WorldWideScience

Sample records for antiparkinsonian drug-induced sleepiness

  1. Antipsychotics dosage and antiparkinsonian prescriptions

    Directory of Open Access Journals (Sweden)

    Gasquet Isabelle

    2007-09-01

    Full Text Available Abstract Background To study the link between the dosage of several antipsychotics and the prescription of antiparkinsonians in an observational study. Methods In the context of a national naturalistic prospective observational study, a database containing all the prescriptions from 100 French psychiatrists during the year 2002 was analysed. The inclusion criteria were a diagnosis of schizophrenia or schizoaffective disorder and age over 18. The mean dosage of antipsychotics with and without antiparkinsonians was compared. Since there were multiple prescriptions for a given subject, generalised mixed linear models were also used to study the link between antiparkinsonian prescription and antipsychotic dosage. Results antiparkinsonians were prescribed to 32,9% of the patients. Two groups of antipsychotics were observed relating to differences in dosage when an antiparkinsonian was co prescribed or not : a first group, where the mean dosage was higher with antiparkinsonians (risperidone, amisulpride and haloperidol and a second group (clozapine, olanzapine, in which antiparkinsonian co prescription was not related to the dosage of antipsychotics. Conclusion As a conclusion, it can be said that it is important to consider the dosage and the type of antipsychotic in the treatment of patients suffering of schizophrenia, because neurological side effects are frequent and can impair quality of life. Moreover the prescription of antiparkinsonians can lead to different side effects such anticholinergic effects.

  2. 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

  3. Excessive Daytime Sleepiness

    OpenAIRE

    Yavuz Selvi; Ali Kandeger; Ayca Asena Sayin

    2016-01-01

    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 ...

  4. Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine.

    Science.gov (United States)

    Zivin, M; Sprah, L; Sket, D

    1998-05-22

    The ergoline derivative, LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylerg oline), has been proposed as a potential atypical antipsychotic drug with antagonistic actions at dopamine D2 and serotonin 5-HT2 and 5-HT1A receptors (Krisch et al., 1994, 1996). LEK-8829 also induces contralateral turning in rats with 6-hydroxydopamine-induced unilateral lesion of dopamine nigrostriatal neurons. Turning is blocked by SCH-23390 (R(+)-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine), a dopamine D1 receptor antagonist. It has been suggested that LEK-8829 could have beneficial effects in parkinsonian patients suffering from psychotic episodes induced as a side-effect of antiparkinsonian treatment with dopamine D2 receptor agonists. Therefore, we now investigated the interaction of LEK-8829 with the dopamine D2 receptor agonist bromocriptine (2-bromo-alpha-ergokryptine) in 6-hydroxydopamine-lesioned rats. Treatment with either LEK-8829 (3 mg kg(-1)) or bromocriptine (3 mg kg(-1)) induced a vigorous contralateral turning response. The cumulated number of turns induced by the treatment with both drugs combined was not significantly different from the cumulated number of turns induced by single-drug treatment. The pretreatment with SCH-23390 (1 mg kg(-1)) did not have a significant effect on the bromocriptine-induced turning but significantly decreased the turning observed after the combined LEK-8829/bromocriptine treatment. We conclude that in the 6-hydroxydopamine model, the turning behaviour mediated by the LEK-8829/bromocriptine combination may be the result of opposing activity of both drugs at dopamine D2 receptors with concomitant stimulation of dopamine D1 receptors by LEK-8829. Therefore, LEK-8829 may have a potential for the therapy of parkinsonism complicated by dopamine D2 receptor agonist drug-induced psychosis.

  5. 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 ...

  6. Drug-induced hepatitis

    Science.gov (United States)

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  7. Drug-induced catatonia.

    Science.gov (United States)

    Duggal, Harpreet S; Singh, Ira

    2005-09-01

    Catatonia is a heterogeneous syndrome that varies in etiology, presentation, course and sequelae. Initially conceptualized as a subtype of schizophrenia, catatonia is now recognized to occur not only with other psychiatric conditions but also with medical conditions and drug-induced and toxic states. While drug-induced catatonia is now a recognized entity, most studies club it with catatonia due to general medical conditions or organic catatonia, thus precluding any meaningful interpretation of such cases. The literature on drug-induced catatonia mostly draws from scattered case reports. This article attempts to review the available literature in this realm and integrate the information in an attempt to explore the epidemiology, etiology, mechanism and treatment of drug-induced catatonia.

  8. 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.

  9. Drug-induced diarrhoea.

    Science.gov (United States)

    Chassany, O; Michaux, A; Bergmann, J F

    2000-01-01

    Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several

  10. Drug-induced gynecomastia.

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    Eckman, Ari; Dobs, Adrian

    2008-11-01

    Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

  11. Drug-induced lupus.

    Science.gov (United States)

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  12. Dietary influences on the antiparkinsonian response to levodopa.

    Science.gov (United States)

    Juncos, J L; Fabbrini, G; Mouradian, M M; Serrati, C; Chase, T N

    1987-10-01

    The ability of dietary factors to modify the response to levodopa was evaluated in six patients with idiopathic Parkinson's disease who manifested fluctuations in motor performance. The single oral administration of a high-protein formula substantially elevated plasma large neutral amino acid levels, and prematurely terminated the antiparkinsonian response to levodopa/carbidopa. In contrast, during oral or intravenous administration of levodopa, the ingestion of diets meeting the recommended daily allowance (RDA) for protein had no significant effect on plasma levodopa or large neutral amino acid levels or variance, nor on parkinsonian scores or variance. The results suggest that while protein intake in excess of the RDA can diminish the antiparkinsonian response to orally administered levodopa/carbidopa in patients with advanced disease, diets adhering to RDA protein guidelines have no clinically appreciable effect.

  13. Influence of benzodiazepines on antiparkinsonian drug treatment in levodopa users

    OpenAIRE

    2002-01-01

    OBJECTIVES: Animal studies showed that benzodiazepines decrease the concentration of dopamine in the striatum. Benzodiazepines may therefore affect the treatment of Parkinson's disease. This study determined whether start of a benzodiazepine in patients on levodopa was followed by a faster increase of antiparkinsonian drug treatment. METHODS: Data came from the PHARMO database, which includes information on drug dispensing for all residents of six Dutch cities. Selected were all patients aged...

  14. 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.

  15. Drug-induced lupus erythematosus

    Directory of Open Access Journals (Sweden)

    M. Carrabba

    2011-09-01

    Full Text Available Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with the idiopathic systemic lupus erythematosus (SLE. The list of medications implicated as etiologic agents in drug-induced lupus continues to grow. The terms used for this condition are lupus-like syndrome, drug-induced lupus erythematosus (DILE and drug related lupus. More than 80 drugs have been associated with DILE. The first case of DILE was reported in 1945 and associated with sulfadiazin. In 1953 it was reported that DILE was related to the use of hydralazine. Drugs responsible for the development of DILE can divided into three groups, but the list of these drugs is quite long because new drugs are included yearly in the list. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug.

  16. Drug-Induced Metabolic Acidosis.

    Science.gov (United States)

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    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.

  17. Drug-induced renal disease.

    Science.gov (United States)

    Curtis, J R

    1979-11-01

    The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

  18. Drug-induced cutaneous vasculitides.

    Science.gov (United States)

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Quintarelli, L; Volpi, W; Fabbri, P; Caproni, M

    2015-04-01

    Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

  19. Drug-Induced Sleep Endoscopy.

    Science.gov (United States)

    Charakorn, Natamon; Kezirian, Eric J

    2016-12-01

    Drug-induced sleep endoscopy (DISE) is an upper airway evaluation technique in which fiberoptic examination is performed under conditions of unconscious sedation. Unique information obtained from this 3-dimensional examination of the airway potentially provides additive benefits to other evaluation methods to guide treatment selection. This article presents recommendations regarding DISE technique and the VOTE Classification system for reporting DISE findings and reviews the evidence concerning DISE test characteristics and the association between DISE findings and treatment outcomes.

  20. Armodafinil for excessive daytime sleepiness.

    Science.gov (United States)

    Nishino, Seiji; Okuro, Masashi

    2008-06-01

    Armodafinil is the (R)-enantiomer of the wakepromoting compound modafinil (racemic), with a considerably longer half-life of 10-15 hours. Armodafinil (developed by Cephalon, Frazer, PA, USA) was approved in June 2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea syndrome and shift work disorder, and the indications are the same as those for modafinil. Like modafinil, the mechanisms of action of armodafinil are not fully characterized and are under debate. Clinical trials in these sleep disorders demonstrated an enhanced efficacy for wake promotion (wake sustained for a longer time period using doses lower than those of modafinil). The safety profile is consistent with that of modafinil, and armodafinil is well tolerated by the patients. Like modafinil, armodafinil is classified as a non-narcotic Schedule IV compound. Many patients with excessive sleepiness may prefer the longer duration of effect and may have better compliance (with low doses) with armodafinil. The commercial challenge to armodafinil may come from generic modafinil, which may become available in 2012, as well as from classical amphetamine and amphetamine-like compounds (for the treatment of narcolepsy).

  1. 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...... during the last 2 years of the decade. Based on consumption data, the incidence of hepatic injury due to sulindac was estimated to be 18-fold higher than that due to ibuprofen. Paracetamol was reported to induce acute cytotoxic as well as cholestatic reactions in non-alcoholic subjects taking therapeutic...

  2. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

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

  3. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  4. 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.

  5. 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.

  6. Drug-induced liver injury

    DEFF Research Database (Denmark)

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

    2017-01-01

    biochemical findings included bilirubin elevated to above 3.2 × ULN, ALT elevated to above 9 × ULN in 86%, INR above 1.4 in 70%. Twenty two patients needed treatment in the liver intensive care unit. Fifteen patients developed acute liver failure with a severe outcome. Six patients were liver transplanted......OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors...... and outcome. RESULTS: Of 43 patients, 25 (58%) were female with a mean age of 54 years. The two most frequent causes of DILI were Disulfiram (30%) and antibiotics (19%). The most common symptoms were jaundice, nausea, fatigue and gastrointestinal discomfort. At the time of admission, the most frequent...

  7. Drug-induced sexual dysfunction.

    Science.gov (United States)

    Aldridge, S A

    1982-01-01

    Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

  8. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

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

  9. 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.

  10. Drug Induced Hearing Loss: What Is Ototoxicity?

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Drug-Induced Hearing Loss What Is Ototoxicity? Past Issues / Spring 2016 Table ... of patients taking these drugs." "Antibiotics Caused My Hearing Loss..." Gulab Lalwani Photo Courtesy of: Gulab Lalwani When ...

  11. Antiparkinsonian treatment for depression in Parkinson’s disease:Are selective serotonin reuptake inhibitors recommended?

    Institute of Scientific and Technical Information of China (English)

    Philippe De Deurwaerdre; Yuqiang Ding

    2016-01-01

    Depression is a frequent comorbid syndrome in Parkinson’s disease. It is a difficult symptom to manage, as patients continuously receive antiparkinsonian medication and may also have to be treated for the amelioration of the side-effects of antiparkinsonian therapy. The first-line treatment for depression in Parkinson’s disease is the use of selective serotonin reuptake inhibitors (SSRIs). The clinical efficacy of these medications in patients with Parkinson’s disease is questionable. In fact, based on their mechanism of action, which requires at least a functional serotonergic system, it is predicted that SSRIs will have lower efficacy in patients with Parkinson’s disease. Here, we consider the mechanism of action of SSRIs in the context of Parkinson’s disease by investigating the fall in the levels of serotonergic markers and the inhibitory outcomes of antiparkinsonian treatment on serotonergic nerve activity. Because certain classes of antidepressant drugs are widely available, it is necessary to perform translational research to address different strategies used to manage depression in Parkinson’s disease.

  12. 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.

  13. Multilevel Intervention Mapping with sleepiness in focus

    NARCIS (Netherlands)

    Hof, T.; Wilschut, E.S.

    2011-01-01

    This report provides an overview of methods to prevent drowsy driving of drivers (Wilschut et al., 2009). Several preventive approaches were discussed such as the use of questionnaires, campaigns and fatigue management plans. A search for law enforcement instruments to prevent sleepiness at the whee

  14. Factors influencing excessive daytime sleepiness in adolescents

    Directory of Open Access Journals (Sweden)

    Thiago de Souza Vilela

    2016-04-01

    Full Text Available Abstract Objective: Sleep deprivation in adolescents has lately become a health issue that tends to increase with higher stress prevalence, extenuating routines, and new technological devices that impair adolescents' bedtime. Therefore, this study aimed to assess the excessive sleepiness frequency and the factors that might be associated to it in this population. Methods: The cross-sectional study analyzed 531 adolescents aged 10–18 years old from two private schools and one public school. Five questionnaires were applied: the Cleveland Adolescent Sleepiness Questionnaire; the Sleep Disturbance Scale for Children; the Brazilian Economic Classification Criteria; the General Health and Sexual Maturation Questionnaire; and the Physical Activity Questionnaire. The statistical analyses were based on comparisons between schools and sleepiness and non-sleepiness groups, using linear correlation and logistic regression. Results: Sleep deprivation was present in 39% of the adolescents; sleep deficit was higher in private school adolescents (p < 0.001, and there was a positive correlation between age and sleep deficit (p < 0.001; r = 0.337. Logistic regression showed that older age (p = 0.002; PR: 1.21 [CI: 1.07–1.36] and higher score level for sleep hyperhidrosis in the sleep disturbance scale (p = 0.02; PR: 1.16 [CI: 1.02–1.32] were risk factors for worse degree of sleepiness. Conclusions: Sleep deficit appears to be a reality among adolescents; the results suggest a higher prevalence in students from private schools. Sleep deprivation is associated with older age in adolescents and possible presence of sleep disorders, such as sleep hyperhidrosis.

  15. Pharmacogenetics of drug-induced arrhythmias

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...... were screened for 10 missense mutations in 5 genes associated with the congenital long-QT (LQT) syndrome (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2). RESULTS: We identified 45 eligible cases, 29 GPs could be contacted of which seven were willing to participate. Four cases and five matched controls could...

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

    Directory of Open Access Journals (Sweden)

    Ashleigh J Filtness

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

  17. Drug-induced hyperthermia in Huntington's disease.

    NARCIS (Netherlands)

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

    2004-01-01

    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 m

  18. Treatment of drug-induced seizures.

    Science.gov (United States)

    Chen, Hsien-Yi; Albertson, Timothy E; Olson, Kent R

    2016-03-01

    Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established.

  19. Drug-induced arrhythmias, quantifying the problem

    NARCIS (Netherlands)

    Bruin, M.L. de

    2004-01-01

    Cardiac arrhythmias as an adverse reaction to the use of non-antiarrhythmic drugs have attracted much attention during recent years. It has become the single most common reason for regulatory action regarding the marketing of drugs. Although drug-induced arrhythmias are very rare (approximately 1 pe

  20. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael;

    2010-01-01

    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....

  1. Armodafinil in the treatment of excessive sleepiness

    OpenAIRE

    Rosenberg, Russell

    2010-01-01

    Russell Rosenberg1, Richard Bogan21NeuroTrials Research, Atlanta, Georgia, USA; 2SleepMed of South Carolina, Columbia, South Carolina, USAAbstract: Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or narcolepsy. ES poses significant health and safety concerns in patients. Numerous interventions are available to treat the underlying causes of ES and ES itself, including behavioral...

  2. Armodafinil in the treatment of excessive sleepiness

    OpenAIRE

    Rosenberg, Russell; Bogan, Richard

    2010-01-01

    Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/ wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or narcolepsy. ES poses significant health and safety concerns in patients. Numerous interventions are available to treat the underlying causes of ES and ES itself, including behavioral measures, mechanical devices, and pharmacologic agents. This review explores the evidence supporting the use of armodafinil to treat ES associated...

  3. Mechanistic Review of Drug-Induced Steatohepatitis

    Science.gov (United States)

    Schumacher, Justin; Guo, Grace

    2015-01-01

    Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A. It has been found that the majority of compounds that induce steatohepatitis have cationic amphiphilic structures; a lipophilic ring structure with a side chain containing a cationic secondary or tertiary amine. Within the last decade, the ability of many chemotherapeutics to cause steatohepatitis has become more evident coining the term chemotherapy-associated steatohepatitis (CASH). The mechanisms behind drug-induced steatohepatitis are discussed with a focus on cationic amphiphilic drugs and chemotherapeutic agents. PMID:26344000

  4. 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.

  5. Causes and consequences of sleepiness among college students

    OpenAIRE

    Hershner SD; Chervin RD

    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 ...

  6. 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.

  7. Drug induced lung disease - amiodarone in focus

    Directory of Open Access Journals (Sweden)

    Vasić Nada R.

    2014-01-01

    Full Text Available More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%.

  8. Determinants of sleepiness at work among railway control workers.

    Science.gov (United States)

    Cotrim, Teresa; Carvalhais, José; Neto, Catarina; Teles, Júlia; Noriega, Paulo; Rebelo, Francisco

    2017-01-01

    In the last two decades the control of the Portuguese railway network has become much more centralized in three centres, there integrating the functions of route flow management, electrical control and signalling. This study aimed to investigate the influence of work and individual determinants in sleepiness among railway control workers, namely socio-demographic factors, work ability, psychosocial factors, shiftwork characteristics, fatigue perception, and sleep. Sleepiness by shift was associated with quality of sleep, job satisfaction, fatigue perception, quantitative demands, and age. The results indicate a high prevalence of sleepiness during the night shift and show the relevance of the quality of sleep as a predictor in the three models of sleepiness for morning, afternoon and night shifts. This study, done at the major Portuguese railway control centre, alerted managers to the importance of schedule planning as well as sleepiness prevention plans and makes these results a reference for future research.

  9. Are insomniacs sleepy during the day? A pupillometric assessment.

    Science.gov (United States)

    Lichstein, K L; Johnson, R S; Sen Gupta, S; O'Laughlin, D L; Dykstra, T A

    1992-05-01

    A biodevelopmental model of insomnia is articulated specifying coordinated nighttime (disturbed sleep pattern) and daytime (no excessive daytime sleepiness) characteristics defining an insomnoid classification in at-risk groups: short sleepers and older adults. Pupillometry is proposed as a useful means of discriminating degree of daytime sleepiness to aid in the differential diagnosis of insomnia and insomnoid states, and the present study tested the discriminative validity of this approach. Noninsomniac (n = 34) and insomniac (n = 29) college students submitted to four 10 min pupillometry sessions tracking daytime sleepiness from morning arising to bedtime. Pupil diameter proved to be an able discriminator of these two groups though substantial overlap of the two distributions was also noted. The results supported the sensitivity of pupillometry in detecting daytime sleepiness, but yielded alternative interpretations. We observed statistical differentiation in insomniac and noninsomniac daytime sleepiness, but substantial, functional overlap between these groups. Assessment and treatment implications arising from the biodevelopmental model were hypothesized.

  10. 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

  11. [DRUGS-INDUCED URTICARIA AND ANGIOEDEMA].

    Science.gov (United States)

    Braire-Bourrel, Marion; Augey, Frédéric; Doutre, Marie-Sylvie

    2015-09-01

    Drug-induced urticaria and/or angioedema is a frequent issue encountered in family medicine. A specific collection of the anamnesis and of the general context is very important to appreciate the involved mechanism, allergic or not, and potential cofactors. If in doubt about an allergic mechanism, tests will be conducted, mostly under a hospital setting. Bradykinin-mediated angioedema, so much rare than histamine-mediated one, has to be known, because it is potentially lethal. It is often iatrogenic (ACE inhibitors especially). At the end of the allergology work-up, a course of action is proposed to the patient and his family practitioner as far as the rechallenge of the drug is concerned, In case of non-allergic urticaria, much more frequent than allergy, taking the drug is possible with a premedication with antihistamines.

  12. Pathogenesis of drug induced acneform eruptions

    Directory of Open Access Journals (Sweden)

    Lobo Audrey

    1992-01-01

    Full Text Available To determine the pathogenesis of drug induced acneform eruption (DAE, 44 patients were evaluated clinically and representative samples histologically. INAH and corticosteroids were the main offenders in 38.6 percent and 36.4 percent patients respectively. Chloroquin precipitated lesions in 9.1 percent of the patients. There were significant differences in the duration of drug-intake before onset, morphology and severity of lesions. Histological differences with different drugs were also noted. Based on clinical and histological findings, pathogenesis of lesions caused by different drugs could be suggested. Keratinization of follicular epithelium was the main effect with corticosteroids and INAH. Suppuration of follicular epithelium was an additional early event with corticosteroids. Type III allergic reaction was responsible for iodine lesions and delayed hypersensitivity for chlorpromazine and chloroquine induced lesions.

  13. Drug-induced cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  14. The discovery of drug-induced illness.

    Science.gov (United States)

    Jick, H

    1977-03-01

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

  15. 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.

  16. Modification of the Epworth Sleepiness Scale in Central China

    OpenAIRE

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

    2011-01-01

    Purpose The well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China. Methods A Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was adm...

  17. The Romantic Prototype of The Legend of Sleepy Hollow

    Institute of Scientific and Technical Information of China (English)

    冯育军; 王艳

    2016-01-01

    "The Legend of Sleepy Hollow" is a short story of speculative fiction by American author Washington Irving, con-tained in his collection of 34 essays and short stories entitled The Sketch Book of Geoffrey Crayon, Gent. Written while Irving was living abroad in Birmingham, England,"The Legend of Sleepy Hollow"was first published in 1820. Along with Irving's com-panion piece"Rip Van Winkle","The Legend of Sleepy Hollow"is among the earliest examples of American fiction with endur-ing popularity, especially during the Halloween season.

  18. Observer rated sleepiness and real road driving: an explorative study.

    Directory of Open Access Journals (Sweden)

    Anna Anund

    Full Text Available The aim of the present study was to explore if observer rated sleepiness (ORS is a feasible method for quantification of driver sleepiness in field studies. Two measures of ORS were used: (1 one for behavioural signs based on facial expression, body gestures and body movements labelled B-ORS, and (2 one based on driving performance e.g. if swerving and other indicators of impaired driving occurs, labelled D-ORS. A limited number of observers sitting in the back of an experimental vehicle on a motorway about 2 hours repeatedly 3 times per day (before lunch, after lunch, at night observed 24 participant's sleepiness level with help of the two observer scales. At the same time the participant reported subjective sleepiness (KSS, EOG was recorded (for calculation of blink duration and several driving measure were taken and synchronized with the reporting. Based on mixed model Anova and correlation analysis the result showed that observer ratings of sleepiness based on drivers' impaired performance and behavioural signs are sensitive to extend the general pattern of time awake, circadian phase and time of driving. The detailed analysis of the subjective sleepiness and ORS showed weak correspondence on an individual level. Only 16% of the changes in KSS were predicted by the observer. The correlation between the observer ratings based on performance (D-ORS and behavioural signs (B-ORS are high (r = .588, and the B-ORS shows a moderately strong association (r = .360 with blink duration. Both ORS measures show an association (r>0.45 with KSS, whereas the association with driving performance is weak. The results show that the ORS-method detects the expected general variations in sleepy driving in field studies, however, sudden changes in driver sleepiness on a detailed level as 5 minutes is usually not detected; this holds true both when taking into account driving behaviour or driver behavioural signs.

  19. Armodafinil in the treatment of excessive sleepiness.

    Science.gov (United States)

    Rosenberg, Russell; Bogan, Richard

    2010-01-01

    Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/ wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or narcolepsy. ES poses significant health and safety concerns in patients. Numerous interventions are available to treat the underlying causes of ES and ES itself, including behavioral measures, mechanical devices, and pharmacologic agents. This review explores the evidence supporting the use of armodafinil to treat ES associated with OSA, SWD, and narcolepsy. Armodafinil is an oral non-amphetamine wake-promoting agent, the R-isomer of racemic modafinil. Armodafinil and modafinil share many clinical and pharmacologic properties and are distinct from central nervous system stimulants; however, the mechanisms of action of modafinil and armodafinil are poorly characterized. Compared with modafinil, the wake-promoting effects of armodafinil persist later in the day. It is for this reason that armodafinil may be a particularly appropriate therapy for patients with persistent ES due to OSA, SWD, or narcolepsy.

  20. 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.

  1. Inhibition of West Nile virus multiplication in cell culture by anti-parkinsonian drugs

    Directory of Open Access Journals (Sweden)

    Ana Belen Blazquez

    2016-03-01

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus maintained in a transmission cycle between mosquitoes and birds, but it can also infect other vertebrates, including humans, in which it can cause neuroinvasive diseases. To date, no licensed vaccine or therapy for human use against this pathogen is yet available. A recent approach to search for new antiviral agent candidates is the assessment of long-used drugs commonly administered by clinicians to treat human disorders in drug antiviral development. In this regard, as patients with West Nile encephalitis frequently develop symptoms and features of parkinsonism, and cellular factors altered in parkinsonism, such as alpha-synuclein, have been shown to play a role on WNV infection, we have assessed the effect of four drugs (L-dopa, Selegiline, Isatin and Amantadine, that are used as therapy for Parkinson´s disease in the inhibition of WNV multiplication. L-dopa, Isatin, and Amantadine treatments significantly reduced the production of infectious virus in all cell types tested, but only Amantadine reduced viral RNA levels. These results point to antiparkinsonian drugs as possible therapeutic candidates for the development of antiviral strategies against WNV infection.

  2. [Risk factors and subjective symptoms of drug-induced leucopenia].

    Science.gov (United States)

    Hayashi, Kyoko; Ohtsu, Fumiko; Yano, Reiko; Sakakibara, Jinsaku; Goto, Nobuyuki

    2011-01-01

    The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

  3. Melatonin modulates drug-induced acute porphyria

    Directory of Open Access Journals (Sweden)

    Sandra M. Lelli

    2016-01-01

    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.

