexigenic effect, such as mazindol, might be particularly indicated for the treatment of ADHD symptoms in obese patients, since they might address both ADHD symptoms and weight reduction. In conclusion, considering the burden that ADHD adds to obesity, we believe that further studies on the comorbidity between obesity and ADHD are necessary. Research on the role of EDS might allow advancements in this field, suggesting a more effective management and, ultimately, a better quality of life of patients with both obesity and

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Sleep patterns and school performance of Korean adolescents assessed using a Korean version of the pediatric daytime sleepiness scale

    Directory of Open Access Journals (Sweden)

    Seon kyeong Rhie

    2011-01-01

    Full Text Available Purpose: Korean adolescents have severe nighttime sleep deprivation and daytime sleepiness because of their competitive educational environment. However, daytime sleep patterns and sleepiness have never been studied using age-specific methods, such as the pediatric daytime sleepiness scale (PDSS. We surveyed the daytime sleepiness of Korean adolescents using a Korean translation of the PDSS. Methods: We distributed the 27-item questionnaire, including the PDSS and questions related to sleep pattern, sleep satisfaction, and emotional state, to 3,370 students in grades 5-12. Results: The amount of nighttime sleep decreased significantly with increasing age. During weekday nights, 5- 6th graders slept for 7.95¡?#?.05; h, 7-9th graders for 7.57¡?#?.05; h, and 10-12th graders for 5.78¡?#?.13; h. However, the total amounts of combined daytime and nighttime sleep during weekdays were somewhat greater, 8.15¡?#?.12; h for 5- 6th graders, 8.17¡?#?.20; h for 7-9th graders, and 6.87¡?#?.40; h for 10-12th graders. PDSS scores increased with age, 11.89¡?#?.56; for 5- 6th graders, 16.57¡?#?.57; for 7-9th graders, and 17.71¡?#?.24; for 10-12th graders. Higher PDSS scores were positively correlated with poor school performance and emotional instability. Conclusion: Korean teenagers sleep to an unusual extent during the day because of nighttime sleep deprivation. This negatively affects school performance and emotional stability. A Korean translation of the PDSS was effective in evaluating the severity of daytime sleepiness and assessing the emotional state and school performance of Korean teenagers.

  12. 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.

  13. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Hadi, Mackenzie; Laarakkers, Coby M. M.; Masereeuw, Rosalinde; Groothuis, Geny M. M.; Russel, Frans G. M.

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker

  14. Precision-cut mouse liver slices as an ex vivo model to study the mechanism of inflammatory stress-related idiosyncratic drug-induced liver injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Chen, Y.; Starokozhko, Viktoriia; Merema, Maja; Groothuis, Genoveva

    2012-01-01

    Idiosyncratic drug reactions (IDRs) can be defined as adverse drug reactions that occur in a small minority of the patients taking clinically-relevant doses and do not involve the known pharmacological effects of the drug. IDR related to hepatotoxicity or idiosyncratic drug-induced liver injury

  15. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

    NARCIS (Netherlands)

    Kääb, Stefan; Crawford, Dana C.; Sinner, Moritz F.; Behr, Elijah R.; Kannankeril, Prince J.; Wilde, Arthur A. M.; Bezzina, Connie R.; Schulze-Bahr, Eric; Guicheney, Pascale; Bishopric, Nanette H.; Myerburg, Robert J.; Schott, Jean-Jacques; Pfeufer, Arne; Beckmann, Britt-Maria; Martens, Eimo; Zhang, Taifang; Stallmeyer, Birgit; Zumhagen, Sven; Denjoy, Isabelle; Bardai, Abdennasser; van Gelder, Isabelle C.; Jamshidi, Yalda; Dalageorgou, Chrysoula; Marshall, Vanessa; Jeffery, Steve; Shakir, Saad; Camm, A. John; Steinbeck, Gerhard; Perz, Siegfried; Lichtner, Peter; Meitinger, Thomas; Peters, Annette; Wichmann, H.-Erich; Ingram, Christiana; Bradford, Yuki; Carter, Shannon; Norris, Kris; Ritchie, Marylyn D.; George, Alfred L.; Roden, Dan M.

    2012-01-01

    Background-Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS. Methods and Results-In a

  16. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

    NARCIS (Netherlands)

    Kaeaeb, Stefan; Crawford, Dana C.; Sinner, Moritz F.; Behr, Elijah R.; Kannankeril, Prince J.; Wilde, Arthur A. M.; Bezzina, Connie R.; Schulze-Bahr, Eric; Guicheney, Pascale; Bishopric, Nanette H.; Myerburg, Robert J.; Schott, Jean-Jacques; Pfeufer, Arne; Beckmann, Britt-Maria; Martens, Eimo; Zhang, Taifang; Stallmeyer, Birgit; Zumhagen, Sven; Denjoy, Isabelle; Bardai, Abdennasser; Van Gelder, Isabelle C.; Jamshidi, Yalda; Dalageorgou, Chrysoula; Marshall, Vanessa; Jeffery, Steve; Shakir, Saad; Camm, A. John; Steinbeck, Gerhard; Perz, Siegfried; Lichtner, Peter; Meitinger, Thomas; Peters, Annette; Wichmann, H. -Erich; Ingram, Christiana; Bradford, Yuki; Carter, Shannon; Norris, Kris; Ritchie, Marylyn D.; George, Alfred L.; Roden, Dan M.