  4. Drug-induced parkinsonism: diagnosis and management

    Directory of Open Access Journals (Sweden)

    Blanchet PJ

    2016-09-01

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

  5. Sleep disorders, sleepiness and traffic safety: a public health menace

    Directory of Open Access Journals (Sweden)

    S.R. Pandi-Perumal

    2006-07-01

    Full Text Available Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

  6. 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

  7. Drug-induced angioedema without urticaria.

    Science.gov (United States)

    Agostoni, A; Cicardi, M

    2001-01-01

    probability that such an agent could be the cause. The most important action to take in a patient with suspected drug-induced angioedema is to discontinue the pharmacological agent. Epinephrine (adrenaline), diphenydramine and intravenous methylprednisolone have been proposed for the medical management of airway obstruction, but so far no controlled studies have demonstrated their efficacy. If the acute airway obstruction leads to life-threatening respiratory compromise an emergency cricothyroidotomy must be performed.

  8. An update on risk factors for drug-induced arrhythmias.

    Science.gov (United States)

    Vlachos, Konstantinos; Georgopoulos, Stamatis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ''effect amplifiers'' which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, Tpeak-Tend/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias.

  9. 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 ...

  10. Phenotypes and Pathology of Drug-Induced Liver Disease.

    Science.gov (United States)

    Goodman, Zachary D

    2017-02-01

    Drug hepatotoxicity can simulate nearly any clinical syndrome or pathologic lesion that may occur in the liver, so clinical and histopathologic diagnosis of drug-induced liver injury may be difficult. Nevertheless, most drugs that are known to idiosyncratic liver injury tend to cause patterns of injury that produce characteristic phenotypes. Recognition of these patterns or phenotypes in liver biopsy material is helpful in evaluation of clinical cases of suspected drug-induced liver injury.

  11. Acute and subacute drug-induced movement disorders.

    Science.gov (United States)

    Burkhard, Pierre R

    2014-01-01

    Many pharmacological agents may induce a variety of movement disorders, including dystonia, tremor, parkinsonism, myoclonus and dyskinesia, with an acute, subacute or more chronic time course. Motor symptoms may be isolated or part of a more extensive cerebral or systemic condition, such as the neuroleptic malignant syndrome or the serotonin syndrome. Drug-induced movement disorders share a number of features that should make them easy to identify, including a clear temporal relationship between medication initiation and symptom onset, a dose-effect, and, with the exception of tardive syndromes, complete resolution after discontinuation of the offending agent. Diagnosis relies on a thorough medication history. Medications commonly involved include dopamine receptor blockers, antidepressants and anti-epileptics, among many others. Mechanisms underlying drug-induced movement disorders involve blockade, facilitation or imbalance of dopamine, serotonin, noradrenaline and cholinergic neurotransmission in the basal ganglia. The present review focuses on drug-induced movement disorders that typically develop as an acute (hours to days) or subacute (days to weeks) event, including acute dystonic reactions, akathisia, drug-induced parkinsonism, neuroleptic malignant syndrome, serotonin syndrome, parkinsonism-hyperpyrexia syndrome, drug-induced tremor, drug-induced hyperkinesias and movement disorders associated with the use of recreational drugs.

  12. Evaluation of in-car systems that prevent sleepiness

    NARCIS (Netherlands)

    Wilschut, E.S.; Caljouw, C.J.; Valk, P.J.L.

    2011-01-01

    This report provides an overview of methods to prevent drowsy driving of drivers (Wilschut et al., 2009). Several preventive approaches were discussed such as the use of questionnaires, campaigns and fatigue management plans. A search for law enforcement instruments to prevent sleepiness at the whee

  13. 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

  14. Contemporary review of drug-induced pancreatitis: A different perspective

    Institute of Scientific and Technical Information of China (English)

    Whitney; Y; Hung; Odaliz; Abreu; Lanfranco

    2014-01-01

    Although gallstone and alcohol use have been consid-ered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are as-sociated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pan-creatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal rela-tionship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classifi-cation systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continu-ously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifacto-rial nature of acute pancreatitis call for a different ap-proach. In this article, we review the potential mecha-nisms of drug induced acute pancreatitis and providethe perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pan-creatitis with limited data.

  15. Residual Daytime Sleepiness in Obstructive Sleep Apnea After Continuous Positive Airway Pressure Optimization: Causes and Management.

    Science.gov (United States)

    Chapman, Julia L; Serinel, Yasmina; Marshall, Nathaniel S; Grunstein, Ronald R

    2016-09-01

    Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA), but it is also common in the general population. When sleepiness remains after continuous positive airway pressure (CPAP) treatment of OSA, comorbid conditions or permanent brain injury before CPAP therapy may be the cause of the residual sleepiness. There is currently no broad approach to treating residual EDS in patients with OSA. Individual assessment must be made of comorbid conditions and medications, and of lifestyle factors that may be contributing to the sleepiness. Modafinil and armodafinil are the only pharmacologic agents indicated for residual sleepiness in these patients.

  16. Sleepiness, driving, and motor vehicle accidents: A questionnaire-based survey.

    Science.gov (United States)

    Zwahlen, Daniel; Jackowski, Christian; Pfäffli, Matthias

    2016-11-01

    In Switzerland, the prevalence of an excessive daytime sleepiness (EDS) in drivers undergoing a driving capacity assessment is currently not known. In this study, private and professional drivers were evaluated by means of a paper-based questionnaire, including Epworth Sleepiness Scale, Berlin Questionnaire, and additional questions to sleepiness-related accidents, near-miss accidents, health issues, and demographic data. Of the 435 distributed questionnaires, 128 completed were returned. The response rate was 29%. The mean age of the investigated drivers was 42.5 years (20-85 years). According to the Epworth Sleepiness Scale, 9% of the participants are likely to suffer from excessive daytime sleepiness. An equal percentage has a high risk for obstructive sleep apnea syndrome based on the Berlin Questionnaire. 16% admitted an involuntary nodding off while driving a motor vehicle. This subset of the participants scored statistically significant higher on the Epworth Sleepiness Scale (p = 0.036). 8% of the participants already suffered an accident because of being sleepy while driving. An equal number experienced a sleepiness-related near-miss accident on the road. The study shows that a medical workup of excessive daytime sleepiness is highly recommended in each driver undergoing a driving capacity assessment. Routine application of easily available and time-saving assessment tools such as the Epworth Sleepiness Scale questionnaire could prevent accidents in a simple way. The applicability of the Berlin Questionnaire to screen suspected fatal sleepiness-related motor vehicle accidents is discussed.

  17. Visual contrast sensitivity in drug-induced Parkinsonism.

    Science.gov (United States)

    Bulens, C; Meerwaldt, J D; van der Wildt, G J; Keemink, C J

    1989-03-01

    The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way.

  18. [THREE CASES OF DRUG-INDUCED PNEUMONIA CAUSED BY MESALAZINE].

    Science.gov (United States)

    Akiyama, Norimichi; Yokomura, Koshi; Nozue, Tsuyoshi; Abe, Takefumi; Matsui, Takashi; Suda, Takafumi

    2015-12-01

    We report three cases of drug-induced pneumonia caused by mesalazine. They were all diagnosed as ulcerative colitis and treated with mesalazine orally. Our three cases and literature review revealed that mesalazine-induced pneumonia resemble like eosinophilic pneumonia or organizing pneumonia and that have good prognosis with drug cessation or administration of corticosteroid. The patient of ulcerative colitis is increasing every year and it is anticipated that the patient with mesalazine-induced pneumonia may also increase. In the treatment of ulcerative colitis with mesalazine, we should pay attention with patient's cough or fever for early detection of drug-induced pneumonia.

  19. Visual contrast sensitivity in drug-induced Parkinsonism.

    Science.gov (United States)

    Bulens, C; Meerwaldt, J D; van der Wildt, G J; Keemink, C J

    1989-01-01

    The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way. PMID:2926418

  20. 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.

  1. 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...

  2. 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...

  3. 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.

  4. Imaging of Drug-induced Complications in the Gastrointestinal System.

    Science.gov (United States)

    McGettigan, Melissa J; Menias, Christine O; Gao, Zhenqiang J; Mellnick, Vincent M; Hara, Amy K

    2016-01-01

    Drug-induced injury commonly affects the gastrointestinal and hepatobiliary systems because of the mechanisms of absorption and metabolism. In pill esophagitis, injury is frequently related to direct contact with the esophageal mucosa, resulting in small superficial ulcers in the mid esophagus. Nonsteroidal anti-inflammatory drugs can lead to gastrointestinal tract ulcers and small bowel mucosal diaphragms (thin weblike strictures). Injury to the pancreatic and hepatobiliary systems can manifest as pancreatitis, acute or chronic hepatitis, cholestasis, or steatosis and steatohepatitis (which may progress to cirrhosis). Various drugs may also insult the hepatic vasculature, resulting in Budd-Chiari and sinusoidal obstructive syndromes. Focal lesions such as hepatic adenomas may develop after use of oral contraceptives or anabolic steroids. Ultrasonography, computed tomography, and magnetic resonance imaging can aid in diagnosis of drug-induced injuries and often are necessary to exclude other causes.

  5. Drug-induced liver injury: Is it somehow foreseeable?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino; Matteo Nicola Dario Di Minno; Domenico Capone

    2009-01-01

    The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes -450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

  6. 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.

  7. Sleep and sleepiness of fishermen on rotating schedules.

    Science.gov (United States)

    Gander, Philippa; van den Berg, Margo; Signal, Leigh

    2008-04-01

    Seafaring is a hazardous occupation with high death and injury rates, but the role of seafarer fatigue in these events is generally not well documented. The International Maritime Organization has identified seafarer fatigue as an important health and safety issue. Most research to date has focused on more regularly scheduled types of operations (e.g., merchant vessels, ferries), but there is relatively little information on commercial fishing, which often involves high day-to-day and seasonal variability in work patterns and workload. The present study was designed to monitor the sleep and sleepiness of commercial fishermen at home and during extended periods at sea during the peak of the hoki fishing season, with a view to developing better fatigue management strategies for this workforce. Sleep (wrist actigraphy and sleep diaries) and sleepiness (Karolinska Sleepiness Scale [KSS] before and after each sleep period) of 20 deckhands were monitored for 4-13 days at home and for 5-9 days at sea while working a nominal 12 h on/6 h off schedule. On the 12 h on/6 hoff schedule, there was still a clear preference for sleep at night. Comparing the last three days at home and the first three days at sea showed that fishermen were more likely to have split sleep at sea (Wilcoxon signed ranks p or= 7 on 24% of days at sea vs. 9% of days at home (Wilcoxon signed ranks p loss, and residual sleepiness after sleep, were much more common at sea than at home. The longer duration of trips during the peak of the fishing season increases the risk of performance impairment due to greater cumulative sleep loss than would be expected on typical three-day trips. Key fatigue management strategies in this environment include that fishermen report to work as well rested as possible. Once at sea, the day-to-day variability in activities due to uncontrollable factors, such as fishing success, repairing gear, and weather conditions, mean that contingency planning is required for managing

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

    Science.gov (United States)

    Cubeddu, Luigi X

    2016-01-01

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

  9. Interactions between antiparkinsonian drugs and ABCB1/P-glycoprotein at the blood-brain barrier in a rat brain endothelial cell model.

    Science.gov (United States)

    Vautier, Sarah; Milane, Aline; Fernandez, Christine; Buyse, Marion; Chacun, Helene; Farinotti, Robert

    2008-09-05

    Parkinson's disease is a neurodegenerative disorder that requires treatment by dopaminergic agonists, which may be responsible for central side effects. We hypothesized that the efflux transporter ABCB1/P-glycoprotein played a role in brain disposition of antiparkinsonian drugs and could control central toxicity. We aimed to evaluate antiparkinsonian drugs as ABCB1 substrates and/or inhibitors in rat brain endothelial cells GPNT, in order to predict potential clinical drug-drug interactions. Among the antiparkinsonian drugs tested, levodopa, bromocriptine, pergolide and pramipexole were ABCB1 substrates. However, only bromocriptine could inhibit ABCB1 functionality with an IC(50) of 6.71 microM on Rhodamine 123 uptake and an IC(50) of 1.71 microM on digoxine uptake. Thus, bromocriptine at 100 microM is responsible for an increase of levodopa intracellular transport of about 2.05-fold versus control. Therefore, we can conclude that bromocriptine is a potent drug for medicinal interactions in vitro. Hence, in patients with Parkinson's disease, these results may be considered to optimise treatments individually.

  10. 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.

  11. Daytime sleepiness and quality of life in peritoneal dialysis patients.

    Science.gov (United States)

    Bilgic, Ayse; Akman, Beril; Sezer, Siren; Arat, Zubeyde; Ozelsancak, Ruya; Ozdemir, Nurhan

    2011-12-01

    We aimed to compare automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) therapy with regard to patients' excessive daytime sleepiness (EDS) and quality of life (QOL). EDS was assessed with the Epworth Sleepiness Scale (ESS) and QOL with the Medical Outcomes Study 36-Item Short Form (SF-36) health survey. We included 59 patients (CAPD/APD, 30/29; male/female, 33/26; age, 45.3±15.8 years; dialysis duration, 42.0±33.6 months). The CAPD and APD groups were similar with respect to factors that affected sleep quality (age, sex, duration of PD), smoking, alcohol intake, socioeconomic status, body mass index, comorbid disease, and various laboratory parameters. Although one patient (3.3%) treated with CAPD and four patients (13.8%) treated with APD experienced EDS, there was no significant differences in ESS scores between the CAPD and APD patients. There was no difference in the SF-36 total and subscale scores when APD patients were compared with CAPD patients. The independent predictors of ESS were the serum albumin level (β= -2.04, P<0.01), total SF-36 score (β= 0.08, P=0.02), social functioning score (β= -2.47, P=0.01), and role-emotional subscale score (β= -1.12, P=0.05). The incidence of EDS was slightly higher in APD patients, but it did not negatively affect daily activities or QOL.

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

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    Angeliki Tsapanou

    2015-07-01

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

  13. Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

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    Carolina P. B. Gracitelli

    2016-01-01

    Full Text Available Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

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

    Science.gov (United States)

    Barajas, Frank P.

    2006-01-01

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

  15. The Role of Daytime Sleepiness in Psychosocial Outcomes after Treatment for Obstructive Sleep Apnea

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    Esther Yuet Ying Lau

    2013-01-01

    Full Text Available We investigated the role of daytime sleepiness and sleep quality in psychosocial outcomes of patients with obstructive sleep apnea (OSA treated with continuous positive airway pressure (CPAP. Thirty-seven individuals with moderate to severe OSA and compliant with CPAP treatment for at least 3 months were compared to 27 age- and education-matched healthy controls. The OSA group and the control group were studied with overnight polysomnography (PSG and compared on measures of daytime sleepiness (Epworth Sleepiness Scale, sleep quality (Pittsburg Sleep Quality Index, mood (Beck Depression Inventory, Profile of Mood States, and functional outcomes (Functional Outcomes of Sleep Questionnaire. After CPAP treatment, the OSA group improved on sleep quality and sleepiness. As a group, they did not differ from controls on sleep architecture after CPAP. The OSA group also showed significant improvements in functional outcomes and was comparable to controls on mood and functional outcomes. Persistent difficulties included lowered activity level and residual sleepiness in some individuals. Sleepiness was found to be a significant predictor of mood and affective states, while both sleepiness and sleep quality predicted functional outcomes. These results highlight the importance of assessment and intervention targeting psychosocial functioning and sleepiness in individuals with OSA after treatment.

  16. In silico modeling to predict drug-induced phospholipidosis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov; Sadrieh, Nakissa

    2013-06-01

    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.

  17. 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....

  18. Drug-induced fulminant hepatic failure in pregnancy.

    Science.gov (United States)

    Firoz, Tabassum; Webber, Douglas; Rowe, Hilary

    2015-12-01

    Liver disease in pregnancy can be classified as predating, co-incidental or unique to pregnancy. Medications are often overlooked as a significant cause of liver disease. We present the case of a 39-year-old patient who presented at 20 weeks with jaundice, elevated liver enzymes, and abnormal liver function progressing eventually to fulminant hepatic failure. The patient was on methyldopa and labetalol from 12 weeks' gestational age. Liver biopsy was consistent with drug-induced liver injury. Both methyldopa and labetalol have been associated with hepatotoxicity including liver failure. This case highlights the importance of including medications as a cause of liver failure in pregnant patients.

  19. 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.

  20. Diagnosis and classification of drug-induced autoimmunity (DIA).

    Science.gov (United States)

    Xiao, Xiao; Chang, Christopher

    2014-01-01

    Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.

  1. Drug-induced linear IgA bullous dermatosis.

    Science.gov (United States)

    Navi, Daniel; Michael, Daniel J; Fazel, Nasim

    2006-09-08

    A 73-year-old man was admitted to the University of California Davis Medical Center for treatment of a pleural effusion and congestive heart failure. His hospital course was complicated by asymptomatic sustained ventricular tachycardia requiring placement of an implantable cardiac defibrillator. The patient was treated with vancomycin and cefazolin during the procedure. After 3 days he developed tense vesicles over the dorsal aspect of the hands. Perilesional skin biopsy showed subepidermal cleavage with a neutrophilic infiltrate. Direct immunofluorescence revealed granular IgA and C3 deposition along the dermal epidermal junction. A diagnosis of drug-induced linear IgA bullous dermatosis secondary to vancomycin was established. Linear IgA bullous dermatosis is a rare autoimmune blistering disorder with clinical features that can overlap with bullous pemphigoid and dermatitis herpetiformis. Drug-induced linear IgA bullous dermatosis is a less common variant that is correspondingly less well characterized. Although a variety of medications have been implicated, vancomycin is the most common associated drug.

  2. The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth

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    Tamilselvan Subramani

    2013-01-01

    Full Text Available Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF, endothelin-1 (ET-1, angiotensin II (Ang II, connective tissue growth factor (CCN2/CTGF, insulin-like growth factor (IGF, and platelet-derived growth factor (PDGF appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth.

  3. 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.

  4. Occupational Injuries related to Sleepiness in Indian Traditional Industries

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    Ajeet Jaiswal

    2012-08-01

    Full Text Available A cross-sectional study was done to evaluate the rate of sleepiness and its relation to occupational injuries in Indian Traditional Industries. Data was collected using pretested and structured questionnaire about eight sleep habits, symptoms of depression, occupational injury due to fatigue, demographics, presence of diseases and lifestyle factors from 920 workers between the ages of 18-65 (mean 433.5 year in small scale industries. Occupational injury was assessed by asking subjects 'Have you ever been injured during your work, including minor scratches and cuts (Yes/ No? Both sleep and injury were assessed over the previous one year period. One-third of workers answered that they had experienced injury. Workers with sleep features of DIS, sleeping poorly at night, insufficient sleep, and insomnia had a significantly higher prevalence for injury after adjusting for multiple confounders. The findings suggest that poor nocturnal sleep habits are associated with self-reported occupational injury.

  5. Classification algorithms for predicting sleepiness and sleep apnea severity.

    Science.gov (United States)

    Eiseman, Nathaniel A; Westover, M Brandon; Mietus, Joseph E; Thomas, Robert J; Bianchi, Matt T

    2012-02-01

    Identifying predictors of subjective sleepiness and severity of sleep apnea are important yet challenging goals in sleep medicine. Classification algorithms may provide insights, especially when large data sets are available. We analyzed polysomnography and clinical features available from the Sleep Heart Health Study. The Epworth Sleepiness Scale and the apnea-hypopnea index were the targets of three classifiers: k-nearest neighbor, naive Bayes and support vector machine algorithms. Classification was based on up to 26 features including demographics, polysomnogram, and electrocardiogram (spectrogram). Naive Bayes was best for predicting abnormal Epworth class (0-10 versus 11-24), although prediction was weak: polysomnogram features had 16.7% sensitivity and 88.8% specificity; spectrogram features had 5.3% sensitivity and 96.5% specificity. The support vector machine performed similarly to naive Bayes for predicting sleep apnea class (0-5 versus >5): 59.0% sensitivity and 74.5% specificity using clinical features and 43.4% sensitivity and 83.5% specificity using spectrographic features compared with the naive Bayes classifier, which had 57.5% sensitivity and 73.7% specificity (clinical), and 39.0% sensitivity and 82.7% specificity (spectrogram). Mutual information analysis confirmed the minimal dependency of the Epworth score on any feature, while the apnea-hypopnea index showed modest dependency on body mass index, arousal index, oxygenation and spectrogram features. Apnea classification was modestly accurate, using either clinical or spectrogram features, and showed lower sensitivity and higher specificity than common sleep apnea screening tools. Thus, clinical prediction of sleep apnea may be feasible with easily obtained demographic and electrocardiographic analysis, but the utility of the Epworth is questioned by its minimal relation to clinical, electrocardiographic, or polysomnographic features.

  6. 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 (P<0.001). We identified that deprived nocturnal sleep, an irregular sleep-wake schedule and depression were the risk factors of EDS for both genders, 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).

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

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    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

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

    Science.gov (United States)

    Mansur, Antonio de Padua; Rocha, Marcos ABS; Leyton, Vilma; Takada, Julio Yashio; Avakian, Solange Desirée; Santos, Alexandre J; Novo, Gisele C; Nascimento, Arledson Lima; Muñoz, Daniel Romero; Rohlfs, Waldo J C

    2015-01-01

    Background 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. PMID:26761367

  9. Excessive sleepiness, sleep hygiene, and coping strategies among night bus drivers: A cross-sectional study

    Science.gov (United States)

    Krishnaswamy, Uma Maheswari; Chhabria, Mamta S.; Rao, Aditi

    2016-01-01

    Background: Sleep disruption and excessive sleepiness are the known consequences of shift work. The recent spate of night-time road and air accidents, with some being directly attributed to driver sleepiness prompted us to undertake this study. Aims: To screen for excessive sleepiness, coping practices, and post-shift sleep hygiene in night bus drivers. Settings and Design: This prospective study was carried out on night bus drivers of a public transport organization in Bengaluru, Karnataka, India. Materials and Methods: Bus drivers driving for ≥8 h at night were screened with the Epworth Sleepiness Scale (ESS) and a prevalidated shift work questionnaire. Statistical Analysis: Descriptive statistics were used to analyze the compiled data using Statistical Package for the Social Sciences (SPSS) version 20. Results: One hundred and eighty bus drivers aged 22–63 years were screened. Excessive Sleepiness: Although only 2 (1.1%) drivers scored above the cutoff on ESS, 10 (5.6%) and 103 (57.2%) drivers admitted to feeling sleepy during daytime and night driving respectively. None of the drivers admitted to causing accidents related to sleepiness. The coping strategies for nocturnal sleepiness included consuming coffee/tea (16.7%), chewing tobacco (12.8%), smoking (6.1%), and walking (3.9%). Post-Shift Sleep Practices: Post-shift sleep duration ranged between 1 h and 10 h. Twenty-six (14.4%) and 16 (8.9%) drivers had difficulty initiating and maintaining sleep, respectively, while 9 (5%) reported frequent awakening during daytime sleep. Conclusion and Implications: This study has demonstrated a high incidence of nocturnal sleepiness and daytime sleep disruption among night bus drivers, thus necessitating the need for education about shift work and alertness testing among shift workers in critical professions. PMID:28194081

  10. 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.

  11. Lupus in a patient with cystinosis: is it drug induced?

    Science.gov (United States)

    Eroglu, F K; Besbas, N; Ozaltin, F; Topaloglu, R; Ozen, S

    2015-11-01

    A 9-year-old girl with a diagnosis of cystinosis since 2 years of age, on cysteamine therapy, presented with complaints of serositis and arthritis, and laboratory tests revealed high antinuclear antibody titers with hypocomplementemia. Kidney biopsy was not consistent with lupus nephritis. With prednisolone treatment her complaints resolved and creatinine level decreased, but on follow-up, serological features of systemic lupus erythematosus (SLE) continued. Six years after cessation of prednisolone, lupus features were reactivated, with positive antihistone antibodies and ANCA. Coincidence of cystinosis and SLE is very rare, and to the best of our knowledge this is the fourth case reported in the literature. Physicians should be aware that cystinosis patients may have some autoimmune manifestations with features of true or drug-induced lupus. In the light of this case, pathophysiology and treatment are discussed.

  12. Possibly drug-induced palpable migratory arciform erythema*

    Science.gov (United States)

    Dantas, Fernando Luiz Teixeira; Valente, Neusa Yuriko Sakai; Veronez, Isis Suga; Kakizaki, Priscila; Leitão, Juliana Ribeiro; Fraga, Rafael Cavanellas

    2015-01-01

    Palpable migratory arciform erythema is an entity of unknown etiology, with few published cases in the literature. The clinical and histopathological features of this disease are difficult to be distinguished from those of Jessner’s lymphocytic infiltration of the skin, lupus erythematous tumidus and the deep erythema annulare centrifugum. We describe here the first two Brazilian cases of palpable migratory arciform erythema. The patients presented with infiltrated annular plaques and erythematous arcs without scales. These showed centrifugal growth before disappearing without scarring or residual lesions after a few days. They had a chronic course with repeated episodes for years. In addition, these cases provide evidence of a drug-induced etiology. PMID:26312680

  13. Role of dermatology in pharmacogenomics: drug-induced skin injury.

    Science.gov (United States)

    Borroni, Riccardo G

    2015-01-01

    Different individuals may respond diversely to the same drug, in terms of efficacy and toxicity. Adverse drug reactions cause about 6% of all hospital admissions and account for up to 9% of hospitalization costs. Drug-induced skin injury (DISI) is the most common presentation of adverse drug reactions, ranging from maculopapular eruptions to severe adverse cutaneous drug reactions (SCARs) with mortality of up to 40%. Specific genetic polymorphisms confer susceptibility to different types of DISI. Identifying patients genetically at risk for SCARs is one of the goals of pharmacogenomics. In this article, the aspects of clinical dermatology relevant to the pharmacogenetics of DISI are reviewed. Many SCARs are now preventable, with consequent reduction of morbidity, mortality and healthcare costs.

  14. Serious drug-induced liver disease secondary to ezetimibe

    Institute of Scientific and Technical Information of China (English)

    José Castellote; Javier Adza; Rosa Rota; Anna Girbau; Xavier Xiol

    2008-01-01

    Ezetimibe is the first member of a new family of lipidlowering drugs that inhibits uptake of dietary and biliary cholesterol. It was approved by the FDA in 2002for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years.Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce serious toxic hepatitis and prompt withdrawal is mandatory in case of a significant abnormality in liver testing after beginning or during treatment with ezetimibe.

  15. Pattern analysis of drug-induced skin diseases.

    Science.gov (United States)

    Justiniano, Hildamari; Berlingeri-Ramos, Alma C; Sánchez, Jorge L

    2008-08-01

    Drug eruptions are common adverse reactions to drug therapy and are a frequent reason for consultation in clinical practice. Even though any medication can potentially cause an adverse cutaneous reaction, some drugs are implicated more commonly than others. Histologically, drugs can elicit a variety of inflammatory disease patterns in the skin and panniculus, no pattern being specific for a particular drug. The most common pattern elicited by systemically administered medications is the perivascular pattern. Psoriasiform or granulomatous patterns are rarely caused by medications. The usual histologic patterns of drug eruptions are discussed in this review using the basic patterns of inflammatory diseases. Clinicopathologic correlation is established for relevant patterns. However, the changes of drug-induced skin disease must be made considering clinical presentation, histopathological analysis, and course of the disease.

  16. Genetic association studies in drug-induced liver injury.

    Science.gov (United States)

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  17. Driver Sleepiness and Risk of Car Crashes in Shenyang, a Chinese Northeastern City: Population-based Case-control Study

    Institute of Scientific and Technical Information of China (English)

    GAI-FEN LIU; SONG HAN; DUO-HONG LIANG; FENG-ZHI WANG; XIN-ZHU SHI; JIAN YU; ZHENG-LAI WU

    2003-01-01

    To estimate the association of driver sleepiness with the risk of car crashes.Methods A population-based case-control study was conducted in Shenyang, a northeastern city in China, between November 2001 and July 2002. The case group comprised 406 car drivers involved in crashes, and 438 car drivers recruited at randomly selected sites, and on the day of week, and the time of day when they were driving on highways in the study region during the study period were used as control groups. Face-to-face interviews with drivers were conducted according to a well-structured questionnaire covering the circumstances of their current trip and their background information.Stanford sleepiness scale and Epworth sleepiness scale were used to quantify acute sleepiness and chronic sleepiness respectively. Results There was a strong association between chronic sleepiness and the risk of car crash. Significantly increased risk of crash was associated with drivers who identified themselves as sleepy (Epworth sleepiness score ≥ 10 vs <10; adjusted odds ratio 2.07, 95%confidence interval 1.30 to 3.29), but no increased risk was associated with measures of acute sleepiness. Conclusions Chronic sleepiness in car drivers significantly increases the risk of car crash. Reductions in road traffic injuries may be achieved if fewer people drive when they are sleepy.

  18. PTTG1 attenuates drug-induced cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yunguang Tong

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

  19. Ocular anatomy and retinal photoreceptors in a skink, the sleepy lizard (Tiliqua rugosa).

    Science.gov (United States)

    New, Shaun T D; Hemmi, Jan M; Kerr, Gregory D; Bull, C Michael

    2012-10-01

    The Australian sleepy lizard (Tiliqua rugosa) is a large day-active skink which occupies stable overlapping home ranges and maintains long-term monogamous relationships. Its behavioral ecology has been extensively studied, making the sleepy lizard an ideal model for investigation of the lizard visual system and its specializations, for which relatively little is known. We examine the morphology, density, and distribution of retinal photoreceptors and describe the anatomy of the sleepy lizard eye. The sleepy lizard retina is composed solely of photoreceptors containing oil droplets, a characteristic of cones. Two groups could be distinguished; single cones and double cones, consistent with morphological descriptions of photoreceptors in other diurnal lizards. Although all photoreceptors were cone-like in morphology, a subset of photoreceptors displayed immunoreactivity to rhodopsin-the visual pigment of rods. This finding suggests that while the morphological properties of rod photoreceptors have been lost, photopigment protein composition has been conserved during evolutionary history.

  20. Excessive Daytime Sleepiness and Epilepsy: A Systematic Review

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    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.

  1. Excessive daytime sleepiness and epilepsy: a systematic review.

    Science.gov (United States)

    Giorelli, Andre S; Passos, Pâmela; Carnaval, Thiago; Gomes, Marleide da Mota

    2013-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  3. In vitro validation of drug-induced phospholipidosis.

    Science.gov (United States)

    Park, Sora; Choi, You-Jin; Lee, Byung-Hoon

    2012-01-01

    Intracellular accumulation of phospholipids with lamellar bodies is a hallmark of drug-induced phospholipidosis (PLD) which is caused by impaired phospholipid metabolism of the lysosome. Although it remains uncertain whether PLD is associated with the adverse effects, sponsors generally terminate the development of a candidate drug when PLD is observed in an organ. For drugs that are used without serious adverse events, there should be labels indicating that the drug can induce PLD. We conducted LipidTox and NBD-PE assays for detecting PLD to compare and validate the methods. In the case of contrary results in both assays, electron microscopy was performed to confirm the data. We selected 12 chemicals and divided them into 4 categories: P+S+, PLD and steatosis positive; P+/S-, PLD positive and steatosis negative; P-S+, PLD negative and steatosis positive; P-/S-, PLD and steatosis negative. In general, results showed very good agreement with the known information with some minor discrepancies. LipidTox assay is proven to be a very sensitive method. Considering the contrary results of acetaminophen and menadione in LipidTox and the NBD-PE assay, the combination of two methods using different phospholipids is advantageous to reduce false positives. The finding that acetaminophen was positive in LipidTos assay and increased the frequency of lamellar body implies that acetaminophen is a weak inducer of PLD.

  4. Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.

    Science.gov (United States)

    Frommeyer, Gerrit; Eckardt, Lars

    2016-01-01

    Drug-induced ventricular tachyarrhythmias can be caused by cardiovascular drugs, noncardiovascular drugs, and even nonprescription agents. They can result in arrhythmic emergencies and sudden cardiac death. If a new arrhythmia or aggravation of an existing arrhythmia develops during therapy with a drug at a concentration usually considered not to be toxic, the situation can be defined as proarrhythmia. Various cardiovascular and noncardiovascular drugs can increase the occurrence of polymorphic ventricular tachycardia of the 'torsade de pointes' type. Antiarrhythmic drugs, antimicrobial agents, and antipsychotic and antidepressant drugs are the most important groups. Age, female sex, and structural heart disease are important risk factors for the occurrence of torsade de pointes. Genetic predisposition and individual pharmacodynamic and pharmacokinetic sensitivity also have important roles in the generation of arrhythmias. An increase in spatial or temporal dispersion of repolarization and a triangular action-potential configuration have been identified as crucial predictors of proarrhythmia in experimental models. These studies emphasized that sole consideration of the QT interval is not sufficient to assess the proarrhythmic risk. In this Review, we focus on important triggers of proarrhythmia and the underlying electrophysiological mechanisms that can enhance or prevent the development of torsade de pointes.

  5. 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.

  6. 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.

  7. Drug-induced secretory diarrhea: A role for CFTR.

    Science.gov (United States)

    Moon, Changsuk; Zhang, Weiqiang; Sundaram, Nambirajan; Yarlagadda, Sunitha; Reddy, Vadde Sudhakar; Arora, Kavisha; Helmrath, Michael A; Naren, Anjaparavanda P

    2015-12-01

    Many medications induce diarrhea as a side effect, which can be a major obstacle to therapeutic efficacy and also a life-threatening condition. Secretory diarrhea can be caused by excessive fluid secretion in the intestine under pathological conditions. The cAMP/cGMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) is the primary chloride channel at the apical membrane of intestinal epithelial cells and plays a major role in intestinal fluid secretion and homeostasis. CFTR forms macromolecular complexes at discreet microdomains at the plasma membrane, and its chloride channel function is regulated spatiotemporally through protein-protein interactions and cAMP/cGMP-mediated signaling. Drugs that perturb CFTR-containing macromolecular complexes in the intestinal epithelium and upregulate intracellular cAMP and/or cGMP levels can hyperactivate the CFTR channel, causing excessive fluid secretion and secretory diarrhea. Inhibition of CFTR chloride-channel activity may represent a novel approach to the management of drug-induced secretory diarrhea.

  8. "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

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

    OpenAIRE

    Ramesh Vijay; Nair Deepti; Zhang Shelley X L; Hakim Fahed; Kaushal Navita; Kayali Foaz; Wang Yang; Li Richard C; Carreras Alba; Gozal David

    2012-01-01

    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...

  10. Drug-Induced Gingival Overgrowth: The Genetic Dimension

    Science.gov (United States)

    Charles, Noronha Shyam Curtis; Chavan, Rahul; Moon, Ninad Joshirao; Nalla, Srinivas; Mali, Jaydeepchandra; Prajapati, Anchal

    2014-01-01

    Background: Currently, the etiology of drug-induced gingival overgrowth is not entirely understood but is clearly multifactorial. Phenytoin, one of the common drugs implicated in gingival enlargement, is metabolized mainly by cytochrome P450 (CYP)2C9 and partly by CYP2C19. The CYP2C9 and CYP2C19 genes are polymorphically expressed and most of the variants result in decreased metabolism of the respective substrates. Aims: The present study was undertaken to investigate the influence of the CYP2C9*2 and *3 variant genotypes on phenytoin hydroxylation in subjects diagnosed with epilepsy from South India, thus establishing the genetic polymorphisms leading to its defective hydroxylation process. Materials and Methods: Fifteen epileptic subjects, age 9 to 60 years were included in the study. Among the study subjects, 8 were males and 7 were females. Genomic DNA was extracted from patients’ blood using Phenol-chloroform method and genotyping was done for CYP2C9 using customized TaqMan genotyping assays on a real time thermocycler, by allelic discrimination method. The genetic polymorphisms *1, *2 and *3 on CYP2C9 were selected based on their function and respective allele frequencies in Asian subcontinent among the Asian populations. Results: CYP2C9*1*2 and CYP2C9*3/*3 were identified with equal frequency in the study population. There were seven subjects with CYP2C9*1/*2 genotype (heterozygous mutant), one subject with CYP2C9*1/*1 (wild type) and seven study subjects with CYP2C9*3/*3 (homozygous mutant). Conclusion: The results obtained in the present study will be helpful in the medical prescription purposes of phenytoin, and a more personalized patient approach with its administration can be advocated. PMID:25317394

  11. Drug-induced liver injury and drug development: industry perspective.

    Science.gov (United States)

    Regev, Arie

    2014-05-01

    Despite intensive ongoing research, drug-induced live injury (DILI) remains a serious issue for care providers and patients, and has been a major cause of drug withdrawal and non-approval by regulatory authorities in the past 50 years. Consequently, DILI remains a major concern for the pharmaceutical industry and a leading cause for attrition during drug development. In most instances, severe DILI is an uncommon idiosyncratic reaction, which typically does not present during preclinical phases or early clinical phases of drug development. In the majority of cases, drugs that caused severe DILI in humans have not shown clear and consistent hepatotoxic signals in preclinical assessment including animal studies, cell cultures, or other methods. Despite intensive efforts to develop better biomarkers that would help in predicting DILI risk in earlier phases of drug development, such biomarkers are currently not supported by sufficient evidence and are not yet available for routine use by drug makers. Due to the lack of effective and accurate methods for prediction of idiosyncratic DILI during preclinical phases of drug development, different drug makers have adopted different approaches, which are often not supported by strong systematic evidence. Based on growing experience, it is becoming increasingly evident that milder forms of liver injury occurring during clinical development, when assessed correctly, may significantly enhance our ability to predict the drug's potential to cause more severe liver injury postmarketing. Strategies based on this concept have been adopted by many drug makers, and are being increasingly implemented during drug development. Meticulous causality assessment of individual hepatic cases and adherence to strict hepatic discontinuation rules are critical components of this approach and have to rely on thorough clinical evaluation and occasionally on assessment by liver experts experienced with DILI and drug development.

  12. 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.

  13. Effects of Shift Work on Cognitive Performance, Sleep Quality, and Sleepiness among Petrochemical Control Room Operators.

    Science.gov (United States)

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

    2016-02-03

    Shift work is associated with both sleepiness and reduced performance. The aim of this study was to examine cognitive performance, sleepiness, and sleep quality among petrochemical control room shift workers. Sixty shift workers participated in this study. Cognitive performance was evaluated using a number of objective tests, including continuous performance test, n-back test, and simple reaction time test; sleepiness was measured using the subjective Karolinska Sleepiness Scale (KSS); and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. ANCOVA, t-test, and repeated-measures ANOVA were applied for statistical analyses, and the significance level was set at p sleep quality on both day and night shifts, and there were significant differences between the day and night shifts in terms of subjective sleep quality and quantity (p sleep, induced cognitive performance decline at the end of both day and night shifts, and increased sleepiness in night shift. It, thus, seems necessary to take ergonomic measures such as planning for more appropriate shift work and reducing working hours.

  14. Conjoint influence of mind-wandering and sleepiness on task performance.

    Science.gov (United States)

    Stawarczyk, David; D'Argembeau, Arnaud

    2016-10-01

    Recent research suggests that sleepiness and mind-wandering-the experience of thoughts that are both stimulus-independent and task-unrelated-frequently co-occur and are both associated with poorer cognitive functioning. Whether these two phenomena have distinguishable effects on task performance remains unknown, however. To investigate this question, we used the online experience sampling of mind-wandering episodes and subjective sleepiness during a laboratory task (the Sustained Attention to Response Task; SART), and also assessed mind-wandering frequency and sleep-related disturbances in daily life using self-report questionnaires. The results revealed that the tendency to experience mind-wandering episodes during the SART and daily life was associated with higher levels of daytime sleepiness and sleep-related disturbances. More important, however, mind-wandering and sleepiness were independent predictors of SART performance at both the within- and between-individuals levels. These findings demonstrate that, although mind-wandering and sleepiness frequently co-occur, these two phenomena have distinguishable and additive effects on task performance. (PsycINFO Database Record

  15. Unusual case of drug-induced cholestasis due to glucosamine and chondroitin sulfate

    Institute of Scientific and Technical Information of China (English)

    Stephen; Ip; Rachel; Jeong; David; F; Schaeffer; Eric; M; Yoshida

    2015-01-01

    Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.

  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. [Analysis of risk factors of drug-induced lung injury in patients receiving gemcitabine treatment].

    Science.gov (United States)

    Nakamichi, Hidenori; Fujita, Tetsuo; Tsuji, Daiki; Atsumi, Ichiko; Totsuka, Kasumi; Suzuki, Rina; Miki, Yoshihiro; Tomita, Kazuhiro; Nakamura, Hidenori; Shiokawa, Mitsuru

    2012-05-01

    Gemcitabine hydrochloride is a very safe medicine that even outpatients can be administered, and the bone marrow depression that is the dose limiting factor remains moderate and does not need special treatment, although it is confirmed in most cases. Meanwhile, caution is required because there is a possibility of drug-induced lung injury and death due to high frequency, compared with the appearance rate described in the packaging insertion. We investigated the clinical background of a patient in whom drug-induced lung injury appeared, and clarified the risk factor by administering gemcitabine hydrochloride. Males, people aged 65 or over, those with a smoking history and those undergoing first-line chemotherapy treatment are at risk of drug-induced lung injury. Attention must be paid to the occurrence of drug-induced lung injury, to examining the clinical course, the chest image, and the blood test, and to do earlier detection, the offending medicine discontinuance, and beginning of the treatment.

  19. Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria

    OpenAIRE

    Criado, Paulo Ricardo; CRIADO, Roberta Fachini Jardim; TAKAKURA, CLEUSA F.H.; Pagliari, Carla; SOTTO, Mirian Nacagami; Cidia VASCONCELLOS

    2012-01-01

    BACKGROUND: Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. OBJECTIVE: The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using ...

  20. Chronic headaches and sleepiness caused by facial soap (containing hydrolyzed wheat proteins)-induced wheat allergy.

    Science.gov (United States)

    Iseki, Chifumi; Kawanami, Toru; Tsunoda, Takahiko; Chinuki, Yuko; Kato, Takeo

    2014-01-01

    A 38-year-old woman was suffering from irregular headaches and sleepiness. She had used soap containing Glupearl 19S (hydrolyzed wheat proteins) every day for approximately one year and had experienced an episode of rash eruption on her face seven months ago. Wheat-specific IgE antibodies were detected in her serum. A Western blot analysis revealed a high titer of IgE antibodies against Glupearl 19S and wheat proteins. The patient was sensitive to these compounds in a skin prick test. After avoiding eating wheat, her headaches and sleepiness disappeared. A hidden food allergy is a possible cause of these symptoms.

  1. 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.

  2. 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)…

  3. Sleep and sleepiness among first-time postpartum parents: a field- and laboratory-based multimethod assessment.

    Science.gov (United States)

    Insana, Salvatore P; Montgomery-Downs, Hawley E

    2013-05-01

    The study aim was to compare sleep, sleepiness, fatigue, and neurobehavioral performance among first-time mothers and fathers during their early postpartum period. Participants were 21 first-time postpartum mother-father dyads (N = 42) and seven childless control dyads (N = 14). Within their natural environment, participants completed 1 week of wrist actigraphy monitoring, along with multi-day self-administered sleepiness, fatigue, and neurobehavioral performance measures. The assessment week was followed by an objective laboratory-based test of sleepiness. Mothers obtained more sleep compared to fathers, but mothers' sleep was more disturbed by awakenings. Fathers had greater objectively measured sleepiness than mothers. Mothers and fathers did not differ on subjectively measured sleep quality, sleepiness, or fatigue; however, mothers had worse neurobehavioral performance than fathers. Compared to control dyads, postpartum parents experienced greater sleep disturbance, sleepiness, and sleepiness-associated impairments. Study results can inform social policy, postpartum sleep intervention development, and research on postpartum family systems and mechanisms that propagate sleepiness.

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

    Science.gov (United States)

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

    2016-01-01

    Objective To investigate the evolution over 15 years of sleep schedules, sleepiness at the wheel and driving risk among highway drivers. Methods Comparative survey including questions on usual sleep schedules and before the trip, sleepiness at the wheel, the Epworth sleepiness scale, Basic Nordic Sleep Questionnaire (BNSQ) and a travel questionnaire. Results 80% of drivers stopped by the highway patrol agreed to participate in both studies with a total of 3545 drivers in 2011 and 2196 drivers in 1996 interviewed. After standardisation based on sex, age and mean annual driving distance, drivers in 2011 reported shorter sleep time on week days (p15 indicating severe sleepiness. Conclusions Even if drivers in 2011 reported good sleep hygiene prior to a highway journey, drivers have reduced their mean weekly sleep duration over 15 years and have a higher risk of sleepiness at the wheel. Sleep hygiene for automobile drivers remains an important concept to address. PMID:28003284

  5. 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

    2016-04-26

    This study examined the association of subjective nighttime sleep quality and daytime sleepiness with cognitive impairment in 105 adults (old) and 167 elders (≥ 60 years old) with heart failure. Nighttime 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.

  6. 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,…

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

    OpenAIRE

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

    2009-01-01

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

  8. The Psychosocial Problems of Children with Narcolepsy and Those with Excessive Daytime Sleepiness of Uncertain Origin

    Science.gov (United States)

    Stores, Gregory; Montgomery, Paul; Wiggs, Luci

    2007-01-01

    Background: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong…

  9. 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…

  10. 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

  11. 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

    Background 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. Methods and Findings 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. Conclusion 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

  12. 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.

  13. Daytime sleepiness and sleep habits as risk factors of traffic accidents in a group of Turkish public transport drivers

    Science.gov (United States)

    Özer, Cahit; Etcibaşı, Şeref; Öztürk, Levent

    2014-01-01

    Aim: To explore the association of daytime sleepiness, sleep complaints and sleep habits with self-reported car crashes among public transport drivers. Methods: A cross-sectional descriptive study was carried out on male professional public drivers in two different cities using a validated, self-administered sleep questionnaire which comprised of symptoms suggesting sleep disorders, a subjective report of daytime sleepiness and driving characteristics. The subjects (mean age±SD, 40±11 years) were divided into two groups: (1) accident group and (2) no accident group. Results: Forty nine (15.3%) of the 320 public drivers reported that they had at least one sleepiness related motor vehicle accident and/or near-missed accident (Group 1). The mean age, body mass index and annual distance driven were similar in both groups. Although Group 1 reported less sleep time per night, more witnessed apneas, abnormal sleep, alcohol use and had higher mean Epworth Sleepiness Scale scores than Group 2, multivariate analysis of risk factors revealed that only daytime sleepiness increase the risk of traffic accidents [OR: 1.32 (1.19-1.47)]. Conclusion: These results suggest that self-reported sleepiness is a predictive sign of traffic accidents due to driver sleepiness. PMID:24482715

  14. Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator

    Science.gov (United States)

    Okada, Jun-ichi; Yoshinaga, Takashi; Kurokawa, Junko; Washio, Takumi; Furukawa, Tetsushi; Sawada, Kohei; Sugiura, Seiryo; Hisada, Toshiaki

    2015-01-01

    To save time and cost for drug discovery, a paradigm shift in cardiotoxicity testing is required. We introduce a novel screening system for drug-induced arrhythmogenic risk that combines in vitro pharmacological assays and a multiscale heart simulator. For 12 drugs reported to have varying cardiotoxicity risks, dose-inhibition curves were determined for six ion channels using automated patch clamp systems. By manipulating the channel models implemented in a heart simulator consisting of more than 20 million myocyte models, we simulated a standard electrocardiogram (ECG) under various doses of drugs. When the drug concentrations were increased from therapeutic levels, each drug induced a concentration-dependent characteristic type of ventricular arrhythmia, whereas no arrhythmias were observed at any dose with drugs known to be safe. We have shown that our system combining in vitro and in silico technologies can predict drug-induced arrhythmogenic risk reliably and efficiently. PMID:26601174

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

  16. Subjective sleepiness in heart failure patients with sleep-related breathing disorder

    Institute of Scientific and Technical Information of China (English)

    WANG Han-qiao; CHEN Gang; LI Jing; HAO Shu-min; GU Xin-shun; PANG Jiang-na; FU Xiang-hua

    2009-01-01

    Background Previous studies show that sleep-related breathing disorder (SRBD) is common in patients with heart failure (HF) and is associated with increased mortality. This study aimed to determine whether there was significant difference of subjective daytime sleepiness between HF patients with and without SRBD.Methods We enrolled, prospectively, 195 consecutive HF patients with left ventricular ejection fractions (LVEF)≮45%and all subjects underwent polysomnography to measure the sleep structure between 2005 and 2008. Patients were then assigned to those with SRBD including obstructive and central sleep apnea (apnea-hypopnea index (AHI)≯5/hour of sleep) and those without SRBD (AHI<5/hour) according to the sleep study. The subjective sleepiness was assessed withEpworth sleepiness scale (ESS).Results Among 195 HF patients, the prevalence of obstructive sleep apnea (OSA) was 53% and of central sleep apnea (CSA) was 27%. There was no significant difference of ESS scores between patients without SRBD (NSA) and with SRBD (NSA vs OSA: 6.7±0.6 VS 7.6±0.4, P=0.105 and NSA vs CSA: 6.7±0.6 vs 7.4±0.5, ,P=0.235, respectively),indicating that SRBD patients had no more subjective daytime sleepiness. Compared with NSA, patients with SRBD had increased arousal index (Arl) (NSA vs OSA: 14.1±1.4 vs 26.3±1.5, P <0.001 and NSA vs CSA: 14.1±1.4 vs 31.3±3.5, P <0.001, respectively), more awake number after sleep onset (NSA vs OSA: 19.2±1.5 vs 26.2±1.4, P=0.01 and NSA vs CSA: 19.2±1.5 vs 36.9±4.4, P <0.001, respectively), and reduced proportion of slow-wave sleep (SWS) (NSA vs OSA: 13.8±1.7 vs 9.3±0.7, ,P=0.024 and NSA vs CSA: 13.8±1.7 vs 8.9±0.9, P=0.024, respectively). Conclusions OSA and CSA remain common in patients with HF on optimal contemporary therapy. Patients with both HF and SRBD have no significant subjective daytime sleepiness compared with patients without SRBD, despite of significantly increased awake number, arousal and decreased proportion of deep

  17. Correlation of Epworth Sleepiness Scale with multiple sleep latency test and its diagnostic accuracy in assessing excessive daytime sleepiness in patients with obstructive sleep apnea hypopnea syndrome

    Institute of Scientific and Technical Information of China (English)

    CAI Si-jie; CHEN Rui; ZHANG Yan-lin; XIONG Kang-ping; LIAN Yi-xin; LI Jie; SHEN Jiu-cheng

    2013-01-01

    Background Excessive daytime sleepiness (EDS) is often associated with obstructive sleep apnea hypopnea syndrome (OSAHS) and contributes to a number of comorbidities in these patients.Therefore,eady detection of EDS is critical in disease management.We examined the association between Epworth Sleepiness Scale (ESS) and multiple sleep latency test (MSLT) and diagnostic accuracy of ESS in assessing EDS in OSAHS patients.Methods The ESS,MSLT and overnight polysomnography were administered to 107 Chinese patients to assess EDS and its correlations with polysomnographic parameters.The diagnostic accuracy of ESS in classifying EDS (mean sleep latency (MSL) <10 minutes) was evaluated by calculating the area under ROC curve.Results As the severity of OSAHS increased,MSL decreased with increase in ESS score.Conversely,patients with worsening EDS (shorter MSL) were characterized by advanced nocturnal hypoxaemia and sleep disruption compared to those with normal MSL,suggesting EDS is associated with more severe OSAHS.There was a negative correlation between ESS score and MSL and both moderately correlated with some polysomnographic nocturnal hypoxaemic parameters.The area under ROC curve of ESS for identifying EDS was 0.80 (95% C/:0.71 to 0.88) and ESS score >12provided the best predictive value with a sensitivity of 80% and specificity of 69%.Conclusion The ESS score moderately correlates with MSL and our ROC study supports ESS as a screening strategy for assessing EDS in OSAHS.

  18. Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness

    DEFF Research Database (Denmark)

    Penner, Iris-Katharina; Sivertsdotter, Eva Catharina; Celius, Elisabeth G

    2015-01-01

    BACKGROUND: Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful...... of the two latter symptoms and changes in fatigue was analyzed. RESULTS: After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed...... patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness...