    Background-Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS. Methods and Results-In a

  17. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  20. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Claudia V.; Oliveira, Paulo J. [CNC—Center for Neuroscience and Cell Biology, University of Coimbra (Portugal); Will, Yvonne [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States); Nadanaciva, Sashi, E-mail: sashi.nadanaciva@pfizer.com [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)

    2012-10-15

    Mitochondrial DNA (mtDNA) variations including single nucleotide polymorphisms (SNPs) have been proposed to be involved in idiosyncratic drug reactions. However, current in vitro and in vivo models lack the genetic diversity seen in the human population. Our hypothesis is that different cell strains with distinct mtDNA SNPs may have different mitochondrial bioenergetic profiles and may therefore vary in their response to drug-induced toxicity. Therefore, we used an in vitro system composed of four strains of mouse embryonic fibroblasts (MEFs) with mtDNA polymorphisms. We sequenced mtDNA from embryonic fibroblasts isolated from four mouse strains, C57BL/6J, MOLF/EiJ, CZECHII/EiJ and PERA/EiJ, with the latter two being sequenced for the first time. The bioenergetic profile of the four strains of MEFs was investigated at both passages 3 and 10. Our results showed that there were clear differences among the four strains of MEFs at both passages, with CZECHII/EiJ having a lower mitochondrial robustness when compared to C57BL/6J, followed by MOLF/EiJ and PERA/EiJ. Seven drugs known to impair mitochondrial function were tested for their effect on the ATP content of the four strains of MEFs in both glucose- and galactose-containing media. Our results showed that there were strain-dependent differences in the response to some of the drugs. We propose that this model is a useful starting point to study compounds that may cause mitochondrial off-target toxicity in early stages of drug development, thus decreasing the number of experimental animals used. -- Highlights: ► mtDNA SNPs may be linked to individual predisposition to drug-induced toxicity. ► CZECHII/EiJ and PERA/EiJ mtDNA was sequenced for the first time in this study. ► Strain-dependent mitochondrial capacity differences were measured. ► Strain-dependent differences in response to mitochondrial toxicants were observed.

  1. Daytime sleepiness and attention in city bus drivers of two capitals of Brazil

    Directory of Open Access Journals (Sweden)

    D. Brasil Santos

    2013-07-01

    Full Text Available Brazil is one of the world leaders in traffic accidents. The present article studied the excessive daytime sleepiness of public transport drivers in two Brazilian's capitals and their level of attention. A descriptive transversal study of a convenient sample was conducted. For the evaluation the following were used: anthropometric variables, a Sleep Questionnaire, Epworth Scale of Sonolency (ESS, Diffused Attention Test (TADIM, and Concentrated Attention Test (TACOM-A. 300 drivers from Brasilia and 104 from Florianopolis were evaluated. The majority of the individuals were overweight and presented somnolence. The neck circumference was smaller in Brasília, where the drivers were also more sleepy and presented worst attention on TACOM-A. The analysis of correlation was significant between attention tests and age and between BMI and ESS. Factors such as differences in work journeys as well as differences between the traffic in these two cities may be associated to our findings. We concluded that sleepiness is a common factor of risk between professional bus drivers and that was correlated with BMI, as well as the attention was correlated with age. Resumo: O Brasil é um dos líderes mundiais em acidentes de trânsito. O presente artigo estudou a sonolência diurna excessiva de motoristas de transporte público de duas capitais brasileiras, bem como seus níveis de atenção. O presente estudo foi do tipo descritivo transversal, com amostra de conveniência. Para avaliação foram utilizados: variáveis antropométricas, um Questionário de Sono, a Escala de Sonolência de Epworth (ESS, o Teste de Atenção Difusa (TADIM e o Teste de Atenção Concentrada (TACOM-A. Foram avaliados 300 motoristas das cidades de Brasília e Florianópolis. A maior parte dos indivíduos apresentava-se com sobrepeso e sonolenta. A circunferência do pescoço foi menor em Brasília, onde os motoristas também eram mais sonolentos e apresentaram pior desempenho no TACOM

  2. Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder.

    Science.gov (United States)

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

    2012-08-01

    Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00-09:00 h) was significantly shorter (3.6 ± .90 min: [M ± SEM]) in the SWD group compared with that in ANW group (6.8 ± .93 min). DLMO was significantly correlated with insomnia severity (r = -.68; p vs. 180 lux [M ± SD], respectively z = -1.7; p individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule.

  3. Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

    Science.gov (United States)

    Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

    2017-01-01

    Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from t