  19. Fatigue and daytime sleepiness in patients with myotonic dystrophy type 1: to lump or split?

    Science.gov (United States)

    Laberge, Luc; Dauvilliers, Yves; Bégin, Paul; Richer, Louis; Jean, Stéphane; Mathieu, Jean

    2009-06-01

    We assessed the relationship and clinical correlates of fatigue and Excessive Daytime Sleepiness (EDS) in 200 myotonic dystrophy type 1 (DM1) patients by means of questionnaire and neuropsychological evaluation. Fatigue levels were higher in patients with EDS and daytime sleepiness levels higher in patients with excessive fatigue. However, EDS without fatigue was rarely observed. Also, DM1 patients with fatigue (with or without EDS) showed greater muscular impairment, CTG repeats, abnormalities regarding personality, depressive symptoms and lower health-related quality of life (HRQoL) than patients without these symptoms. These findings do not readily support the contention that fatigue and EDS constitute distinct clinical manifestations in DM1. Clinicians should systematically evaluate both symptoms since fatigue and EDS have a greater impact on HRQoL than fatigue alone. However, specific rating scales for fatigue in DM1 have yet to be devised.

  20. Correlates of excessive daytime sleepiness in community-dwelling older adults: an exploratory study.

    Science.gov (United States)

    Lima, Camila Astolphi; Soares, Wuber Jefferson de Souza; Bilton, Tereza Loffredo; Dias, Rosângela Corrêa; Ferrioll, Eduardo; Perracini, Monica Rodrigues

    2015-01-01

    Excessive daytime sleepiness (EDS) imposes a wide range of adverse health-related outcomes in older people, such as disability, which impair everyday activities and may increase the risk of fall. Few studies have explored EDS in Brazilian older people living in the community who are typically cared in primary health services. This study aims to investigate the prevalence of EDS and its sociodemographic, physical and mental health correlates among community-dwelling older adults. This is an exploratory, population-based study derived from Frailty in Brazilian Older Adults (FIBRA) study including adults aged 65 years and older. Participants with a score ≥ 11 points on the Epworth Sleepiness Scale were considered as having excessive daytime sleepiness. A structured, multidimensional questionnaire was used to investigate sociodemographic, physical and mental health, and self-rated health variables. The sample was composed of 776 older adults, of whom 21% (n = 162) presented excessive daytime sleepiness. Multivariate regression analysis revealed that EDS is associated with obesity (OR = 1.50; 95%CI 1.02 - 2.20), urinary incontinence (OR = 1.53; 95%CI 1.01 - 2.31), poor self-rated health (OR = 1.54; 95%CI 1.06 - 2.24), and depression symptoms (OR = 1.49; 95%CI 1.00 - 2.20). Our results suggest that healthcare professionals should identify older adults with EDS and implement intervention strategies to minimize the negative impact of the co-occurrence of this condition with obesity, depression and urinary incontinence over health and quality of life.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Samuel J Bolitho

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

  3. 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...

  4. Subjective sleep quality and daytime sleepiness in late midlife and their association with age-related changes in cognition

    DEFF Research Database (Denmark)

    Waller, Katja Linda; Mortensen, Erik Lykke; Avlund, Kirsten

    2016-01-01

    UNLABELLED: In an increasingly aged population, sleep disturbances and neurodegenerative disorders have become a major public health concern. Poor sleep quality and cognitive changes are complex health problems in aging populations that are likely to be associated with increased frailty, morbidity......) or cognitively impaired (N = 92). METHODS: The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale measured subjective sleep quality and daytime sleepiness, respectively. Depressive symptoms were determined using Beck's Depression Inventory (BDI-II). A neuropsychological battery was administered...

  5. 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 socio-demographic characteristics, sleep quality characteristics, CMDs, and other lifestyle behaviors. Results The prevalence of CMDs was 24.3% (95% 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=0.034). Excessive daytime sleepiness (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. Conclusion Given the adverse health consequences associated with both sleep disorders and CMDs, improving sleep hygiene among college students is imperative to public health. PMID:24810953

  6. 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.

  7. Daytime Sleepiness and Parkinson’s Disease: The Contribution of the Multiple Sleep Latency Test

    Directory of Open Access Journals (Sweden)

    Marcelo Ataide

    2014-01-01

    Full Text Available Background. Sleep disorders are major nonmotor manifestations of patients with Parkinson’s disease (PD, and excessive daytime sleepiness (EDS is one of the most common symptoms. Objective. We reviewed a current literature concerning major factors that influence EDS in PD patients, using Multiple Sleep Latency Test (MSLT. Methods. A Medline search found 23 studies. Results. The presence of EDS was observed in 12.7% to 47% in patients without complaints of daytime sleepiness and 47% to 66.7% with complaints of daytime sleepiness. Despite being recognized by several authors, major factors that influence EDS, such as severity of motor symptoms, use of dopaminergic medications, and associated sleep disturbances, presented contradictory data. Conclusions. Available data suggest that the variability of the results may be related to the fact that it was conducted with a small sample size, not counting the neuropathological heterogeneity of the disease. Thus, before carrying out longitudinal studies with significant samples, careful analysis should be done by assigning a specific agent on the responsibility of EDS in PD patients.

  8. Examination of daytime sleepiness and cognitive performance testing in patients with primary insomnia.

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    Hong Liu

    Full Text Available While individuals with insomnia consistently complain of cognitive impairment, previous studies on the effect of insomnia on objective measures of cognitive function have obtained ambiguous results. The relationship between daytime sleepiness and cognitive manifestations in insomnia patients is not clear.Thirty-six primary insomnia patients (PIPs and 26 good sleep controls (GSCs with age and gender matched manner were included in the study. Participants underwent an overnight polysomnography followed by a multiple sleep latency test (MSLT and an examination of the attention network test (ANT. ANT reflected three attentional networks including alerting, orienting and executive control. According to whether accompanied with excessive daytime sleepiness (EDS, the insomnia group were subdivided into PIPs with EDS (n = 12, score on MSLT<10 min and PIPs without EDS (n = 24, score on MSLT≥10 min.PIPs only performed worse on executive control function than GSCs in ANT. PIPs with EDS had longer overall reaction time (RT related to PIPs without EDS. Further analyses with Pearson correlation analysis showed a significant negative correlation between the overall RT and MSLT latency in insomniacs (r = -0.444, p<0.01, whereas no such correlation was found in controls.Results suggest that PIPs do show executive control function deficits compared with GSCs. Daytime sleepiness in terms of MSLT latency was associated with poor cognitive manifestations in patients with insomnia.

  9. Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: A case series

    NARCIS (Netherlands)

    D.M.W. Balak (Deepak); J.N.B. Bavinck (Jan Nico Bouwes); De Vries, A.P.J. (Aiko P. J.); Hartman, J. (Jenny); Martino Neumann, H.A. (Hendrik A.); R. Zietse (Bob); H.B. Thio (Bing)

    2016-01-01

    textabstractBackground: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fan

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

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    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.

  11. Topical drug-induced subacute cutaneous lupus erythematosus isolated to the hands

    Science.gov (United States)

    Ramachandran, Sarika M; Leventhal, Jonathan S; Franco, Loren G; Mir, Adnan; Walters, Ruth F; Franks, Andrew G

    2017-01-01

    Subacute cutaneous lupus erythematosus (SCLE) is a well-defined subtype of lupus erythematosus, characterised by photosensitivity, annular and/or psoriasiform lesions, variable systemic involvement and presence of circulating SSA/anti-Ro antibodies. SCLE may be idiopathic or drug-induced. Both the idiopathic and drug-induced forms of SCLE are analogous in their clinical, serological and histological features. Drug-induced SCLE has been reported with various oral agents, but to our knowledge this is the first reported case due to a topical medication. A 34-year-old female foot masseuse presented with a 2-month history of scaly, erythematous lesions isolated to the dorsal hands and interdigital spaces. She had used topical terbinafine, a topical antifungal cream, to her clients’ feet for a number of years. ANA and anti-SSA/Ro antibodies were positive. Physical examination, serology and histopathology were consistent with SCLE. We propose that our patient's unique presentation of SCLE may be explained by a prolonged occupational exposure to topical terbinafine as a foot masseuse. While oral terbinafine is a drug known to cause drug-induced SCLE, to our knowledge, this is the first topically induced form of the disease. PMID:28331627

  12. Sonolência e acidentes automobilísticos Sleepiness and motor vehicle accidents

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    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

  13. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

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    Yuko Ono

    2016-01-01

    Full Text Available An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST for carbamazepine, human herpes virus-6 (HHV-6 IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times. Following treatment, liver and renal function improved and the erythema disappeared.

  14. Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine.

    Science.gov (United States)

    Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis

    2017-02-01

    Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

  15. Drug-induced subacute cutaneous lupus erythematosus associated with nab-paclitaxel therapy.

    Science.gov (United States)

    Lamond, N W D; Younis, T; Purdy, K; Dorreen, M S

    2013-10-01

    Drug-induced lupus erythematosus (dile) syndromes are documented complications of chemotherapeutic agents, including paclitaxel. Subacute cutaneous lupus erythematosus (scle) is a distinct dile syndrome presenting with characteristic annular or papulosquamous skin lesions in a photosensitive distribution with associated high anti-ssa titres. Previously, dile syndromes complicating paclitaxel therapy have been attributed to polyethoxylated castor oil (Kolliphor EL: BASF, Ludwigshafen, Germany), the biologic solvent included in the drug's original formulation (Taxol: Bristol-Myers Squibb, Montreal, QC), rather than the parent chemotherapy molecule. Here, we report a characteristic case of drug-induced scle complicating treatment with nanoparticle albumin bound (nab)-paclitaxel (Abraxane: Celgene, Summit, NJ, U.S.A.), a solvent-free taxane formulation. The pertinent English-language literature is also discussed. This case report is the first to link solvent-free paclitaxel with scle, and it suggests that the parent molecule is responsible for the reaction.

  16. Drug-induced long QT syndrome increases the risk of drowning.

    Science.gov (United States)

    Vincenzi, Frank F

    2016-02-01

    There is strong evidence linking inherited long QT syndromes with an increased risk of drowning due to fatal arrhythmias in the water. Drug-induced long QT syndrome (DILQTS) is hypothesized to increase the risk of drowning by similar mechanisms. It is suggested that QT prolongation caused by a drug or drugs, when combined with the autonomic conflict associated with the mammalian dive reflex and/or the cold shock reflex, sets up conditions that may result in a sudden fatal arrhythmia while in water - thus an increased risk of drowning related to a drug-induced prolongation of the QT interval. Many widely used drugs prolong the QT interval thus raising a drug safety issue that needs confirmation or refutation.

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

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    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.

  18. 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.

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

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    Behnam Behnoush

    2012-05-01

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

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

    OpenAIRE

    Ruchi Banthia; Santosh Gupta; Priyank Banthia; Pallavi Singh; Sapna Raje; Navkiran Kaur

    2014-01-01

    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 pati...

  1. Proteomics Investigations of Drug-Induced Hepatotoxicity in HepG2 Cells

    OpenAIRE

    Van Summeren, Anke; Renes, Johan; Bouwman, Freek G.; Noben, Jean-Paul; van Delft, Joost H. M.; Kleinjans, Jos C.S.; Mariman, Edwin C. M.

    2011-01-01

    Unexpected hepatotoxicity is one of the major reasons of drugs failing in clinical trials. This emphasizes the need for new screening methods that address toxicological hazards early in the drug discovery process. Here, proteomics techniques were used to gain further insight into the mechanistic processes of the hepatotoxic compounds. Drug-induced hepatotoxicity is mainly divided in hepatic steatosis, cholestasis, or necrosis. For each class, a compound was selected, respectively amiodarone, ...

  2. Interdisciplinary management of a patient with a drug-induced gingival hyperplasia

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    Raghu Devanna

    2010-01-01

    Full Text Available Interdisciplinary treatment is becoming an ever-increasing part of modern-day orthodontic practice. This case report details the successful orthodontic-periodontal management of an epileptic patient with a significant drug-induced gingival hyperplasia. The problems that such patient′s present are discussed before considering the specific orthodontic techniques employed. Recommendations are made for practitioners managing such cases.

  3. Effects of driver behavior style differences and individual differences on driver sleepiness detection

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    Keyong Li

    2015-04-01

    Full Text Available Driving sleepiness is still a major causes of traffic accidents. Individual drivers, under various conditions, act and respond in different manners. This article presents the attempt of a straight-line driving simulator study that examined the effects of driver behavior style differences and individual differences on driver sleepiness detection which is based on driving performance measures. A total of 15 drivers who were classified into two categories through subjective assessment based on a Driver Behavior Questionnaire participated in driving simulator experiments. A total of 18 detection models, including 15 SE models for each subject, an A model for the aggressive drivers, an NA model for the non-aggressive drivers, and a G model for all experiment participants, were developed using support vector machine method based on driving performance characteristic parameters. The results show that the G model is not suitable for all drivers due to its lower mean accuracy of 69.88% (standard deviation = 7.70% and higher standard deviation. The SE models for each subject show the best detection accuracy performance of 84.26% (standard deviation = 5.38%; however, it is impossible to set up a special detection model for every individual driver. The SD models on different style categories show an accuracy value of 77.54% (standard deviation = 5.78%. The results demonstrate that driver style differences as well as individual differences have great effects on driver sleepiness detection (F = 19.148, p < 0.000.

  4. Clinical analysis of 275 cases of acute drug-induced liver disease

    Institute of Scientific and Technical Information of China (English)

    LI Lei; JIANG Wei; WANG Jiyao

    2007-01-01

    In order to analyze the causative drugs,clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease,from January 2000 to December 2005,275 cases diagnosed as acute druginduced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed.Each was determined by drug history,clinical symptoms and signs,laboratory tests and therapeutic effects.In 41 cases,the diagnosis was confirmed by liver biopsy.The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased.The most common drugs which induced acute liver injuries were traditional Chinese herb medicine (23.3 %,64/275 cases),antineoplastics (15.3%,42/275),hormones and other immunosuppressant agents (13.8%,38/275),antihypertensive drugs and other cardiovascular drugs (10.2 %,28/275),NSAIDs (8.7%,24/275) respectively.Hepatocellular injury was the predominant type in these cases (132 cases,48%).The principal clinical manifestation included nausea (54.8%),fatigue (50.2%),jaundice (35.6%).27.9% patients were asymptomatic.Most patients were cured with good prognosis.The total effective rate was 94.2% after treatment.The clinicians should pay attention to the prevention,diagnosis and therapy of drug-induced liver disease.

  5. 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.

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

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    Reza Heidari

    2015-03-01

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

  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.

  8. 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

  9. Tissue distribution profiles of three antiparkinsonian alkaloids from Piper longum L. in rats determined by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liu, Haolong; Luo, Rong; Chen, Xiaoqing; Liu, Junhui; Bi, Ying; Zheng, Li; Wu, Xia

    2013-06-01

    The alkaloids of Piper longum L. (PLA) improved motor dysfunction and dopamine depletion in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. A rapid, accurate, simple, and high-performance liquid chromatography-mass spectrometry method was developed and fully validated to simultaneously detect three P. longum L. antiparkinsonian alkaloids (piperine (PPR), piperlonguminine (PPL), and Δα,β-dihydropiperlonguminine (DPPL)) in rat plasma, heart, liver, spleen, lung, kidney, and brain tissues. Rat plasma and tissue homogenates were pretreated with methanol/acetonitrile (1:1, v/v) using a simple protein precipitation method. Chromatographic separation was achieved on a Phenomenex Gemini C18 column (50mm×2.00mm, 5μm) with a gradient mobile phase containing 0.1% (v/v) formic acid in water or acetonitrile. The elution was pumped at a flow rate of 0.4ml/min, and the injection volume was 10μl with a total running time of 4min. The analysis was performed by selected reaction monitoring of the transitions m/z 285.9→201.1, m/z 274.3→209.9, and m/z 276.2→134.9 for PPR, PPL, and DPPL, respectively. All three analytes showed good linearity (R>0.995) in plasma and tissue homogenates, and the lower limit of quantification was 0.20ng/ml. The distribution of PPR, PPL and DPPL in all 7 tissues was examined. The highest concentrations for PPR and PPL were observed in the liver, while the highest DPPL concentration was observed in the kidney. Following oral administration, the highest levels of PPR, PPL and DPPL in different tissues were found at approximately 2h. PPR, PPL and DPPL could cross the blood-brain barrier. The present study provides evidences for that PPR, PPL and DPPL may play roles in improving motor dysfunction and dopamine depletion.

  10. Popular media and 'excessive daytime sleepiness': a study of rhetorical authority in medical sociology.

    Science.gov (United States)

    Kroll-Smith, Steve

    2003-09-01

    Problem sleepiness is emerging as a medical problem in the US and Britain. Though an increasingly salient complaint, clinical medicine is only peripherally involved in the diagnosis and treatment of sleep troubles. Paramount in shaping public perceptions and experiences of sleep are the popular media. The apparent chasm between self-reported sleep troubles and the routine medical gaze is the point of departure for this inquiry. Aided by the idea of rhetorical authority, a case is made for the conspicuous influence of newspapers, magazines and the Internet in shaping a persuasive cultural directive to become conscious of soporific states and their possible deleterious consequences. Attending to this cultural directive, a growing number of people are self-diagnosing with a novel sleep disorder, excessive daytime sleepiness. The increasing significance of popular culture in the creation of medical troubles summons an alternative version of medical sociology. A limited case for this claim is made by revisiting two key ideas in this field: naming diseases and the classic distinction between illness and disease.

  11. [Commuting accidents: the influence of excessive daytime sleepiness. A review of an Italian Police officers population].

    Science.gov (United States)

    Garbarino, S; Repice, A M; Traversa, F; Spigno, F; Mascialino, B; Mantineo, G; Ferrillo, F; Bonsignore, A D

    2007-01-01

    Commuting accidents (CA) play an important role in many systems of workers' compensation insurance and with good reason, as they generally bring about more serious consequences in terms of permanent disablement and death than ordinary occupational accidents; this usually leads to high social costs. Nevertheless, research investigations aimed at studying the possible causes underlying the phenomenon are not available in medical literature. Objective of the present study is to evaluate whether excessive daytime sleepiness (EDS) might influence the occurrence of CA. 463 CA occurred to 411 police officers in northern Italy during the period 1999 - 2002 were collected; 51.9% of the subjects were working on shifts, 48.1% were non-shift workers. The study was carried out by submitting a self-administered questionnaire to gather information on age and physical characteristics, working conditions, sleep-related problems and accidents occurrence; EDS was measured by the Epworth Sleepiness Scale (ESS). A large number of workers (36%) complained of EDS; a strict significant relationship between shift - work condition and the presence of EDS was found, thus suggesting that CA are significantly influenced by EDS. The shift work schedule adopted by Italian Police might be accountable for the disruption of the balance between circadian and homeostatic factors.

  12. Repeated sessions of transcranial direct current stimulation evaluation on fatigue and daytime sleepiness in Parkinson's disease.

    Science.gov (United States)

    Forogh, Bijan; Rafiei, Maryam; Arbabi, Amin; Motamed, Mohammad Reza; Madani, Seyed Pezhman; Sajadi, Simin

    2017-02-01

    Parkinson is a common and disabling disease that affects patient's and career's quality of life. Unfortunately, medications, such as dopaminergic and sedative-hypnotic drugs, as an effective treatment have unwilling side effects. Recently, Transcranial Direct Current Stimulation (tDCS) in conjunction with medication becomes popular as a complementary safe treatment and several studies have proved its effectiveness on controlling motor and specially non-motor aspects of Parkinson's disease. In this randomized double-blind parallel study, 23 patients with Parkinson's disease divided into two groups of real tDCS plus occupational therapy and sham tDCS plus occupational therapy and the effects of therapeutic sessions (eight sessions tDCS with 0.06 mA/cm(2) current, 20 min on dorsolateral prefrontal cortex) were evaluated on fatigue and daytime sleepiness just after therapeutic course and in 3-month follow-up. tDCS had a significant effect on fatigue and no effect on daytime sleepiness reduction in patients with Parkinson's disease. tDCS is an effective and safe complementary treatment on fatigue reduction in Parkinson's disease.

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

    Directory of Open Access Journals (Sweden)

    Bliwise Donald L

    2003-11-01

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

  14. Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Non-Sleepy Obstructive Sleep Apnea : The RICCADSA Randomized Controlled Trial

    NARCIS (Netherlands)

    Peker, Yüksel; Glantz, Helena; Eulenburg, Christine; Wegscheider, Karl; Herlitz, Johan; Thunström, Erik

    2016-01-01

    RATIONALE: Obstructive sleep apnea is common in patients with coronary artery disease, many of whom do not report daytime sleepiness. First-line treatment for symptomatic obstructive sleep apnea is continuous positive airway pressure, but its value in patients without daytime sleepiness is uncertain

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

    Science.gov (United States)

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

    2014-08-01

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

  16. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

    Science.gov (United States)

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J

    2014-04-27

    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

  19. Drug-induced interstitial lung diseases%药源性间质性肺疾病

    Institute of Scientific and Technical Information of China (English)

    王晓芳; 张运剑; 夏国光

    2012-01-01

    Drug-induced interstitial lung disease is the most common type of drug-induced respiratory diseases. It is known that a lot of drugs can cause interstitial lung diseases. The underlying mechanism may be associated with allergy and the direct cellular toxicity. Its clinical symptoms, imaging, and histopathology were untypical. Clinical diagnosis of the disease was based on the medical history ( medication history), clinical features, chest imaging, hi sto pathological changes, and response to treatment. If interstitial lung diseases were suspected to be; drug-induced, the drug should be discontinued immediately and glucocorticoid could be given. The prognosis is good if intervention is rapid.%药源性间质性肺疾病(DI-ILD)是最常见的药源性肺部疾病,目前已知多种药物可导致间质性肺疾病,其发病机制与药物引起的变态反应和直接细胞毒性作用有关.此类疾病临床症状、影像学及组织病理学表现均无特异性,临床诊断DI-ILD需根据病史(用药史)、临床特点、胸部影像学、组织病理学改变及治疗效果.临床疑诊DI-ILD时应立刻停药并应用糖皮质激素.若及时干预,预后良好.

  20. 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.

  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. Subjective cognitive dysfunction associated with drug-induced parkinsonism in schizophrenia.

    Science.gov (United States)

    Kim, Jong-Hoon; Kim, Seong-Youn; Byun, Hee-Jung

    2008-01-01

    The authors investigated the subjective cognitive dysfunction associated with drug-induced parkinsonism (DIP) among 58 stabilized schizophrenic outpatients. Subjective cognitive dysfunction was comprehensively assessed using the Frankfurt Complaint Questionnaire (FCQ). Multivariate analysis revealed that the DIP group scored significantly higher on the total FCQ score than the non-DIP group. In phenomenological subscale scores, the DIP group had significantly higher scores on "deterioration of discrimination", "psychomotor disorder", and "perceptual disorder" than the non-DIP group. These results suggest that DIP is significantly associated with subjective cognitive-perceptual dysfunction, reflecting the complex nature of DIP that includes motor and cognitive aspects.

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

    Directory of Open Access Journals (Sweden)

    Anup K Das

    2014-01-01

    Full Text Available 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. Treatment with diazepam of children with drug-induced extrapyramidal symptoms.

    Science.gov (United States)

    Rainier-Pope, C R

    1979-03-03

    Thirteen patients with acute dystonia and extrapyramidal symptoms as a result of drug intoxication are reported. In a number of instances, the symptoms were due to more than one drug being given to the patient, among which were phenothiazine derivatives, non-phenothiazine tranquilizers and metoclopramide. Diazepam (Valium) given intravenously caused the patients to fall asleep immediately and to wake within an hour, free from all symptoms. It is felt that in patients with drug-induced extrapyramidal symptoms, diazepam should be considered as the possible drug of choice.

  5. 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.

  6. Pharmaco-epidemiological, clinical and laboratory characteristics of drug-induced liver injury in tuberculosis

    Directory of Open Access Journals (Sweden)

    M. V. Koroleva

    2015-01-01

    Full Text Available Objective: improving the efficiency of pharmacotherapy of drug-induced liver injury in tuberculosis by clarifying pharmaco-epidemiological, clinical and laboratory features.Materials and Methods: A retrospective analysis of primary medical records of 250 patients with pulmonary tuberculosis, patients «Volgograd Regional Clinical TB Dispensary № 1». We evaluated the dynamics of biochemical parameters characterizing the development of hepatic cytolytic syndrome, examined the impact of gender and age on the incidence of liver damage, we investigated the relationship of clinical tuberculosis and chemotherapy regimen with the incidence of drug-induced liver injury, examined the clinical manifestations of liver disease.Results: Drug-induced liver injury as a complication of a specific anti-TB treatment was diagnosed in 67 patients (26,8%. In 170 patients (68,0% showed increase in alanine aminotransferase and asparaginaminotrasferazy. Hepatotoxicity significantly more common in patients with disseminated tuberculosis with the collapse of the lung tissue, smear, and a high degree of disease severity. Risk factors for drug liver damage were female gender and age older than 50 years. Women develop liver disease at an earlier date, and displays it harder than men. The earliest and most informative routine biochemical tests, reflecting the state of the liver in the dynamics are ALT and AST. It was found that the mode of the standard anti-TB treatment determines the type of liver injury: the first, 2a and 3rd modes prevails cytolytic hepatocellular type, with 2b mode – combined (mixed type 4th – type of cholestatic liver damage. It was found that repeated, after the development of hepatotoxic reactions, the appointment of anti-TB drugs without gepatoprotektsii in 94% of patients leads to repeated drug-induced liver damage. Cancel specific therapy against the background of cytolytic syndrome promotes the formation of

  7. A Novel SCN5A Mutation Associated with Drug Induced Brugada Type ECG

    OpenAIRE

    Isik, Turker; Takeru, Makiyama; Matteo, Vatta; Hideki, Itoh; Takeshi, Ueyama; Akihiko, Shimizu; Tomohiko, Ai; Minoru, Horie

    2016-01-01

    Background: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. Objective: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. Methods: Administration of pilsicainide, a class IC antiarrhythmic agent, caused ...

  8. Drug-induced immune hemolytic anemia associated with albumin-bound paclitaxel.

    Science.gov (United States)

    Thomas, Roby; Shillingburg, Alexandra

    2015-08-01

    Drug-induced immune hemolytic anemia (DIIHA) is rare, with only 1 patient in 1 million affected by the condition.1 Garratty identified 125 drugs indicated in DIIHA of which 11% were antineoplastic agents, and neither paclitaxel nor albumin-bound paclitaxel were included.2 In addition, we did not find any reports in our own search of the literature. Taxanes are known to cause anemia as a result of their myelosuppressive effects, but an immune hemolysis is rare. To our knowledge, we present here the first case of DIIHA with nab-paclitaxel.

  9. Mechanism of drug-induced gingival overgrowth revisited: a unifying hypothesis

    Science.gov (United States)

    Brown, RS; Arany, PR

    2015-01-01

    Drug-induced gingival overgrowth (DIGO) is a disfiguring side effect of anti-convulsants, calcineurin inhibitors, and calcium channel blocking agents. A unifying hypothesis has been constructed which begins with cation flux inhibition induced by all three of these drug categories. Decreased cation influx of folic acid active transport within gingival fibroblasts leads to decreased cellular folate uptake, which in turn leads to changes in matrix metalloproteinases metabolism and the failure to activate collagenase. Decreased availability of activated collagenase results in decreased degradation of accumulated connective tissue which presents as DIGO. Studies supporting this hypothesis are discussed. PMID:24893951

  10. 药源性血栓栓塞症%Drug-induced thromboembolism

    Institute of Scientific and Technical Information of China (English)

    杨文君; 徐翔

    2014-01-01

    药源性血栓栓塞症是指因某些药物使血管内血栓形成和/或栓塞并导致组织和器官功能受损的疾病.药源性血栓栓塞症的发病机制主要为血管内皮细胞损伤、血液成分改变和血流动力学异常.导致血栓栓塞症的常见药物有造影剂、化疗药、免疫抑制剂、免疫增强剂、环氧化酶2抑制剂、抗精神病药和激素等.药源性血栓栓塞症以门静脉、脾静脉、肾静脉或脑静脉窦等深静脉血栓形成较常见,动脉血栓较为少见.药源性血栓栓塞症可应用普通肝素、低分子肝素、磺达肝癸钠、华法林、尿激酶、阿替普酶、阿加曲班、重组水蛭素或达那肝素钠治疗.%The term of drug-induced thromboembolism refers to intravascular thrombosis and/or thromboembolism due to drugs and resulting in impaired tissue and organ function.The main mechanisms of drug-induced thromboembolism involve injury of endothelial cells,the change of blood components and hemodynamic abnormality.Drugs which cause thrombosis mainly include contrast media,chemotherapeutic agents,immunosuppressive agents,immunopotentiators,cyclooxygenase-2 inhibitors,antipsychotic agents,and hormones.The most common drug-induced thrombosis is deep vein thrombosis such as portal vein,splenic vein,renal vein,or cerebral venous sinus.Arterial thrombosis is less common.Drug-induced thrombosis could be treated with unfractionated heparin,low molecular weight heparin,fondaparinux sodium,warfarin,urokinase,alteplase,argatroban,recombinant hirudin or danaparoid sodium.

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

    OpenAIRE

    Komada Y; Takaesu Y; Matsui K.; Nakamura M; Nishida S; Kanno M; Usui A; Inoue Y

    2016-01-01

    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 me...

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

    Directory of Open Access Journals (Sweden)

    Amie C Hayley

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

  13. Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson's Disease?

    Science.gov (United States)

    Horváth, Krisztina; Aschermann, Zsuzsanna; Acs, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Janszky, József; Faludi, Béla; Késmárki, Ildikó; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Klivényi, Péter; Dibó, György; Vécsei, László; Takáts, Annamária; Tóth, Adrián; Imre, Piroska; Nagy, Ferenc; Herceg, Mihály; Kamondi, Anita; Hidasi, Eszter; Kovács, Norbert

    2014-01-01

    Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman's rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin's Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the "disturbed sleep" domain of PDSS-2 showed high correlation with "sleep problems" item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with "daytime sleepiness" item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation.

  14. Attention following traumatic brain injury: Neuropsychological and driving simulator data, and association with sleep, sleepiness, and fatigue.

    Science.gov (United States)

    Beaulieu-Bonneau, Simon; Fortier-Brochu, Émilie; Ivers, Hans; Morin, Charles M

    2017-03-01

    The objectives of this study were to compare individuals with traumatic brain injury (TBI) and healthy controls on neuropsychological tests of attention and driving simulation performance, and explore their relationships with participants' characteristics, sleep, sleepiness, and fatigue. Participants were 22 adults with moderate or severe TBI (time since injury ≥ one year) and 22 matched controls. They completed three neuropsychological tests of attention, a driving simulator task, night-time polysomnographic recordings, and subjective ratings of sleepiness and fatigue. Results showed that participants with TBI exhibited poorer performance compared to controls on measures tapping speed of information processing and sustained attention, but not on selective attention measures. On the driving simulator task, a greater variability of the vehicle lateral position was observed in the TBI group. Poorer performance on specific subsets of neuropsychological variables was associated with poorer sleep continuity in the TBI group, and with a greater increase in subjective sleepiness in both groups. No significant relationship was found between cognitive performance and fatigue. These findings add to the existing evidence that speed of information processing is still impaired several years after moderate to severe TBI. Sustained attention could also be compromised. Attention seems to be associated with sleep continuity and daytime sleepiness; this interaction needs to be explored further.

  15. 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.

  16. 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 g

  17. 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 g

  18. The Toronto Hospital Alertness Test scale: relationship to daytime sleepiness, fatigue, and symptoms of depression and anxiety

    Directory of Open Access Journals (Sweden)

    Shahid A

    2016-01-01

    Full Text Available Azmeh Shahid,1–5 Sharon A Chung,1,2,5 Lance Maresky,1 Affan Danish,1 Arina Bingeliene,1,4,5 Jianhua Shen,1 Colin M Shapiro1–5 1Sleep Research Laboratory, Department of Psychiatry, University Health Network, University of Toronto, 2Youthdale Treatment Centres, 3Youthdale Child and Adolescent Sleep Centre, 4Department of Psychiatry, University of Toronto, 5Department of Psychiatry, Toronto Western Hospital, University Health Network, Toronto, ON, Canada Objective: The Toronto Hospital Alertness Test (THAT scale was designed to measure alertness, defined as the capacity of the mind to respond appropriately to external and internal stimuli. The present study’s aim is to determine normative values of alertness on the THAT and to explore the relationship among excessive daytime sleepiness, fatigue, depressive symptoms, and alertness. Methods: Normative data were collected from 60 healthy males and females. To explore the relationship among alertness, daytime sleepiness, fatigue, depression, and anxiety, data were collected from charts of sleep clinic patients. All study subjects completed measures for fatigue, sleepiness, depressive symptoms, and anxiety. Results: The average score on the THAT was 34.9±7.2 (range 22–50 for the control group. The cutoff score for the THAT, indicative of clinically significant reduced alertness, was determined to be ≤20.5 (mean –2 SD. THAT alertness scores were found to be modestly, significantly, and negatively correlated with fatigue levels (r=–0.39, P<0.001, depressive symptoms (r=–0.53, P<0.001, and anxiety symptoms (r=–0.41, P<0.001. No correlations were found between alertness levels and daytime sleepiness. Regression analyses revealed a significant model (F=19.9, P<0.001, adjusted R2=0.35 with depressive symptoms (P<0.001 and fatigue (P=0.006 emerging as the only significant predictors of scores on the THAT. Conclusion: The findings of this study support that sleepiness is not the same as

  19. Daytime Sleepiness Is Associated With Reduced Integration of Temporally Distant Outcomes on the Iowa Gambling Task.

    Science.gov (United States)

    Olson, Elizabeth A; Weber, Mareen; Rauch, Scott L; Killgore, William D S

    2016-01-01

    Sleep deprivation is associated with performance decrements on some measures of executive functioning. For instance, sleep deprivation results in altered decision making on the Iowa Gambling Task. However, it is unclear which component processes of the task may be driving the effect. In this study, Iowa Gambling task performance was decomposed using the Expectancy-Valence model. Recent sleep debt and greater daytime sleepiness were associated with higher scores on the updating parameter, which reflects the extent to which recent experiences are emphasized over remote ones. Findings suggest that the effects of insufficient sleep on IGT performance are due to shortening of the time horizon over which decisions are integrated. These findings may have clinical implications in that individuals with sleep problems may not integrate more temporally distant information when making decisions.

  20. 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.

  1. 药源性自身免疫性疾病%Drug-induced Autoimmunity

    Institute of Scientific and Technical Information of China (English)

    李洪波; 林玲

    2016-01-01

    自从1945年首次报道磺胺嘧啶引起狼疮样症状至今,越来越多的药物被报道能影响人体免疫系统从而诱发自身免疫性疾病,药源性自身免疫性疾病(drug-induced autoimmunity, DIA)的关注度越来越高,但目前DIA的致病机制尚未完全阐明,尚未制定一个合适的诊断标准,治疗和预防也缺乏系统的循证医学证据。本文就 DIA的一般临床特征、致病机制、实验室检查特点、诊断、预防和治疗进行综合。%Since sulfadiazine associated lupus-like symptoms were first described in 1945, more and more drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases ( named drug-induced autoimmunity, DIA ) . However, the pathogenesis of DIA has not been fully clarified, and the standardized criteria for DIA diagnosis has not been established, and it is also lack of systematic research on its treatment and prevention. In this review, we summarize the clinical features, pathogenesis, laboratory findings, diagnosis, prevention and treatment of DIA.

  2. [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.

  3. 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.

  4. Biochemical mechanisms in drug-induced liver injury: Certainties and doubts

    Institute of Scientific and Technical Information of China (English)

    Ignazio Grattagliano; Leonilde Bonfrate; Catia V Diogo; Helen H Wang; David QH Wang; Piero Portincasa

    2009-01-01

    Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local O_2 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca~(2+)-dependent ATPase, reduced capability to sequester Ca~(2+) within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.

  5. 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

    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 AND RESU......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...... 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...... 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...

  6. Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

    Science.gov (United States)

    Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W

    2004-01-01

    The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

  7. Ready for takeoff? A critical review of armodafinil and modafinil for the treatment of sleepiness associated with jet lag.

    Science.gov (United States)

    McCarty, David E

    2010-01-01

    Jet lag syndrome (JLS) is a clinical syndrome of disrupted nocturnal sleep and daytime neurocognitive impairment which occurs in the context of rapid transmeridian travel. Many strategies for treatment of JLS exist, and include hypnotics to enhance nocturnal sleep, chronotherapeutic approaches (eg, light therapy, melatonin, or gradual schedule shifting), and alerting agents to counter daytime sleepiness. Safety concerns have prompted renewed interest in managing JLS-associated excessive daytime sleepiness (JLSAEDS). Off-label use of the newer alerting agents modafinil and armodafinil is increasing for this indication, often at the specific request of patients. In order to better evaluate the potential risks and benefits of these medications for the management of JLSAEDS, clinicians must be aware of what is known - and still not known. In this article, the pharmacology and pharmacokinetics of modafinil and armodafinil are reviewed, along with evidence for their efficacy in treating sleepiness associated with narcolepsy, obstructive sleep apnea and shift work sleep disorder. Clinical trial data for use of alerting agents in the management of JLSAEDS are limited to one three-day trial involving armodafinil, dosed in the morning to treat JLSAEDS in the setting of eastbound transmeridian travel. This study showed improvement in objective measures of daytime sleepiness at doses of 50 and 150 mg per day. However, global impression of clinical severity of symptom scores only improved on day 1 for those patients receiving 150 mg, and were otherwise not superior to placebo. Consideration for the use of modafinil or armodafinil for the treatment of sleepiness associated with JLS involves careful integration of patient-reported goals, a review of medical contraindications, and an awareness of rare adverse events. More research is needed in order to identify those who are most likely to benefit from this intervention and better define the risk-benefit ratio for this indication.

  8. 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

  9. Drug-induced liver injury: Advances in mechanistic understanding that will inform risk management.

    Science.gov (United States)

    Mosedale, M; Watkins, P B

    2016-11-09

    Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However, the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie most hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis. However, in some cases hepatocyte stress promotes an immune response that results in clinically important idiosyncratic DILI. This review discusses recent advances in our understanding of the pathogenesis of both intrinsic and idiosyncratic DILI as well as emerging tools and techniques that will likely improve DILI risk identification and management.

  10. 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.

  11. Drug-induced mitochondrial neuropathy in children: a conceptual framework for critical windows of development.

    Science.gov (United States)

    Wallace, Kendall B

    2014-09-01

    Mitochondrial disease arises from genetic or nongenetic events that interfere either directly or indirectly with the bioenergetic function of the mitochondrion and manifest clinically in some form of metabolic disorder. In primary mitochondrial disease, the critical molecular target is one or more of the individual subunits of the respiratory complexes or their assembly and incorporation into the inner mitochondrial membrane, whereas with secondary mitochondrial disease the bioenergetic deficits are secondary to effects on targets other than the electron transport chain and oxidative phosphorylation. Primary genetic events include mutations to or altered expression of proteins targeted to the mitochondrial compartment, whether they are encoded by the nuclear or mitochondrial genome. In this review, we emphasize the occurrence of nongenetic mitochondrial disease resulting from therapeutic drug administration, review the broad scope of drugs implicated in affecting specific primary mitochondrial targets, and describe evidence demonstrating critical windows of risk for the developing neonate to drug-induced mitochondrial disease and neuropathy.

  12. Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic.

    Science.gov (United States)

    Moreno, Luís; Sánchez-Delgado, Jordi; Vergara, Mercedes; Casas, Meritxell; Miquel, Mireia; Dalmau, Blai

    2015-12-01

    Ciprofloxacin and amoxicillin/clavulanic are two widely used antibiotics due to their high efficacy and few side effects. While the percentage of hepatotoxicity of these antibiotics is low, their frequent use has led to a progressive increase in the number of cases. Both antibiotics have been associated with a wide variety of hepatotoxic reactions, from a slight rise of transaminases to fulminant hepatitis. Once hepatotoxicity secondary to a drug appears, the first step is to discontinue the drug. Physicians may opt to administer an alternative treatment with a different chemical structure. It should be borne in mind, however, that different chemical structures may also cause recurrent drug-induced liver injuries (DILI). We present the case of a patient who consecutively developed DILI due to ciprofloxacin and amoxicillin/clavulanic.

  13. 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.

  14. Drug-Induced Liver Injury Network Causality Assessment: Criteria and Experience in the United States

    Directory of Open Access Journals (Sweden)

    Paul H. Hayashi

    2016-02-01

    Full Text Available Hepatotoxicity due to drugs, herbal or dietary supplements remains largely a clinical diagnosis based on meticulous history taking and exclusion of other causes of liver injury. In 2004, the U.S. Drug-Induced Liver Injury Network (DILIN was created under the auspices of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases with the aims of establishing a large registry of cases for clinical, epidemiological and mechanistic study. From inception, the DILIN has used an expert opinion process that incorporates consensus amongst three different DILIN hepatologists assigned to each case. It is the most well-established, well-described and vigorous expert opinion process for DILI to date, and yet it is an imperfect standard. This review will discuss the DILIN expert opinion process, its strengths and weaknesses, psychometric performance and future.

  15. 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

  16. Nucleoside drugs induce cellular differentiation by caspase-dependent degradation of stem cell factors.

    Directory of Open Access Journals (Sweden)

    Tanja Musch

    Full Text Available BACKGROUND: Stem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells are thus of major importance for cancer therapy. Differentiation therapy by nucleoside drugs represents an attractive approach for the elimination of cancer stem cells. However, even if it is generally assumed that the activity of these drugs is mediated by their ability to modulate epigenetic pathways, their precise mode of action remains to be established. We therefore analysed the potential of three nucleoside analogues to induce differentiation of the embryonic cancer stem cell line NTERA 2 D1 and compared their effect to the natural ligand retinoic acid. METHODOLOGY/PRINCIPAL FINDINGS: All nucleoside analogues analyzed, but not retinoic acid, triggered proteolytic degradation of the Polycomb group protein EZH2. Two of them, 3-Deazaneplanocin A (DZNep and 2'-deoxy-5-azacytidine (decitabine, also induced a decrease in global DNA methylation. Nevertheless, only decitabine and 1beta-arabinofuranosylcytosine (cytarabine effectively triggered neuronal differentiation of NT2 cells. We show that drug-induced differentiation, in contrast to retinoic acid induction, is caused by caspase activation, which mediates depletion of the stem cell factors NANOG and OCT4. Consistent with this observation, protein degradation and differentiation could be counteracted by co-treatment with caspase inhibitors or by depletion of CASPASE-3 and CASPASE-7 through dsRNA interference. In agreement with this, OCT4 was found to be a direct in-vitro-target of CASPASE-7. CONCLUSIONS/SIGNIFICANCE: We show that drug-induced differentiation is not a consequence of pharmacologic epigenetic modulation, but is induced by the degradation of stem-cell-specific proteins by caspases. Our results thus uncover a novel pathway that induces differentiation of embryonic cancer stem cells and is triggered by

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Tejas K Patel

    2014-01-01

    Full Text Available 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 drugs.

  19. Drug-Induced Liver Injury Is a Major Risk for New Drugs.

    Science.gov (United States)

    Seeff, Leonard B

    2015-01-01

    Drug-induced liver injury (DILI), a relatively rare condition, is nevertheless a major reason for not approving a drug in development or for removing one already marketed. With a specific diagnostic biomarker lacking, finding elevated serum enzyme [alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase] activities remains an initial signal for incipient liver injury. Enzyme elevations alone may not be harmful, but if caused by a drug and followed by jaundice (called 'Hy's law') there is a high possibility of serious DILI. In 1997 several drugs were approved by the Food and Drug Administration (FDA) of the USA that were later withdrawn from the market for serious liver toxicity. New drugs in development are now required to be monitored for liver injury, and the data is to be considered in the approval decision. A program called e-DISH (evaluation of drug-induced serious hepatotoxicity) was introduced in 2004 to aid medical reviewers to select from all subjects studied those few who show nontrivial liver injury and estimate the most likely cause. The threshold of enzyme elevation comprising a warning for possibly serious DILI is uncertain, although generally accepted as 3-5 times the 'upper limit of normal'. The new direct-acting antiviral agents for treating chronic hepatitis C virus, which often lead to a reduction of elevated ALTs, mandate that a later increase without viral breakthrough be compared to the new on-treatment level of values. The drug may be discontinued or interrupted for evaluation to exclude other possible causes of liver injury. The FDA has approved no drug since 1997 that has been withdrawn later because of serious hepatotoxicity.

  20. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

    Institute of Scientific and Technical Information of China (English)

    Raúl J Andrade; Mercedes Robles; Alejandra Fernández-Casta(n)er; Susana López-Ortega; M Carmen López-Vega; M Isabel Lucena

    2007-01-01

    Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice.To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

  1. Association between Screen Viewing Duration and Sleep Duration, Sleep Quality, and Excessive Daytime Sleepiness among Adolescents in Hong Kong

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    Yim Wah Mak

    2014-10-01

    Full Text Available Screen viewing is considered to have adverse impacts on the sleep of adolescents. Although there has been a considerable amount of research on the association between screen viewing and sleep, most studies have focused on specific types of screen viewing devices such as televisions and computers. The present study investigated the duration with which currently prevalent screen viewing devices (including televisions, personal computers, mobile phones, and portable video devices are viewed in relation to sleep duration, sleep quality, and daytime sleepiness among Hong Kong adolescents (N = 762. Television and computer viewing remain prevalent, but were not correlated with sleep variables. Mobile phone viewing was correlated with all sleep variables, while portable video device viewing was shown to be correlated only with daytime sleepiness. The results demonstrated a trend of increase in the prevalence and types of screen viewing and their effects on the sleep patterns of adolescents.

  2. Association between screen viewing duration and sleep duration, sleep quality, and excessive daytime sleepiness among adolescents in Hong Kong.

    Science.gov (United States)

    Mak, Yim Wah; Wu, Cynthia Sau Ting; Hui, Donna Wing Shun; Lam, Siu Ping; Tse, Hei Yin; Yu, Wing Yan; Wong, Ho Ting

    2014-10-28

    Screen viewing is considered to have adverse impacts on the sleep of adolescents. Although there has been a considerable amount of research on the association between screen viewing and sleep, most studies have focused on specific types of screen viewing devices such as televisions and computers. The present study investigated the duration with which currently prevalent screen viewing devices (including televisions, personal computers, mobile phones, and portable video devices) are viewed in relation to sleep duration, sleep quality, and daytime sleepiness among Hong Kong adolescents (N = 762). Television and computer viewing remain prevalent, but were not correlated with sleep variables. Mobile phone viewing was correlated with all sleep variables, while portable video device viewing was shown to be correlated only with daytime sleepiness. The results demonstrated a trend of increase in the prevalence and types of screen viewing and their effects on the sleep patterns of adolescents.

  3. Associations between night work and anxiety, depression, insomnia, sleepiness and fatigue in a sample of Norwegian nurses.

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    Nicolas M F Øyane

    Full Text Available BACKGROUND: Night work has been reported to be associated with various mental disorders and complaints. We investigated relationships between night work and anxiety, depression, insomnia, sleepiness and fatigue among Norwegian nurses. METHODS: The study design was cross-sectional, based on validated self-assessment questionnaires. A total of 5400 nurses were invited to participate in a health survey through the Norwegian Nurses' Organization, whereof 2059 agreed to participate (response rate 38.1%. Nurses completed a questionnaire containing items on demographic variables (gender, age, years of experience as a nurse, marital status and children living at home, work schedule, anxiety/depression (Hospital Anxiety and Depression Scale, insomnia (Bergen Insomnia Scale, sleepiness (Epworth Sleepiness Scale and fatigue (Fatigue Questionnaire. They were also asked to report number of night shifts in the last 12 months (NNL. First, the parameters were compared between nurses i never working nights, ii currently working nights, and iii previously working nights, using binary logistic regression analyses. Subsequently, a cumulative approach was used investigating associations between NNL with the continuous scores on the same dependent variables in hierarchical multiple regression analyses. RESULTS: Nurses with current night work were more often categorized with insomnia (OR = 1.48, 95% CI = 1.10-1.99 and chronic fatigue (OR = 1.78, 95% CI = 1.02-3.11 than nurses with no night work experience. Previous night work experience was also associated with insomnia (OR = 1.45, 95% CI = 1.04-2.02. NNL was not associated with any parameters in the regression analyses. CONCLUSION: Nurses with current or previous night work reported more insomnia than nurses without any night work experience, and current night work was also associated with chronic fatigue. Anxiety, depression and sleepiness were not associated with night work, and no cumulative effect of night shifts

  4. Epworth Sleepiness Scale- a novel tool to assess somnolence syndrome in patients receiving radiotherapy to the brain

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    Ritika Rajkumar Harjani

    2015-03-01

    Full Text Available Purpose: Radiation to brain causes early, early-delayed, and delayed side effects. There is paucity of literature regarding early-delayed effects like somnolence syndrome. Existing studies use general symptom assessment and visual analog scales. Epworth Sleepiness Scale (ESS is a time tested tool to assess daytime sleepiness in various conditions. In this study, the ESS has been used to determine the occurrence of somnolence in patients receiving cranial radiotherapy for primary and metastatic brain tumors. Thus the ESS has been used in a novel setting in our study. The ESS is a simple to administer questionnaire and may be useful in grading the severity of somnolence. To our knowledge, this is the second study to determine post radiation somnolence using ESS. Methods: This prospective study was conducted in 23 patients with primary and metastatic brain tumor. Patient demographics and tumor type and grade was noted. Those with Karnofsky Performance Scale (KPS less than 70 and with pre-existing sleep disorders were excluded. Radiotherapy regimen included palliative whole brain radiation for brain metastases and conformal adjuvant radiotherapy for primary brain tumors as per standard guidelines. All subjects included were administered ESS at baseline and weekly thereafter during and for 6 weeks after radiation. Results: All 23 patients (median age 50 years completed the planned questionnaires until 6 weeks post radiation. Twenty (87% patients had primary brain tumors whereas three (13% patients had metastatic lesions in brain. Of the 23 patients, 14 patients (60.86% had abnormal or increased daytime sleepiness; of which 3 had ESS scores greater than 16. Conclusion: Somnolence was noted in 60.86% of the patients, which is in accordance with existing literature. Epworth sleepiness scale is an effective tool to detect and quantify somnolence, However, it does not consider other symptoms of somnolence syndrome and hence should be combined with visual

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

    Science.gov (United States)

    Jun, Nuri; Lee, Aeri; Baik, Inkyung

    2017-01-01

    The present study investigated caffeinated beverage consumption and screen time in the association with excessive daytime sleepiness (EDS) and sleep duration. We conducted a cross-sectional study including 249 Korean male high school students. These participants responded to a questionnaire inquiring the information on lifestyle factors, consumption of caffeinated beverages, time spent for screen media, and sleep duration as well as to the Epworth Sleepiness Scale (ESS) questionnaire. EDS was defined as ESS scores of 9 or greater. Students with EDS consumed greater amount of chocolate/cocoa drinks and spent longer time for a TV and a mobile phone than those without EDS (p students with short sleep (≤ 6 hours) consumed greater amount of coffee than others whereas students with long sleep (> 8 hours) consumed greater amount of chocolate/cocoa drinks than others (p < 0.05). Screen time did not differ according to the categories of sleep duration. Although these findings do not support causal relationships, they suggest that screen time is associated with EDS, but not with sleep duration, and that consumption of certain types of caffeinated beverages is associated with EDS and sleep duration. Adolescents may need to reduce screen time and caffeine consumption to improve sleep quality and avoid daytime sleepiness.

  6. A Clinical-EEG Study of Sleepiness and Psychological Symptoms in Pharmacoresistant Epilepsy Patients Treated with Lacosamide

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    Filippo S. Giorgi

    2013-01-01

    Full Text Available Our aim was to evaluate the EEG and clinical modifications induced by the new antiepileptic drug lacosamide (LCM in patients with epilepsy. We evaluated 10 patients affected by focal pharmacoresistant epilepsy in which LCM (mean 250 mg/day was added to the preexisting antiepileptic therapy, which was left unmodified. Morning waking EEG recording was performed before (t0 and at 6 months (t1 after starting LCM. At t0 and t1, patients were also administered questionnaires evaluating mood, anxiety, sleep, sleepiness, and fatigue (Beck Depression Inventory; State-Trait Anxiety Inventory Y1 and Y2; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Fatigue Severity Scale. We performed a quantitative analysis of EEG interictal abnormalities and background EEG power spectrum analysis. LCM as an add-on did not significantly affect anxiety, depression, sleepiness, sleep quality, and fatigue scales. Similarly, adding LCM to preexisting therapy did not modify significantly patient EEGs in terms of absolute power, relative power, mean frequency, and interictal abnormalities occurrence. In conclusion, in this small cohort of patients, we confirmed that LCM as an add-on does not affect subjective parameters which play a role, among others, in therapy tolerability, and our clinical impression was further supported by evaluation of EEG spectral analysis.

  7. Excessive Daytime Sleepiness among Hypertensive US-Born Blacks and Foreign-Born Blacks: Analysis of the CAATCH Data

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    N. Williams

    2013-01-01

    Full Text Available Background. Evidence shows that blacks exhibit greater daytime sleepiness compared with whites, based on the Epworth Sleepiness Scale. In addition, sleep complaints might differ based on individuals’ country of origin. However, it is not clear whether individuals’ country of origin has any influence on excessive daytime sleepiness (EDS. Study Objectives. We tested the hypothesis that US-born blacks would show a greater level of EDS compared with foreign-born blacks. The potential effects of sociodemographic and medical risk were also determined. Design. We used the Counseling African-Americans to Control Hypertension (CAATCH data. CAATCH is a group randomized clinical trial that was conducted among 30 community healthcare centers in New York, yielding baseline data for 1,058 hypertensive black patients. Results. Results of univariate logistic regression analysis indicated that US-born blacks were nearly twice as likely as their foreign-born black counterparts to exhibit EDS (OR=1.87, 95% CI: 1.30–2.68, P<0.001. After adjusting for effects of age, sex, education, employment, body mass index, alcohol consumption, and smoking habit, US-born blacks were 69% more likely than their counterparts to exhibit EDS (OR=1.69, 95% CI: 1.11–2.57, P<0.01. Conclusion. Findings demonstrate the importance of considering individuals’ country of origin, in addition to their race and ethnicity, when analyzing epidemiologic sleep data.

  8. Are there differences in students' school success, biorhythm, and daytime sleepiness depending on their school starting times?

    Science.gov (United States)

    Milić, Jakov; Kvolik, Ana; Ivković, Martina; Cikes, Ana Babić; Labak, Irena; Benšic, Mirta; Ilakovac, Vesna; Zibar, Lada; Heffer, Marija

    2014-09-01

    Chronotype is a characteristic of a person in a certain point of one's lifetime and it slowly changes with age. Adolescents start to go to bed later while schools impose early starting hours, which may become a problem for students who are unable to adapt their circadian rhythm. The aim of this study was to determine if differences in school starting times affect the students' chronotype, school success, or daytime sleepiness. We tested a total of 1020 students from four high schools in Osijek, Croatia. The students had alternating school shifts (school starting hours 7 AM or 13 PM and 8 AM or 14 PM, every other week, alternatively, respectively). The participants were tested using the Epworth Sleepiness Scale and the Morningness--Eveningness Questionnaire. Earlier chronotypes were characteristic of the students starting school earlier, but without significant difference in daytime sleepiness in comparison with those starting school later. Differences were also found between different age and gender groups, female and older students having earlier chronotypes. Students going to school earlier showed better school success than the latter. In conclusion, the study shows that students starting school earlier also have earlier chronotypes, which might be consequence of the adaptation to one hour earlier school starting time.

  9. The Epworth Sleepiness Scale in the Assessment of Sleep Disturbance in Veterans with Tinnitus

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    Yuan F. Liu

    2015-01-01

    Full Text Available Purpose. Tinnitus and sleep disturbance are prevalent in veterans, and a better understanding of their relationship can help with tinnitus treatment. Materials and Methods. Retrospective chart review of 94 veterans seen in audiology clinic between 2010 and 2013 is presented. Results. The mean age was 62 years, and 93 of 94 veterans were males. The majority (96% had hearing loss. The positive predictive value of the ESS for sleep disorder was 97% and the negative predictive value was 100%. Veterans with a Tinnitus Handicap Inventory (THI score ≥38 had significantly higher Epworth Sleepiness Scale (ESS scores compared to those with THI score <38 (P=0.006. The former had a significantly higher incidence of PTSD, anxiety, and sleep disorder. A subgroup of patients had normal sleep despite rising THI scores. Bilateral tinnitus, vertigo, and anxiety were found to be predictors of sleep disturbance. Conclusions. The ESS can be used as a tool in the initial assessment of sleep disorders in veterans with tinnitus. Higher tinnitus handicap severity is significantly associated with greater sleep disturbance. Optimal management of tinnitus may require concomitant treatment of sleep disorder, PTSD, anxiety, and depression.

  10. 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

  11. 药源性青光眼的防治%Prevention & treatment of drug-induced glaucoma

    Institute of Scientific and Technical Information of China (English)

    马红利; 李世洋

    2015-01-01

    药源性青光眼系局部或全身用药而诱发的继发性开角或闭角青光眼。为提高临床医师对该病的认识,注意药物的不良反应,预防药源性青光眼的发生,本文就临床上可能诱发该病的常见药物、作用机制及防治作了综述。%Drug-induced glaucoma include secondary open-angle glaucoma or angle-closure glaucoma which were induced by patient's administering drugs locally or systematisally. In order to enhance physician's understanding this eye disease,and notice them to pay attention to the adverse-reaction of drugs,so that prevent drug-induced glaucoma occurence,authors review the related issures about common drugs inducing glaucoma,their action mechanism,as well as the prevention & treatment of drug-induced glaucoma in this paper.

  12. 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

  13. 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

  14. Periodic Lateralized Epileptiform Discharges can Survive Anesthesia and Result in Asymmetric Drug-induced Burst Suppression

    Science.gov (United States)

    Mader, Edward C.; Cannizzaro, Louis A.; Williams, Frank J.; Lalan, Saurabh; Olejniczak, Piotr W.

    2017-01-01

    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. PMID:28286626

  15. 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.

  16. Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System

    Institute of Scientific and Technical Information of China (English)

    Zhao Wu; Jijun Chen; Jiangtao Ren; Lei Bao; Jing Liao; Chun Cui; Linjun Rao; Hui Li; Yijun Gu; Huiming Dai; Hui Zhu; Xiaokun Teng; Lu Cheng; Lei Xiao

    2009-01-01

    Domesticated ungulate pluripotent embryonic stem (ES) cell lines would be useful for generating precise gene-modified animals. To date, many efforts have been made to establish domesticated ungulate pluripotent ES cells from early embryos without success.Here, we report the generation of porcine-induced pluripotent stem (iPS) cells using drug-inducible expression of defined factors.We showed that porcine iPS cells expressed alkaline phosphatase, SSEA3, SSEA4, Tra-1-60, Tra-1-81, Oct3/4, Nanog, Sox2, Rex1 and CDH1. Pig iPS cells expressed high levels of telomerase activity and showed normal karyotypes. These cells could differentiate into cell types of all three germ layers in vitro and in teratomas. Our study reveals properties of porcine pluripotent stem cells that may facilitate the eventual establishment of porcine ES cells. Moreover, the porcine iPS cells produced may be directly useful for the generation of precise gene-modified pigs.

  17. 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.

  18. Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

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    Salom Emery

    2012-08-01

    Full Text Available Abstract Background This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK could predict the best therapy for patients with ovarian cancer. Methods A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival were compared to the drug-induced apoptosis observed in the assay. Results Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p  Conclusion The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

  19. Drug-induced sleep endoscopy changes snoring management plan very significantly compared to standard clinical evaluation.

    Science.gov (United States)

    Pilaete, Karen; De Medts, Joris; Delsupehe, Kathelijne Godelieve

    2014-05-01

    Drug-induced sleep endoscopy (DISE) is a new tool in the work-up of patients with sleep-disordered breathing (SDB). We assessed the impact of DISE on the treatment plan of snoring patients. This is a single institution prospective longitudinal clinical trial. The setting is a private teaching hospital. A consecutive series of 100 snoring patients prospectively underwent a standardised questionnaire, clinical examination, rhinomanometry, allergy skin prick testing, DISE and polysomnography. Management plan before and after DISE evaluation was compared. In 61 patients (excluding 16 patients sent for continuous positive airway pressure, three patients refused sleep endoscopy and 20 were lost to follow-up), we compared the treatment plans. DISE showed single level airway collapse in 13 and multilevel collapse in 48 patients. The site of flutter did not add additional information as compared to the pattern and the location of the collapse. After DISE, the initial management plan changed in 41% of patients irrespective of the type of initial management plan. The only somewhat accurate initial treatment plan was uvulopalatopharyngoplasty (unchanged in 11/13 patients). Excluding moderate to severe obstructive sleep apnea patients DISE is an indispensable tool in treatment decision in all SDB patients. We suggest to simplify the protocol for DISE reporting.

  20. The role of drug-induced sleep endoscopy in surgical planning for obstructive sleep apnea syndrome.

    Science.gov (United States)

    Aktas, Ozturk; Erdur, Omer; Cirik, Ahmet Adnan; Kayhan, Fatma Tulin

    2015-08-01

    This study investigated the role of drug-induced sleep endoscopy (DISE) in the surgical treatment planning of patients with obstructive sleep apnea syndrome (OSAS). This study was conducted using patients diagnosed with OSAS between January 2007 and March 2009, who were scheduled for surgical treatment. DISE was performed using propofol in patients considered to have upper respiratory tract obstruction as indicated by Muller's maneuver. After completing the sleep endoscopy, the patient was intubated and surgery was performed (tonsillectomy and uvulopalatopharyngoplasty). A successful operation was defined as a decrease in the respiratory disturbance index to below 5 or a decrease of ≥50 % following the operation. The study included 20 patients (4 female and 16 male) aged 19-57 years. No statistically significant correlation between modified Mallampati class and operation success or between the polysomnographic stage of disease and operation success was identified. A significantly high operation success rate was found in the group with obstruction of the upper airway according to DISE (p DISE (p DISE may be used to identify the localization of obstruction for diagnostic purposes, and it can be helpful in selecting the treatment method.

  1. Drug-induced sleep endoscopy in the obstructive sleep apnea: comparison between NOHL and VOTE classifications.

    Science.gov (United States)

    da Cunha Viana, Alonço; Mendes, Daniella Leitão; de Andrade Lemes, Lucas Neves; Thuler, Luiz Claudio Santos; Neves, Denise Duprat; de Araújo-Melo, Maria Helena

    2017-02-01

    Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete collapse of the pharynx that result in a decrease in oxyhemoglobin saturation. Nasofibrolaryngoscopy under induced sleep is a promising alternative for identifying sites of upper airway obstruction in patients with OSA. This study aimed to compare the obstruction sites screened by drug-induced sleep endoscopy (DISE) using the Nose oropharynx hypopharynx and larynx (NOHL) and Velum oropharynx tongue base epiglottis (VOTE) classifications. We also determined the relationship between OSA severity and the number of obstruction sites and compared the minimum SaO2 levels between DISE and polysomnography (PSG). This was a prospective study in 45 patients with moderate and severe OSA using DISE with target-controlled infusion of propofol bispectral index (BIS) monitoring. The retropalatal region was the most frequent obstruction site, followed by the retrolingual region. Forty-two percent of patients had obstruction in the epiglottis. Concentrically shaped obstructions were more prevalent in both ratings. The relationship between OSA severity and number of obstruction sites was significant for the VOTE classification. Similar minimum SaO2 values were observed in DISE and PSG. The VOTE classification was more comprehensive in the analysis of the epiglottis and pharynx by DISE and the relationship between OSA severity and number of affected sites was also established by VOTE. The use of BIS associated with DISE is a reliable tool for the assessment of OSA patients.

  2. Drug-Induced Sleep Endoscopy Changes the Treatment Concept in Patients with Obstructive Sleep Apnoea.

    Science.gov (United States)

    Hybášková, Jaroslava; Jor, Ondřej; Novák, Vilém; Zeleník, Karol; Matoušek, Petr; Komínek, Pavel

    2016-01-01

    The present study evaluated whether drug-induced sleep endoscopy (DISE) helps identify the site of obstruction in patients with obstructive sleep apnoea (OSA). A total of 51 consecutive patients with polysomnography-confirmed OSA were enrolled in this prospective study. The presumed site of obstruction was determined according to history, otorhinolaryngologic examination, and polysomnography and a therapeutic plan designed before DISE. In 11 patients with severe OSA and/or previously failed continuous positive airway pressure (CPAP) treatment, DISE with simultaneous CPAP was performed. Multilevel collapse was noted in 49 patients (96.1%). The most frequent multilevel collapse was palatal, oropharyngeal, and tongue base collapse (n = 17, 33.3%), followed by palatal and oropharyngeal collapse (n = 12, 23.5%). Pathology of the larynx (epiglottis) was observed in 16 patients (31.4%). The laryngeal obstruction as a reason for intolerance of CPAP was observed in 3/11 (27.3%) patients. After DISE, the surgical plan was changed in 31 patients (60.8%). The results indicate that DISE helps identify the site of obstruction in the upper airways in patients with OSA more accurately and that the larynx plays an important role in OSA.

  3. Ice water submersion for rapid cooling in severe drug-induced hyperthermia

    Science.gov (United States)

    Laskowski, Larissa K.; Landry, Adaira; Vassallo, Susi U.; Hoffman, Robert S.

    2015-01-01

    Context The optimal method of cooling hyperthermic patients is controversial. Although controlled data support ice water submersion, many authorities recommend a mist and fan technique. We report two patients with drug-induced hyperthermia, to demonstrate the rapid cooing rates of ice water submersion. Case details Case 1. A 27-year-old man presented with a sympathomimetic toxic syndrome and a core temperature of 41.4°C after ingesting 4-fluoroamphetamine. He was submerged in ice water and his core temperature fell to 38°C within 18 minutes (a mean cooling rate of 0.18°C/min). His vital signs stabilized, his mental status improved and he left on hospital day 2. Case 2. A 32-year-old man with a sympathomimetic toxic syndrome after cocaine use was transported in a body bag and arrived with a core temperature of 44.4°C. He was intubated, sedated with IV benzodiazepines, and submerged in ice water. After 20 minutes his temperature fell to 38.8°C (a cooling rate of 0.28°C/min). He was extubated the following day, and discharged on day 10. Discussion In these two cases, cooling rates exceeded those reported for mist and fan technique. Since the priority in hyperthermia is rapid cooling, clinical data need to be collected to reaffirm the optimal approach. PMID:25695144

  4. Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

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    Seung Ha Lee

    2017-01-01

    Full Text Available Objective Patients with drug-induced parkinsonism (DIP may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. Methods Forty-one DIP patients were classified into normal and abnormal [18F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. Results Twenty-eight patients had normal (Group I and 13 patients had abnormal (Group II scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040. Three patients of Group I and six of Group II had hyposmia (p = 0.018. After drug withdrawal, Group I showed greater improvement in Unified Parkinson’s Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. Conclusion None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

  5. Drug-Induced Sleep Endoscopy Changes the Treatment Concept in Patients with Obstructive Sleep Apnoea

    Directory of Open Access Journals (Sweden)

    Jaroslava Hybášková

    2016-01-01

    Full Text Available The present study evaluated whether drug-induced sleep endoscopy (DISE helps identify the site of obstruction in patients with obstructive sleep apnoea (OSA. A total of 51 consecutive patients with polysomnography-confirmed OSA were enrolled in this prospective study. The presumed site of obstruction was determined according to history, otorhinolaryngologic examination, and polysomnography and a therapeutic plan designed before DISE. In 11 patients with severe OSA and/or previously failed continuous positive airway pressure (CPAP treatment, DISE with simultaneous CPAP was performed. Multilevel collapse was noted in 49 patients (96.1%. The most frequent multilevel collapse was palatal, oropharyngeal, and tongue base collapse (n=17, 33.3%, followed by palatal and oropharyngeal collapse (n=12, 23.5%. Pathology of the larynx (epiglottis was observed in 16 patients (31.4%. The laryngeal obstruction as a reason for intolerance of CPAP was observed in 3/11 (27.3% patients. After DISE, the surgical plan was changed in 31 patients (60.8%. The results indicate that DISE helps identify the site of obstruction in the upper airways in patients with OSA more accurately and that the larynx plays an important role in OSA.

  6. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Aida Ortega-Alonso

    2016-05-01

    Full Text Available Idiosyncratic drug-induced liver injury (DILI caused by xenobiotics (drugs, herbals and dietary supplements presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies.

  7. Drug-induced interstitial nephritis in a child with idiopathic nephrotic syndrome

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    Printza Nikoleta

    2009-01-01

    Full Text Available Acute renal failure (ARF is a rare but severe complication of active idiopathic nephrotic syndrome (INS in children. It may be due to several causes with different outcomes. Both the clinical picture of the patient as well as laboratory, imaging and histopathological findings may help in the diagnosis. We present a case of drug-induced acute interstitial nephritis (AIN, complicated with ARF, in a 2½ -year-old girl with active INS. The child was referred to the Hippokration General Hospital, Thessaloniki, Greece hospital with steroid-resistant NS; renal biopsy was performed, which did not show any remarkable findings and cyclosporine was admi-nistered in addition to steroid therapy. The first day after biopsy, the child developed gross hematuria and abdominal pain and an antibiotic was added to her treatment. In the following days, fever, vomiting, hypertension and ARF occurred. Ultrasound study revealed enlarged kidneys with increased echogenity and loss of corticomedullary differentiation. The antibiotic and cyclos-porine were stopped and the child was managed with furosemide, nifedipine and steroids. A second renal biopsy was performed, which confirmed the diagnosis of acute interstitial nephritis. The child did not require dialysis therapy. Her urine output improved gradually and the serum creatinine normalized one month after the initial episode. Our case re-emphasizes the need for investigation of factors precipitating ARF in children with idiopathic NS.

  8. Predicting drug-induced liver injury in human with Naïve Bayes classifier approach

    Science.gov (United States)

    Zhang, Hui; Ding, Lan; Zou, Yi; Hu, Shui-Qing; Huang, Hai-Guo; Kong, Wei-Bao; Zhang, Ji

    2016-10-01

    Drug-induced liver injury (DILI) is one of the major safety concerns in drug development. Although various toxicological studies assessing DILI risk have been developed, these methods were not sufficient in predicting DILI in humans. Thus, developing new tools and approaches to better predict DILI risk in humans has become an important and urgent task. In this study, we aimed to develop a computational model for assessment of the DILI risk with using a larger scale human dataset and Naïve Bayes classifier. The established Naïve Bayes prediction model was evaluated by 5-fold cross validation and an external test set. For the training set, the overall prediction accuracy of the 5-fold cross validation was 94.0 %. The sensitivity, specificity, positive predictive value and negative predictive value were 97.1, 89.2, 93.5 and 95.1 %, respectively. The test set with the concordance of 72.6 %, sensitivity of 72.5 %, specificity of 72.7 %, positive predictive value of 80.4 %, negative predictive value of 63.2 %. Furthermore, some important molecular descriptors related to DILI risk and some toxic/non-toxic fragments were identified. Thus, we hope the prediction model established here would be employed for the assessment of human DILI risk, and the obtained molecular descriptors and substructures should be taken into consideration in the design of new candidate compounds to help medicinal chemists rationally select the chemicals with the best prospects to be effective and safe.

  9. 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.

  10. Rare Occurrence of Drug Induced Subacute Cutaneous Lupus Erythematosus with Leflunomide Therapy.

    Science.gov (United States)

    Singh, Harpreet; Sukhija, Gagandeep; Tanwar, Vikram; Arora, Sameer; Bhutani, Jaikrit

    2016-10-01

    Leflunomide is an immunomodulatory drug exhibiting anti-inflammatory, anti-proliferative and immunosuppressive effects. It has been widely used for treatment of active rheumatoid arthritis. Despite its good safety profile cutaneous side effects like alopecia, eczema, pruritis and dry skin have been reported with Leflunomide use. Skin ucleration, vasculitis, lichenoid drug rash and Subacute Cutaneous Lupus Erythematosus (SCLE) have been rarely reported with its use. A rare case of Leflunomide induced SCLE is being reported in a female patient with rheumatoid arthritis. The clinical features, histopathological and immunological characteristics were consistent with drug induced SCLE. Withdrawal of Leflunomide along with short course of topical steroids resulted in resolution of symptoms suggesting the drug to be the culprit. As this drug comes into widespread use, it remains to be seen whether more cases of DI-SCLE will occur/be reported. Fortunately, such a condition till times appears rare and is reversible once the drug is discontinued thus avoiding over evaluation and over treatment if the triggering drug is recognized.

  11. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Nasser M

    2013-09-01

    Full Text Available Mohammad Nasser, Timothy R Larsen, Barryton Waanbah, Ibrahim Sidiqi, Peter A McCullough Providence Hospitals and Medical Centers, Department of Medicine, Division of Cardiology, Southfield and Novi, MI, USA Abstract: Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient’s acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion. Keywords: intravenous amiodarone, acute hepatotoxicity, liver transaminases, drug-induced liver toxicity

  12. Simple and sensitive method for monitoring drug-induced cell injury in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Shirhatti, V.; Krishna, G.

    1985-06-01

    A simple, sensitive method has been developed for evaluating cell injury noninvasively in monolayer cells in culture. The cell ATP pool was radiolabeled by incubating the cells with (/sup 14/C)adenine. The uptake and incorporation of (/sup 14/C)adenine was shown to proportional to the number of cells. As determined by HPLC, about 65-70% of the incorporated /sup 14/C label was in the ATP pool, 15-20% was in the ADP pool, and the rest was in the 5'-AMP pool. When prelabeled cells were exposed to toxic drugs (acetaminophen, calcium ionophore A-23187, or daunomycin) there was a marked decrease in cell ATP with a concomitant increase in leakage of labeled nucleotides, mainly 5'-AMP and 5'IMP. The authors have shown that leakage of /sup 14/C label into the medium from the prelabeled cells may be employed for quantitation of cell injury. This new measure of toxicity was shown to correlate very well with LDH leakage from the cells, which is a well accepted measure of cell injury. The leakage of 5'-(/sup 14/C)AMP also correlated very well with the reduction of cell ATP in cardiac myocytes. This method has been used for monitoring drug-induced toxicity in liver cells, cardiac myocytes, and LB cells.

  13. Drug-Induced Sleep Endoscopy Changes the Treatment Concept in Patients with Obstructive Sleep Apnoea

    Science.gov (United States)

    Jor, Ondřej; Novák, Vilém; Matoušek, Petr

    2016-01-01

    The present study evaluated whether drug-induced sleep endoscopy (DISE) helps identify the site of obstruction in patients with obstructive sleep apnoea (OSA). A total of 51 consecutive patients with polysomnography-confirmed OSA were enrolled in this prospective study. The presumed site of obstruction was determined according to history, otorhinolaryngologic examination, and polysomnography and a therapeutic plan designed before DISE. In 11 patients with severe OSA and/or previously failed continuous positive airway pressure (CPAP) treatment, DISE with simultaneous CPAP was performed. Multilevel collapse was noted in 49 patients (96.1%). The most frequent multilevel collapse was palatal, oropharyngeal, and tongue base collapse (n = 17, 33.3%), followed by palatal and oropharyngeal collapse (n = 12, 23.5%). Pathology of the larynx (epiglottis) was observed in 16 patients (31.4%). The laryngeal obstruction as a reason for intolerance of CPAP was observed in 3/11 (27.3%) patients. After DISE, the surgical plan was changed in 31 patients (60.8%). The results indicate that DISE helps identify the site of obstruction in the upper airways in patients with OSA more accurately and that the larynx plays an important role in OSA. PMID:28070516

  14. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi

    2011-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  15. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

    Science.gov (United States)

    Lin, Christine

    2016-01-01

    Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans. PMID:27725933

  16. The role of eNOS phosphorylation in causing drug-induced vascular injury.

    Science.gov (United States)

    Tobin, Grainne A McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; González, Carlos; Bancos, Simona; Zhang, Leshuai; Lawton, Michael P; Enerson, Bradley E; Weaver, James L

    2014-06-01

    Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.

  17. Drug induced liver injury: do we still need a routine liver biopsy for diagnosis today?

    Science.gov (United States)

    Teschke, Rolf; Frenzel, Christian

    For the pathologist, the diagnosis of drug induced liver injury (DILI) is challenging, because histopathological features mimic all primary hepatic and biliary diseases, lacking changes that are specific for DILI. Therefore, in any patient of suspected DILI who underwent liver biopsy, the pathologist will assure the clinician that the observed hepatic changes are compatible with DILI, but this information is less helpful due to lack of specificity. Rather, the pathologist should assess liver biopsies blindly, without knowledge of prior treatment by drugs. This will result in a detailed description of the histological findings, associated with suggestions for potential causes of these hepatic changes. Then, it is up to the physician to reassess carefully the differential diagnoses, if not done before. At present, liver histology is of little impact establishing the diagnosis of DILI with the required degree of certainty, and this shortcoming also applies to herb induced liver injury (HILI). To reach at the correct diagnoses of DILI and HILI, clinical and structured causality assessments are therefore better approaches than liver histology results obtained through liver biopsy, an invasive procedure with a low complication rate.

  18. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives.

    Science.gov (United States)

    Fontana, Robert J

    2014-04-01

    Idiosyncratic drug-induced liver injury (DILI) is a rare disease that develops independently of drug dose, route, or duration of administration. Furthermore, idiosyncratic DILI is not a single disease entity but rather a spectrum of rare diseases with varying clinical, histological, and laboratory features. The pathogenesis of DILI is not fully understood. Standardization of the DILI nomenclature and methods to assess causality, along with the information provided by the LiverTox Web site, will harmonize and accelerate research on DILI. Studies of new serum biomarkers such as glutamate dehydrogenase, high mobility group box protein 1, and microRNA-122 could provide information for use in diagnosis and prognosis and provide important insights into the mechanisms of the pathogenesis of DILI. Single nucleotide polymorphisms in the HLA region have been associated with idiosyncratic hepatotoxicity attributed to flucloxacillin, ximelagatran, lapatinib, and amoxicillin-clavulanate. However, genome-wide association studies of pooled cases have not associated any genetic factors with idiosyncratic DILI. Whole genome and whole exome sequencing analyses are under way to study cases of DILI attributed to a single medication. Serum proteomic, transcriptome, and metabolome as well as intestinal microbiome analyses will increase our understanding of the mechanisms of this disorder. Further improvements to in vitro and in vivo test systems should advance our understanding of the causes, risk factors, and mechanisms of idiosyncratic DILI.

  19. Antinuclear antibody-negative, drug-induced lupus caused by lisinopril.

    Science.gov (United States)

    Carter, J D; Valeriano-Marcet, J; Kanik, K S; Vasey, F B

    2001-11-01

    The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL.

  20. 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

    2015-09-09

    : 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.

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

    Directory of Open Access Journals (Sweden)

    Millena Drumond Bicalho

    2015-09-01

    Full Text Available : 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.

  2. Drug induced interstitial lung disease in oncology phase I trials.

    Science.gov (United States)

    Yonemori, Kan; Hirakawa, Akihiro; Kawachi, Asuka; Kinoshita, Fumie; Okuma, Hitomi; Nishikawa, Tadaaki; Tamura, Kenji; Fujiwara, Yasuhiro; Takebe, Naoko

    2016-12-01

    Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phase I trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade 3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4 months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phase I trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients.

  3. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity.

    Science.gov (United States)

    Beger, Richard D; Sun, Jinchun; Schnackenberg, Laura K

    2010-03-01

    Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAEs) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field.

  4. Rare Occurrence of Drug Induced Subacute Cutaneous Lupus Erythematosus with Leflunomide Therapy

    Science.gov (United States)

    Singh, Harpreet; Tanwar, Vikram; Arora, Sameer; Bhutani, Jaikrit

    2016-01-01

    Leflunomide is an immunomodulatory drug exhibiting anti-inflammatory, anti-proliferative and immunosuppressive effects. It has been widely used for treatment of active rheumatoid arthritis. Despite its good safety profile cutaneous side effects like alopecia, eczema, pruritis and dry skin have been reported with Leflunomide use. Skin ucleration, vasculitis, lichenoid drug rash and Subacute Cutaneous Lupus Erythematosus (SCLE) have been rarely reported with its use. A rare case of Leflunomide induced SCLE is being reported in a female patient with rheumatoid arthritis. The clinical features, histopathological and immunological characteristics were consistent with drug induced SCLE. Withdrawal of Leflunomide along with short course of topical steroids resulted in resolution of symptoms suggesting the drug to be the culprit. As this drug comes into widespread use, it remains to be seen whether more cases of DI-SCLE will occur/be reported. Fortunately, such a condition till times appears rare and is reversible once the drug is discontinued thus avoiding over evaluation and over treatment if the triggering drug is recognized. PMID:27891379

  5. Dynamic Drug-Induced Sleep Computed Tomography in Adults With Obstructive Sleep Apnea

    Science.gov (United States)

    Li, Hsueh-Yu; Lo, Yu-Lun; Wang, Chao-Jan; Hsin, Li-Jen; Lin, Wan-Ni; Fang, Tuan-Jen; Lee, Li-Ang

    2016-01-01

    Surgical success for obstructive sleep apnea (OSA) depends on identifying sites of obstruction in the upper airway. In this study, we investigated sites of obstruction by evaluating dynamic changes in the upper airway using drug-induced sleep computed tomography (DI-SCT) in patients with OSA. Thirty-five adult patients with OSA were prospectively enrolled. Sleep was induced with propofol under light sedation (bispectral index 70–75), and low-dose 320-detector row CT was performed for 10 seconds over a span of 2–3 respiratory cycles with supporting a continuous positive airway pressure model. Most (89%) of the patients had multi-level obstructions. Total obstruction most commonly occurred in the velum (86%), followed by the tongue (57%), oropharyngeal lateral wall (49%), and epiglottis (26%). There were two types of anterior-posterior obstruction of the soft palate, uvular (94%) and velar (6%), and three types of tongue obstruction, upper (30%), lower (37%), and upper plus lower obstruction (33%). DI-SCT is a fast and safe tool to identify simulated sleep airway obstruction in patients with OSA. It provides data on dynamic airway movement in the sagittal view which can be used to differentiate palate and tongue obstructions, and this can be helpful when planning surgery for patients with OSA. PMID:27762308

  6. 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

  7. 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

  8. Drug treatment of patients with insomnia and excessive daytime sleepiness: pharmacokinetic considerations.

    Science.gov (United States)

    Nishino, S; Mignot, E

    1999-10-01

    Insomnia and excessive daytime sleepiness (EDS) are frequently observed conditions in the general public. A national survey in the USA in 1979 indicated that 35% of American adults experience insomnia in the course of a year. The prevalence of EDS varies depending on the survey (0.3 to 13.3%), but a recent study stated that 2.4% of individuals reported that they continually fell asleep at work. These problems are often long term and negatively affect the individuals' quality of life. People with these sleep problems often have difficulties maintaining high levels of productivity at work or pursuing their daily activities; individuals with insomnia lack the feeling of being rested or refreshed in the morning and EDS is unavoidable in most cases. Behavioural therapy has been shown to be effective for many people affected with insomnia and EDS. However, pharmacological treatments using hypnosedatives and central nervous system (CNS) stimulants are usually necessary, and effective, for those with more severe cases. These compounds have thus been widely prescribed in clinical practice (e.g., 2.6% of all adults surveyed used medically prescribed hypnosedatives and 4.5% used over-the-counter drugs to promote sleep). The onset and duration of action of these hypnosedatives and CNS stimulant drugs are important factors to be considered when prescribing these compounds. These factors primarily depend on physicochemical properties (lipid solubility and protein binding), as well as the pharmacokinetic profile (absorption, distribution, elimination and clearance) of the compounds. Significant differences in profile exist amongst hypnosedatives and CNS stimulants, and these differences may account for the observed variations in clinical action and adverse effects during and after treatment. In this review, we will introduce recently obtained knowledge of the pharmacokinetics of hypnosedatives and CNS stimulants and their applications for patients affected with insomnia and EDS.

  9. Drug-induced sleep endoscopy: conventional versus target controlled infusion techniques--a randomized controlled study.

    Science.gov (United States)

    De Vito, Andrea; Agnoletti, Vanni; Berrettini, Stefano; Piraccini, Emanuele; Criscuolo, Armando; Corso, Ruggero; Campanini, Aldo; Gambale, Giorgio; Vicini, Claudio

    2011-03-01

    Understanding the sites of pharyngeal collapse is mandatory for surgical treatment decision-making in obstructive sleep-apnea-hypopnea syndrome patients. Drug-induced sleep endoscopy (DISE) allows for the direct observation of the upper airway during sedative-induced sleep. In order to re-create snoring and apnea patterns related to a spontaneous sleep situation, the authors used a target-controlled infusion (TCI) sleep endoscopy (DISE-TCI), comparing this technique to conventional DISE, in which sedation was reached by a manual bolus injection. The authors conducted a prospective, randomized, unicenter study. The apneic event observation and its correlation with pharyngeal collapse patterns is the primary endpoint; secondary endpoints are defined as stability and safety of sedation plans of DISE-TCI technique. From January 2009 to June 2009, 40 OSAHS patients were included in the study and randomized allocated in two groups: the bolus injection conventional DISE group and the DISE-TCI group. We recorded the complete apnea event at the oropharynx and hypopharynx levels in 4 patients of the conventional DISE group (20%) and in 17 patients of the DISE-TCI group (85%) (P DISE group because of severe desaturation that resulted from the first bolus of propofol (1 mg/kg) (P = 0.4872 ns). We recorded the instability of the sedation plan in 13 patients from the conventional DISE group (65%) and 1 patient from the DISE-TCI group (5%) (P = 0.0001). Our results suggest that the DISE-TCI technique should be the first choice in performing sleep endoscopy because of its increased accuracy, stability and safety.

  10. Drug induced sleep endoscopy in the decision-making process of children with obstructive sleep apnea.

    Science.gov (United States)

    Galluzzi, Francesca; Pignataro, Lorenzo; Gaini, Renato Maria; Garavello, Werner

    2015-03-01

    Tonsillectomy and adenoidectomy (T&A) is currently recommended in children with Obstructive Sleep Apnea (OSA). However, the condition persists after surgery in about one third of cases. It has been suggested that Drug Induced Sleep Endoscopy (DISE) may be of help for planning a more targeted and effective surgical treatment but evidence is yet weak. The aim of this review is to draw recommendation on the use of DISE in children with OSA. More specifically, we aimed at determine the proportion of cases whose treatment may be influenced by DISE findings. A comprehensive search of articles published from February 1983 to January 2014 listed in the PubMed/MEDLINE databases was performed. The search terms used were: "endoscopy" or "nasoendoscopy" or "DISE" and "obstructive sleep apnea" and "children" or "child" or "pediatric." The main outcome was the rate of naive children with hypertrophic tonsils and/or adenoids. The assumptions are that clinical diagnosis of hypertrophic tonsils and/or adenoids is reliable and does not require DISE, and that exclusive T&A may solve OSA in the vast majority of cases even in the presence of other concomitant sites of obstruction. Five studies were ultimately selected and all were case series. The median (range) number of studied children was 39 (15-82). Mean age varied from 3.2 to 7.8 years. The combined estimate rate of OSA consequent to hypertrophic tonsils and/or adenoids was 71% (95%CI: 64-77%). In children with Down Syndrome, the combined estimated rate of hypertrophic tonsils and/or adenoids was 62% (95%CI: 44-79%). Our findings show that DISE may be of benefit in a minority of children with OSA since up to two thirds of naive cases presents with hypertrophic tonsils and/or adenoids. Its use should be limited to those whose clinical evaluation is unremarkable or when OSA persists after T&A.

  11. Identification and management of in-hospital drug-induced delirium in older patients.

    Science.gov (United States)

    Catic, Angela G

    2011-09-01

    Delirium, an acute confusional state with changes in attention and cognition, is a common cause of morbidity and mortality among hospitalized elders. Medications are responsible for up to 39% of delirium cases in the elderly. The incidence of drug-induced delirium is particularly high in this population due to the altered pharmacokinetics and pharmacodynamics of aging, high prevalence of polypharmacy and occurrence of co-morbid disease. Although certain medications are more often associated with the development of delirium, including opioids, benzodiazepines, anticholinergics and antidepressants, any medication can cause delirium in the elderly. Evaluation of delirium should include a thorough medication history, which should determine if any new medications have been initiated, if medications have been discontinued, and the details of any recent dosage adjustments. It is important to understand the utility of medications in preventing and treating delirium in the elderly. Acetylcholinesterase inhibitors have not been found to reduce the incidence of delirium or length of hospitalization. Study results regarding the utility of antipsychotic medications in preventing delirium have been mixed. Haloperidol prophylaxis did not reduce the occurrence of delirium, but it did reduce the severity and duration. Olanzapine and risperidone were associated with a reduced incidence of delirium compared with placebo. Pharmacological therapy to treat delirium should be implemented only if patients pose a safety risk to themselves or others. Typical and atypical antipsychotics are effective in treating the symptoms of delirium, but it is important to note that they are not approved by the US FDA for this indication. Short-acting benzodiazepines are second-line therapy and are typically reserved for patients with sedative/alcohol withdrawal, Parkinson's disease or neuroleptic malignant syndrome. Study results regarding the utility of acetylcholinesterase inhibitors have been mixed.

  12. Assessing the risk of drug-induced cholestasis using unbound intrahepatic concentrations.

    Science.gov (United States)

    Riede, Julia; Poller, Birk; Huwyler, Jorg; Camenisch, Gian

    2017-03-02

    Inhibition of the bile salt export pump (BSEP) has been recognized as a key factor in the development of drug-induced cholestasis (DIC). The risk of DIC in human has previously been assessed using in vitro BSEP inhibition data (IC50) and unbound systemic drug exposure under assumption of the "free drug hypothesis". This concept, however, is unlikely valid as unbound intrahepatic drug concentrations are affected by active transport and metabolism. To investigate this hypothesis we experimentally determined the in vitro liver-to-blood partition coefficients (Kp,uu) for 18 drug compounds using the hepatic Extended Clearance Model (ECM). In vitro-in vivo translatability of Kp,uu values was verified for a subset of compounds in rat. Consequently, unbound intrahepatic concentrations were calculated from clinical exposure (systemic and hepatic inlet) and measured Kp,uu data. Using these values, corresponding safety margins against BSEP IC50 values were determined and compared to the clinical incidence of DIC. Depending on the ECM class of a drug, in vitro Kp,uu values deviated up to 14-fold from unity and unbound intrahepatic concentrations were affected accordingly. The use of in vitro Kp,uu-based safety margins allowed to separate clinical cholestasis frequency into three classes (no cholestasis, cholestasis in ≤ 2%, and in > 2% of subjects) for 17 out of 18 compounds. This assessment was significantly superior compared to using unbound extracellular concentrations as a surrogate for intrahepatic concentrations. Furthermore, the assessment of Kpuu according to ECM provides useful guidance for the quantitative evaluation of genetic and physiological risk factors for the development of cholestasis.

  13. 药源性干眼症%Drug-induced dry eye

    Institute of Scientific and Technical Information of China (English)

    杨永升; 张守康; 谢立科

    2012-01-01

    Drug-induced dry eye is gradually recognized by ophthalmologists in recent years.It has been found that more than 10 categories and hundreds of drugs can induce dry eye,which include anti-cholinergic receptor drugs,antihistamines,antidepressant drugs,anti-psychotic drugs,hormone drugs,antiglaucoma drugs,and so on.The main mechanisms include the influence of drugs on the parasympathetic/sympathetic system so that the secretion pathway of lacrimal gland blocked,or tear film instability and ocular surface abnormalities caused by eye drops or ointments. Preventions and treatments are mainly to stop or change the drugs,etiological treatment and symptomatic treatment.%药源性干眼症是近年来逐渐被认识的一类药源性眼病,引起此病的药物有十余类上百种,其中常见的有抗胆碱能受体药、抗组胺药、抗抑郁症类药、抗精神病类药、激素类药、抗青光眼类药等.主要机制是药物影响副交感或交感神经系统,支配腺体分泌的通路受到阻断;或药物局部使用引起泪膜不稳定及眼表面异常.防治此类干眼症主要采用停药或换药,对因治疗以及对症处理.

  14. 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

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

    Science.gov (United States)

    Banthia, Ruchi; Gupta, Santosh; Banthia, Priyank; Singh, Pallavi; Raje, Sapna; Kaur, Navkiran

    2014-01-01

    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 PMID:25426150

  16. 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.

  17. [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.

  18. Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

    Science.gov (United States)

    Vicente, Jose; Johannesen, Lars; Hosseini, Meisam; Mason, Jay W.; Sager, Philip T.; Pueyo, Esther; Strauss, David G.

    2016-01-01

    Background Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Thus, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the “CiPA” initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans. Methods and Results In this study we assess the ability of eight ECG morphology biomarkers to detect late sodium current block in the presence of QTc prolongation by analyzing a clinical trial where a selective hERG potassium channel blocker (dofetilide) was administered alone and then in combination with two late sodium current blockers (lidocaine and mexiletine). We demonstrate that late sodium current block has the greatest effect on the heart-rate corrected J-Tpeak interval (J-Tpeakc), followed by QTc and then T-wave flatness. Furthermore, J-Tpeakc is the only biomarker that improves detection of the presence of late sodium current block compared to using QTc alone (AUC: 0.83 vs. 0.72 respectively, p<0.001). Conclusions Analysis of the J-Tpeakc interval can differentiate drug-induced multichannel block involving the late sodium current from selective hERG potassium channel block. Future methodologies assessing drug effects on cardiac ion channel currents on the ECG should use J-Tpeakc to detect the presence of late sodium current block. Trial Registration NCT02308748 and NCT01873950 PMID:28036334

  19. The utility of a rodent model in detecting pediatric drug-induced nephrotoxicity.

    Science.gov (United States)

    Espandiari, Parvaneh; Zhang, Jun; Rosenzweig, Barry A; Vaidya, Vishal S; Sun, Jinchun; Schnackenberg, Laura; Herman, Eugene H; Knapton, Alan; Bonventre, Joseph V; Beger, Richard D; Thompson, Karol L; Hanig, Joseph

    2007-10-01

    A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg(-1) body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten- and 40-day-old rats given 100 mkd of GM for 6- or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e.g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies.

  20. 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.

  1. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Science.gov (United States)

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

  2. Assessment of time interval between tramadol intake and seizure and second drug-induced attack

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    Bahareh Abbasi

    2015-11-01

    Full Text Available Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years were enrolled in this study. Convulsion was seen in 104 patients (69.3%. In 8 out of 104 patients (7.6% two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3% were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.

  3. The effect of split sleep schedules (6h-on/6h-off) on neurobehavioural performance, sleep and sleepiness.

    Science.gov (United States)

    Short, Michelle A; Centofanti, Stephanie; Hilditch, Cassie; Banks, Siobhan; Lushington, Kurt; Dorrian, Jillian

    2016-05-01

    Shorter, more frequent rosters, such as 6h-on/6h-off split shifts, may offer promise to sleep, subjective sleepiness and performance by limiting shift length and by offering opportunities for all workers to obtain some sleep across the biological night. However, there exists a paucity of studies that have examined these shifts using objective measures of sleep and performance. The present study examined neurobehavioural performance, sleepiness and sleep during 6h-on/6h-off split sleep schedules. Sixteen healthy adults (6 males, 26.13 y ± 4.46) participated in a 9-day laboratory study that included two baseline nights (BL, 10h time in bed (TIB), 2200 h-0800 h), 4 days on one of two types of 6h-on/6h-off split sleep schedules with 5h TIB during each 'off' period (6h early: TIB 0300 h-0800 h and 1500 h-20000 h, or 6-h late: TIB 0900 h-1400 h and 2100 h-0200 h), and two recovery nights (10h TIB per night, 2200 h-0800 h). Participants received 10h TIB per 24h in total across both shift schedules. A neurobehavioural test bout was completed every 2 h during wake, which included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS). Linear mixed effects models were used to assess the effect of day (BL, shift days 1-4), schedule (6h early, 6h late) and trial (numbers 1-6) on PVT lapses (operationalised as the number of reaction times >500 ms), PVT total lapse time, PVT fastest 10% of reaction times and KSS. Analyses were also conducted examining the effect of day and schedule on sleep variables. Overall, PVT lapses and total lapse time did not differ significantly between baseline and shift days, however, peak response speeds were significantly slower on the first shift day when compared to baseline, but only for those in the 6h-late condition. Circadian variations were apparent in performance outcomes, with individuals in the 6h-late condition demonstrated significantly more and longer lapses and slower peak reaction times at the end of their

  4. DRUG INDUCED HYPOGLYCEMIC COMA IN A NONDIABETIC WITH CHRONIC LIVER DISEASE: A CASE REPORT OF DRUG DISPENSING ERROR

    Directory of Open Access Journals (Sweden)

    Krishna M

    2014-08-01

    Full Text Available Hypoglycemia is a common, potentially fatal, yet preventable problem. Drug-induced hypoglycemia remains the commonest cause of hypoglycemia. A 63 year old non-diabetic male, a known case of chronic liver disease, on regular medications, presented with unconsciousness, unresponsiveness since two hours. Immediate random blood sugar was 11 mg/dl. On proper history and clinical examination, diagnosis of oral hypoglycemic agent induced hypoglycemic coma was made and immediately intravenous dextrose resuscitation was started. Patient regained consciousness after four hours and became fully oriented after 24 hours. Throughout his hospital course, strict and frequent glucose monitoring was done and dextrose infused accordingly. Patient remained hemodynamically stable throughout the hospital course. He was discharged from the hospital after 72 hours in an otherwise healthy condition. Drug induced hypoglycemia is now so relatively common that virtually every unconscious patient should be considered hypoglycemic until immediate estimation of the blood sugar level rules the condition in or out.

  5. A rare cause of drug-induced hepatitis in an immunocompromised patient and the role of glutathione.

    Science.gov (United States)

    Senadhi, Viplove; Arora, Deepika; Arora, Manish; Marsh, Franklin

    2012-08-27

    The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the most common outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.

  6. The role of ultrahigh-frequency audiometry in the early detection of systemic drug-induced hearing loss.

    Science.gov (United States)

    Singh Chauhan, Rajeev; Saxena, Ravinder Kumar; Varshey, Saurabh

    2011-05-01

    In monitoring patients for drug-induced hearing loss, most audiometric evaluations are limited to the range of frequencies from 0.25 to 8 kHz. However, such testing would fail to detect ototoxicity in patients who have already experienced hearing loss in the ultrahigh frequencies from 10 to 20 kHz. Awareness of ultrahigh-frequency ototoxicity could lead to changes in a drug regimen to prevent further damage. We conducted a prospective study of 105 patients who were receiving a potentially ototoxic drug-either gentamicin, amikacin, or cisplatin-to assess the value of ultrahigh-frequency audiometry in detecting systemic drug-induced hearing loss. We found that expanding audiometry into the ultrahigh-frequency range led to the detection of a substantial number of cases of hearing loss that would have otherwise been missed.

  7. Change in daytime sleepiness and cognitive function in a 6-month, double-blind study of lurasidone and quetiapine XR in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Philip D. Harvey

    2016-09-01

    Full Text Available Daytime sleepiness is a commonly reported adverse effect associated with psychotropic agents that may impair cognitive performance and functioning. The objective of this post-hoc analysis was to evaluate the long-term effects of lurasidone and quetiapine XR on daytime sleepiness and neurocognitive performance during a 6-month, double-blind continuation study, in subjects who completed an initial 6-week, randomized, placebo-controlled trial comparing these agents. Daytime sleepiness, cognitive performance, and health-related quality of life were assessed with the Epworth Sleepiness Scale (ESS, CogState computerized battery, and the Quality of Well-Being (QWB-SA Scale, respectively. Treatment with flexible-dose lurasidone 40–160 mg/d, administered once daily in the evening, was associated with significantly reduced daytime sleepiness compared with flexibly dosed quetiapine XR 200–800 mg/d (p = 0.03, effect size = 0.36 at week 32 (month 6 of the continuation study endpoint. Incidence of markedly high sleepiness (ESS >10 was significantly higher in the quetiapine XR (200–800 mg/d group compared with the lurasidone (40–160 mg/day group at both months 3 and 6 visits (p < 0.05. Lurasidone (40–160 mg/d significantly improved neurocognitive performance compared to quetiapine XR (200–800 mg/d before (effect size = 0.49 and after adjustment (effect size = 0.45 for sleepiness effect (p = 0.008 and 0.010, respectively. Increased daytime sleepiness was significantly associated with reduced neurocognitive performance (p = 0.019 and quality of well-being (p = 0.05. Our findings suggest that clinicians should actively monitor patients for the presence of daytime sleepiness due in part to its potential impact on neurocognitive performance and well-being.

  8. Sonolência diurna excessiva em trabalhadores da área de enfermagem Excessive daytime sleepiness in nursing workers

    Directory of Open Access Journals (Sweden)

    José Carlos Souza

    2007-01-01

    Full Text Available OBJETIVO: A sonolência diurna excessiva (SDE caracteriza-se por episódios de sono em situações em que o indivíduo deveria estar acordado. Objetivou-se detectar a prevalência de SDE em trabalhadores da área de enfermagem. MÉTODOS: Fez-se um estudo, descritivo e de corte transversal em 226 trabalhadores de enfermagem de um hospital público de Campo Grande, MS. Foi aplicada a Escala de Sonolência de Epworth (ESE. RESULTADOS: Foi encontrada uma prevalência de 30,09% de SDE. Não foram detectadas relações entre SDE e gênero, idade, trabalho em turnos, uso de hipnóticos; 27,64% trabalhavam em turnos fixos e 32% alternados. CONCLUSÕES: Foi alta a prevalência de SDE em trabalhadores da área de enfermagem na amostra avaliada. Sugere-se que medidas sejam tomadas para uma abordagem adequada deste transtorno neste grupo.OBJETIVE: Excessive daytime sleepiness (EDS is characterized by episodes of naps or moments of sleep in situations where the individual should be awake. The objective was to detect the prevalence of EDS in nursing professionals. METHODS: A transverse study was carried out, descriptive, in 226 workers in the nursing in a public hospital in Campo Grande, Mato Grosso do Sul. The Epworth Sleepiness Scale (ESS was applied. RESULTS: It was found a prevalence of 30,09% of sleepiness. No connection was detected in the occurrence of EDS between the sexes, ages, shift work and use of hypnotics. 27,64% worked in fixed shift and 32,00% in alternating shift. CONCLUSIONS: The prevalence of EDS manifested among nursing professionals was shown to be high. Steps should be taken to provide treatment for this disturbance.

  9. Organotypic functional cultures of human liver cells for long-term maintenance and assessment of drug-induced metabolome effects

    OpenAIRE

    MÜLLER Daniel

    2011-01-01

    The goals of this thesis were (i) to establish and improve organotypic liver cell culture techniques for long-term pharmacological studies and (ii) to develop and apply a metabolomics based approach for the assessment of drug-induced effects. As first model, a 3D bioreactor system was characterized in terms of cell physiology and functionality. Primary human hepatocytes could be kept viable and functional for more than 2 weeks in this system. Optimization of the system allowed determination o...

  10. High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device.

    Science.gov (United States)

    Kim, Min Jung; Lee, Su Chul; Pal, Sukdeb; Han, Eunyoung; Song, Joon Myong

    2011-01-07

    Drug-induced cardiotoxicity or cytotoxicity followed by cell death in cardiac muscle is one of the major concerns in drug development. Herein, we report a high-content quantitative multicolor single cell imaging tool for automatic screening of drug-induced cardiotoxicity in an intact cell. A tunable multicolor imaging system coupled with a miniaturized sample platform was destined to elucidate drug-induced cardiotoxicity via simultaneous quantitative monitoring of intracellular sodium ion concentration, potassium ion channel permeability and apoptosis/necrosis in H9c2(2-1) cell line. Cells were treated with cisapride (a human ether-à-go-go-related gene (hERG) channel blocker), digoxin (Na(+)/K(+)-pump blocker), camptothecin (anticancer agent) and a newly synthesized anti-cancer drug candidate (SH-03). Decrease in potassium channel permeability in cisapride-treated cells indicated that it can also inhibit the trafficking of the hERG channel. Digoxin treatment resulted in an increase of intracellular [Na(+)]. However, it did not affect potassium channel permeability. Camptothecin and SH-03 did not show any cytotoxic effect at normal use (≤300 nM and 10 μM, respectively). This result clearly indicates the potential of SH-03 as a new anticancer drug candidate. The developed method was also used to correlate the cell death pathway with alterations in intracellular [Na(+)]. The developed protocol can directly depict and quantitate targeted cellular responses, subsequently enabling an automated, easy to operate tool that is applicable to drug-induced cytotoxicity monitoring with special reference to next generation drug discovery screening. This multicolor imaging based system has great potential as a complementary system to the conventional patch clamp technique and flow cytometric measurement for the screening of drug cardiotoxicity.

  11. Biomarkers for metabolic drug activation : towards an integrated risk assessment for drug-induced liver injury (DILI)

    OpenAIRE

    Teppner, Marieke

    2014-01-01

    The term drug-induced liver injury (DILI) describes adverse effects upon therapeutic drug treatment. They are relatively rare, affecting only 1 of 10000 - 1000000 patients, and remain mostly unpredictable. Due to development of severe hepatotoxicity or death, drugs causing DILI display a high risk for patients and have been withdrawn from the market or severely restricted in use. For the pharmaceutical industry late stage attrition due to DILI represents a big burden stretching development ti...

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

    Directory of Open Access Journals (Sweden)

    Maria Fagerbakke Eldevik

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

  13. Are There Differences in Students’ School Success, Biorhythm, and Daytime Sleepiness Depending on Their School Starting Times?

    OpenAIRE

    Milić, Jakov; Kvolik, Ana; Ivković, Martina; Babić Čikeš, Ana; Labak, Irena; Benšić, Mirta; Ilakovac, Vesna; Ništ, Marina; Zibar, Lada; Heffer, Marija

    2014-01-01

    Chronotype is a characteristic of a person in a certain point of one’s lifetime and it slowly changes with age. Adolescents start to go to bed later while schools impose early starting hours, which may become a problem for students who are unable to adapt their circadian rhythm. The aim of this study was to determine if differences in school starting times affect the students’ chronotype, school success, or daytime sleepiness. We tested a total of 1020 students from four high schools in Osije...

  14. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs.

    Science.gov (United States)

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    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.

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

    Science.gov (United States)

    Nishiyama, Akira; Dey, Anup; Tamura, Tomohiko; Ko, Minoru; Ozato, Keiko

    2012-01-01

    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.

  16. 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.

  17. Prevention and Treatment of Vaginal Bleeding after Drug-induced Abortion by Yaoliuan Capsule and Its Effects on Menses Recovery

    Institute of Scientific and Technical Information of China (English)

    JIN Zhichun; HUANG Guangying

    2005-01-01

    Summary: 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 ≤ 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8 %) of complete 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.

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

    Science.gov (United States)

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

    2014-09-03

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

  19. ABC gene-ranking for prediction of drug-induced cholestasis in rats

    Directory of Open Access Journals (Sweden)

    Yauheniya Cherkas

    2016-01-01

    Full Text Available As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants and gene expression. In the present study, a novel “aggregating bundles of clusters” (ABC procedure was applied to separate cholestatic from non-cholestatic drugs and model toxicants in the Johnson & Johnson (Janssen rat liver toxicogenomics database [3]. Drug-induced cholestasis is an important issue, particularly when a new compound enters the market with this liability, with standard preclinical models often mispredicting this toxicity. Three well-characterized cholestasis-responsive genes (Cyp7a1, Mrp3 and Bsep were chosen from a previous in-house Janssen gene expression signature; these three genes show differing, non-redundant responses across the 90+ paradigm compounds in our database. Using the ABC procedure, extraneous contributions were minimized in comparisons of compound gene responses. All genes were assigned weights proportional to their correlations with Cyp7a1, Mrp3 and Bsep, and a resampling technique was used to derive a stable measure of compound similarity. The compounds that were known to be associated with rat cholestasis generally had small values of this measure relative to each other but also had large values of this measure relative to non-cholestatic compounds. Visualization of the data with the ABC-derived signature showed a very tight, essentially identically behaving cluster of robust human cholestatic drugs and experimental cholestatic toxicants (ethinyl estradiol, LPS, ANIT and methylene dianiline, disulfiram, naltrexone, methapyrilene, phenacetin, alpha-methyl dopa, flutamide, the NSAIDs–—indomethacin, flurbiprofen, diclofenac, flufenamic acid, sulindac, and nimesulide, butylated hydroxytoluene, piperonyl butoxide, and bromobenzene, some slightly less active compounds (3′-acetamidofluorene, amsacrine, hydralazine, tannic acid, some

  20. α1-Syntrophin Variant Identified in Drug-Induced Long QT Syndrome Increases Late Sodium Current.

    Science.gov (United States)

    Choi, Jong-Il; Wang, Chaojian; Thomas, Matthew J; Pitt, Geoffrey S

    2016-01-01

    Drug-induced long-QT syndrome (diLQTS) is often due to drug block of IKr, especially in genetically susceptible patients with subclinical mutations in the IKr-encoding KCHN2. Few variants in the cardiac NaV1.5 Na+ channel complex have been associated with diLQTS. We tested whether a novel SNTA1 (α1-syntrophin) variant (p.E409Q) found in a patient with diLQTS increases late sodium current (INa-L), thereby providing a disease mechanism. Electrophysiological studies were performed in HEK293T cells co-expressing human NaV1.5/nNOS/PMCA4b with either wild type (WT) or SNTA1 variants (A390V-previously reported in congenital LQTS; and E409Q); and in adult rat ventricular cardiomyocytes infected with SNTA1 expressing adenoviruses (WT or one of the two SNTA1 variants). In HEK293T cells and in cardiomyocytes, there was no significant difference in the peak INa densities among the SNTA1 WT and variants. However, both variants increased INa-L (% of peak current) in HEK293T cells (0.58 ± 0.10 in WT vs. 0.90 ± 0.11 in A390V, p = 0.048; vs. 0.88 ± 0.07 in E409Q, p = 0.023). In cardiomyocytes, INa-L was significantly increased by E409Q, but not by A390V compared to WT (0.49 ± 0.14 in WT vs.0.94 ± 0.23 in A390V, p = 0.099; vs. 1.12 ± 0.24 in E409Q, p = 0.019). We demonstrated that a novel SNTA1 variant is likely causative for diLQTS by augmenting INa-L. These data suggest that variants within the NaV1.5-interacting α1-syntrophin are a potential mechanism for diLQTS, thereby expanding the concept that variants within congenital LQTS loci can cause diLQTS.

  1. α1-Syntrophin Variant Identified in Drug-Induced Long QT Syndrome Increases Late Sodium Current.

    Directory of Open Access Journals (Sweden)

    Jong-Il Choi

    Full Text Available Drug-induced long-QT syndrome (diLQTS is often due to drug block of IKr, especially in genetically susceptible patients with subclinical mutations in the IKr-encoding KCHN2. Few variants in the cardiac NaV1.5 Na+ channel complex have been associated with diLQTS. We tested whether a novel SNTA1 (α1-syntrophin variant (p.E409Q found in a patient with diLQTS increases late sodium current (INa-L, thereby providing a disease mechanism. Electrophysiological studies were performed in HEK293T cells co-expressing human NaV1.5/nNOS/PMCA4b with either wild type (WT or SNTA1 variants (A390V-previously reported in congenital LQTS; and E409Q; and in adult rat ventricular cardiomyocytes infected with SNTA1 expressing adenoviruses (WT or one of the two SNTA1 variants. In HEK293T cells and in cardiomyocytes, there was no significant difference in the peak INa densities among the SNTA1 WT and variants. However, both variants increased INa-L (% of peak current in HEK293T cells (0.58 ± 0.10 in WT vs. 0.90 ± 0.11 in A390V, p = 0.048; vs. 0.88 ± 0.07 in E409Q, p = 0.023. In cardiomyocytes, INa-L was significantly increased by E409Q, but not by A390V compared to WT (0.49 ± 0.14 in WT vs.0.94 ± 0.23 in A390V, p = 0.099; vs. 1.12 ± 0.24 in E409Q, p = 0.019. We demonstrated that a novel SNTA1 variant is likely causative for diLQTS by augmenting INa-L. These data suggest that variants within the NaV1.5-interacting α1-syntrophin are a potential mechanism for diLQTS, thereby expanding the concept that variants within congenital LQTS loci can cause diLQTS.

  2. Evaluation of prognostic markers in severe drug-induced liver disease

    Institute of Scientific and Technical Information of China (English)

    Bo Li; Zhi Wang; Jian-Jiang Fang; Ci-Yi Xu; Wei-Xing Chen

    2007-01-01

    AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy's rule and the most important predictors for outcome.METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed.RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD, and 140 (52.8%) of them were female. Hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminant hepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012).CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal

  3. Selective blockade of drug-induced place preference conditioning by ACPC, a functional NDMA-receptor antagonist.

    Science.gov (United States)

    Papp, Marius; Gruca, Piotr; Willner, Paul

    2002-11-01

    ACPC (1-aminocyclopropanecarboxylic acid) is a partial agonist at the strychnine-insensitive glycine receptor site on the NMDA receptor complex, and a functional NMDA antagonist. A series of experiments was conducted to assess the effects of ACPC in a biased place conditioning paradigm. As previously reported, ACPC itself did not support either appetitive or aversive place conditioning. However, co-administration of ACPC (200 mg/kg) blocked the acquisition of place preferences conditioned using a variety of psychoactive drugs (amphetamine, cocaine, nomifensine, diazepam, morphine, nicotine). No tolerance was seen to this effect following two weeks of chronic ACPC administration. Overall, ACPC did not affect the expression of place conditioning when administered immediately before the post-conditioning test. However, these effects appeared somewhat variable between drugs, and further analysis showed that ACPC did block the expression of preferences conditioned with some drugs (diazepam, morphine, nicotine), but not others (amphetamine, cocaine, nomifensine). The effects of ACPC could not be accounted for by state dependence, as ACPC blocked morphine and cocaine place preferences when administered during both the acquisition and the expression phase of conditioning. In contrast to the blockade by ACPC of drug-induced place preferences, ACPC had no effect on the acquisition of place preferences conditioned using a variety of natural non-drug reinforcers (food, sucrose, social interaction, novelty). ACPC also had no effect on the acquisition of drug-induced place aversions (naloxone, picrotoxin). Thus, ACPC selectively blocked appetitive conditioning by drug reinforcers, without affecting either appetitive conditioning by natural reinforcers or drug-induced aversions. As place preference conditioning has been demonstrated to have high predictive validity for detecting compounds with an abuse potential in humans, this selective action suggests that ACPC might have some

  4. Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.

    Science.gov (United States)

    Goldring, Christopher; Antoine, Daniel J; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J; Hanley, Neil A; Hay, David C; Ingelman-Sundberg, Magnus; Juhila, Satu; Kitteringham, Neil; Silva-Lima, Beatriz; Norris, Alan; Pridgeon, Chris; Ross, James A; Young, Rowena Sison; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J; Zhang, Fang; Park, B Kevin

    2017-02-01

    Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721).

  5. 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.

  6. 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.

  7. 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.

  8. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease.

    Science.gov (United States)

    Pais, Raluca; Rusu, Elena; Ratziu, Vlad

    2014-02-01

    Steatosis and insulin resistance (IR) are no more frequent in chronic hepatitis B (CHB) than in the general population. Although experimental studies suggest that the HBx protein induces liver fat, human studies have shown that steatosis and IR are related to coexistent metabolic risk factors, thus epidemiologically linked rather than virally induced. Diabetes and obesity are associated with advanced fibrosis and increased risk of hepatocellular carcinoma in CHB. Despite abundant experimental data showing that fatty liver is more susceptible to liver injury, drug-induced liver disease seems no more frequent in NAFLD patients, except, possibly, a higher incidence but not severity of acetaminophen hepatotoxicity.

  9. Application of a Drug-Induced Apoptosis Assay to Identify Treatment Strategies in Recurrent or Metastatic Breast Cancer

    Science.gov (United States)

    Bosserman, Linda; Rogers, Karl; Willis, Carl; Davidson, Dirk; Whitworth, Pat; Karimi, Misagh; Upadhyaya, Gargi; Rutledge, James; Hallquist, Allan; Perree, Mathieu; Presant, Cary A.

    2015-01-01

    Background 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. Methods 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). Results 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). Conclusions 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. Trial Registration Clinicaltrials.gov NCT

  10. Parent Report and Actigraphically Defined Sleep in Children with and without Developmental Coordination Disorder; Links with Fatigue and Sleepiness

    Directory of Open Access Journals (Sweden)

    Luci Wiggs

    2016-08-01

    Full Text Available Background: Impaired sleep is associated with negative effects on quality of life and daytime functioning. Higher rates of sleep disturbance are reported in children with various developmental disorders. However, little is known about sleep in children with Developmental Coordination Disorder (DCD, a condition characterized by everyday movement difficulties. Previously, in a preliminary study, we found higher rates of parent-reported sleep disturbance in children with DCD compared to controls. Aims: To examine sleep in DCD using objective measures and to examine links with daytime fatigue and sleepiness. Methods: Two groups (primary and secondary school-aged of 15 children with DCD, plus matched controls, participated. Parent reported child sleep was assessed using the Children’s Sleep Habits Questionnaire and actigraphy provided an objective measure of sleep-wake patterns over one week (including weekdays and weekend. Pediatric Restless Legs Syndrome (RLS Semi-Structured Diagnostic Interview was conducted with each child and parent to capture symptoms of RLS. Aspects of self-rated child functioning were assessed with questionnaires (Pre-sleep Arousal Scale, Pediatric Daytime Sleepiness Scale, PedsQL Multidimensional Fatigue Scale and mothers’ reported thoughts about child sleep with the Maternal Cognitions about Infant Sleep Questionnaire.Results: The DCD groups had greater parent-reported sleep disturbance. Actigraphy results suggested that for secondary aged children with DCD their sleep quality was impaired and there were differences in the timing of sleep compared to controls (including some differences in the variation between weekday and weekend sleep times. The actigraphy of the primary age group with DCD was unremarkable compared to controls. No child in the study met the criteria for RLS. Exploratory analyses suggested that daytime fatigue, aspects of pre-sleep arousal and daytime sleepiness were reported as greater in the DCD

  11. Fonoaudiologia e apneia do sono: uma revisão Speech therapy and sleepy apnae: a review

    Directory of Open Access Journals (Sweden)

    Erilucia Pereira Santa Rosa

    2010-10-01

    Full Text Available TEMA: a Síndrome da Apneia/Hipopneia Obstrutiva do Sono (SAHOS é definida pela Academia Americana do Sono como a presença de episódios recorrentes de obstrução parcial ou total das vias aéreas superiores durante o sono e manifesta-se como uma redução (hipopneia ou cessação completa (apneia do fluxo aéreo, apesar da manutenção dos esforços inspiratórios. A SAHOS motiva o chamado ronco crônico, sonolência e caracteriza-se pela parada do fluxo aéreo respiratório por pelo menos, 10 segundos. O diagnóstico é realizado através do exame polissonográfico, que consiste no registro simultâneo de atividades do organismo durante a noite, indicando a quantidade de apneias e hipopneias ocorridos e a gravidade da SAHOS. Para sucesso no tratamento desta desordem é fundamental o diagnóstico preciso e correto e a atuação de uma equipe multidisciplinar, estando inserido nela o fonoaudiólogo. OBJETIVO: analisar, através da literatura a interrrelação da Fonoaudiologia e a SAHOS. CONCLUSÃO: aom o referente estudo, podemos identificar a complexidade da SAHOS e mostrar a importância da atuação fonoaudiológica na terapêutica desses pacientes, para uma melhor qualidade de vida.BACKGROUND: the Apnea syndrome / Obstructive Sleepy Hypopnea (SOHAS is define by the American Academy of Sleep with recurrent presence of episodes of partial or total obstruction in the superior airways during sleep, in addition to showing a reduction (hypopnea or complete stoppage (apnea of airflow, although there is an ongoing maintenance of inspiratory efforts. SOHAS motivates the so-called sleepy chronic snoring and sleepiness to dress up by the stop of airflow by at least 10 seconds. The diagnosis is carried out through polysomnographic examination, which consists of the simultaneous recording of body activities during the night, indicating the number of occurring apneas and hypopneas and SOHAS severity. For the successful of disorder treatment it is

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

    Directory of Open Access Journals (Sweden)

    Cecilia Rastad

    2011-01-01

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

  13. Scatter Plot Analysis of Excessive Daytime Sleepiness and Severe Disruptive Behavior in Adults with Prader-Willi Syndrome: A Pilot Study

    Science.gov (United States)

    Maas, Anneke P. H. M.; Didden, Robert; Bouts, Lex; Smits, Marcel G.; Curfs, Leopold M. G.

    2009-01-01

    Individuals with Prader-Willi syndrome (PWS) are at risk for excessive daytime sleepiness (EDS) and disruptive behavior. This pilot study explores temporal characteristics of EDS and severe disruptive behavior across time of day and day of week in seven individuals with PWS (aged between 33 and 49 years) of whom five were matched to controls.…

  14. Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis

    DEFF Research Database (Denmark)

    Knudsen, S; Jennum, P J; Korsholm, K

    2008-01-01

    There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system...... has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations......, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission......, in 48 consecutively referred patients with relapsing-remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 +/- 3.0) and remission (5.8 +/- 2.6), and mean CSF hcrt-1 was normal (456 +/- 41 pg...

  15. Experimental investigation of the effects of the car driver`s postures on sleepiness; Chakuza shisei ga nemuke ni oyobosu eikyo ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Komatsudani, M.; Okamura, C. [Toyo Seat Co. Ltd., Hiroshima (Japan); Nishiyama, S. [Hiroshima City Industrial Technology Institute, Hiroshima (Japan); Nozawa, T.; Nishikawa, K. [Matsuda Motor Corp., Hiroshima (Japan); Hori, T.; Hayashi, M. [Hiroshima University, Hiroshima (Japan)

    1998-05-01

    Effects of car driver`s postures on sleepiness were experimentally investigated. For the measurement method of EEG (electroencephalogram), bipolar induction was adopted, to record Cz and Pz using those at left ear as standard by international 10-20 electrode method. In addition, differential potential was recorded between locations of Cz and Pz. The time constant of EEG was set in 0.3 sec. Brain waves were measured for one minute under open and close eye conditions before and after each test as EEG at the rest. For the measurement of EOG (electro-oculograph), vertical and horizontal eye motions were observed. Induced potential change was measured by attaching silver-silver chloride electrode at the time constant 1.5 sec. For the measurement of SPL (skin potential level), the palm of left hand was used as a measuring point and the left front arm was used as a reference point for attaching electrodes. The danger of sleepiness was provided by the boring driving conditions independent of driver`s postures. There was a difference of relaxation time due to the driver`s postures. It was difficult to avoid sleepiness by adjusting the relative angle between seat and seat back. However, it was found that the angle 110deg was most suitable for avoiding sleepiness. 7 refs., 5 figs., 2 tabs.

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

    Science.gov (United States)

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

    2015-12-01

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

  17. Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Tadahiro Shinozawa

    2017-02-01

    Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

  18. 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.

  19. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

    Science.gov (United States)

    Schultz, Luise; Zurich, Marie-Gabrielle; Culot, Maxime; da Costa, Anaelle; Landry, Christophe; Bellwon, Patricia; Kristl, Theresa; Hörmann, Katrin; Ruzek, Silke; Aiche, Stephan; Reinert, Knut; Bielow, Chris; Gosselet, Fabien; Cecchelli, Romeo; Huber, Christian G; Schroeder, Olaf H-U; Gramowski-Voss, Alexandra; Weiss, Dieter G; Bal-Price, Anna

    2015-12-25

    The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Christine Bernsmeier

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

  2. Cytomorphological Effects of Mitomycin C on Urothelial Cells: Eosinophils May Be Clue to The Drug-Induced Changes

    Directory of Open Access Journals (Sweden)

    Gulcin Guler Simsek

    2014-04-01

    Full Text Available Cytomorphological changes of mitomycin C on urothelial cells may be misinterpreted as a neoplastic process. A 60-year old male patient who was given an eight-week course of intravesical mitomycin C due to non-invasive low grade transitional cell carcinoma. During his follow-up care, the findings of a urine cytology exam were as follows: nuclear enlargement of cells, wrinkled nuclear membranes, little hyperchromasia, pleomorphism, abnormal nuclear morphology and disordered orientation of the urothelium. Furthermore, there were eosinophils nearby the atypical cells. This report aimed at reminding the cytomorphologic changes of mitomycin C may be misinterpreted as carcinoma, so the presence of eosinophils is required to predict the drug-induced changes.

  3. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    DEFF Research Database (Denmark)

    Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W

    2010-01-01

    the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies....... Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human......). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results  Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats...

  4. Investigation of parameters highlighting drug induced small changes of the T-wave's morphology for drug safety studies.

    Science.gov (United States)

    Baas, Tobias; Gräfe, Ksenija; Khawaja, Antoun; Dössel, Olaf

    2011-01-01

    In guideline E14, the American Food and Drug Administration (FDA) requests for clinical studies to investigate the prolongation of the heart rate corrected QT-interval (QTc) of the ECG. As drug induced QT-prolongation can be caused by changes in the repolarisation of the ventricles, it is so far a thorough ECG biomarker of risk for ventricular tachyarrhythmias and Torsade de Pointes (TdP). Ventricular repolarisation changes not only change QT but also influence the morphology of the T-wave. In a (400 mg single dose) Moxifloxacin positive control study both, QTc and several descriptors describing the T-wave morphology have been measured. Moxifloxacin is changing two shape dependent descriptors significantly (P<0.05) about 3 to 4 hours after a 400 mg oral single dose of Moxifloxacin.

  5. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Ramesh Kumar Gupta; Ashok Kumar Gupta; Sudhansu Ranjan Swain; Vaishali; Gaurav Gupta; Saifuddin Khalid; Didagi Kulkarni Suresh; Rajnish Kumar Singh

    2013-01-01

    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 3d5r udg sin experimental animals. Liver toxicity was induced by combination of three antitubercular suspen(siisoonn ifaozr id 7.5 mg/kg, rifampicin 10 mg/kg and pyrazinamide 35 mg/kg) given orally as drugs. 35 d in rats. Treatment groups received I. carnea extracts along with antitubercular aspartaTteh ea mhienpoattroapnrsofeteracstiev,e a alacntiivniet ya mwainso atrsasnessfseerda sues, ianlgk avlainrieo upsh obsipochhaetimsei caanl dp atortaaml ebtielirrsu bliikne. dMiesmanuwtahsiele a, nind- cvaivtaol aasnet iwoxeirdea mnte aascutirveidti eisn aras t lliipviedr pheormoxoigdeantaioten ,a rloendgu cweidth g lutathione, superoxide ATPase and G-6-Pase. The biochemical observations were supplemented by histopathological examination. Results: Obtained results demonstrated that treatment with I. carnea extracts significantly h(Pedrug induced increase in serum levels of peroxidation in theF ulrivtheer rtmisosruee, Ia.n cda rrnesetao reexdt raaccttisv istiigens ifoifc adnetfleyn c(uep atnot iPox

  7. Stem cell-derived models to improve mechanistic understanding and prediction of human drug induced liver injury

    Science.gov (United States)

    Goldring, Christopher; Antoine, Daniel J.; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J.; Hanley, Neil A.; Hay, David C.; Ingelman-Sundberg, Magnus; Juhila, Satu; Kitteringham, Neil; Silva-Lima, Beatriz; Norris, Alan; Pridgeon, Chris; Ross, James A.; Sison Young, Rowena; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J.; Zhang, Fang; Park, B. Kevin

    2016-01-01

    Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalised toxicology to determine inter-individual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury (DILI) means that no current single cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human DILI. Nevertheless, a single cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment, and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally-differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. PMID:27775817

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

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

    Science.gov (United States)

    Funk, Juergen; Robbins, Justin B.; Crogan-Grundy, Candace; Presnell, Sharon C.; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    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. PMID:27387377

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.

  13. Rat granulocyte colony-forming unit (CFU-G) assay for the assessment of drug-induced hematotoxicity.

    Science.gov (United States)

    Matsumura-Takeda, K; Kotosai, K; Ozaki, A; Hara, H; Yamashita, S

    2002-06-01

    To assess the drug-induced hematotoxicity to granulocyte progenitors, we established a modified colony-forming assay using rat bone marrow cells (BMCs). In the presence of various colony-stimulating factors (CSFs), rat BMCs were disseminated on methylcellulose at a concentration of 1.3 x 10(4) cells/cm(2) (5 x 10(4) cells/0.5 ml/well in a 12-well plate). Mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) stimulated the formation of almost all macrophage colonies. Human granulocyte colony-stimulating factor (hG-CSF) alone or in combination with mouse interleukin-3 (mIL-3) did not significantly effect on the number of rat colony-forming units in culture (CFU-C). When BMCs were seeded at 5.2 x 10(4) cells/cm(2) (5 x 10(5) cells/1 ml/dish in a 35-mm dish), hG-CSF increased the number of the colonies in a dose-dependent manner, and resulted in about 50 colonies at 50 ng/ml. The constituent cells of the colonies were identified as neutrophils. Under these conditions, the effects of 5-fluorouracil (5-FU) on granulocyte colony-forming units (CFU-G) were examined in rats and mice. The inhibitory effect of 5-FU on rat CFU-G was similar to the effect on mouse CFU-G. These results indicate that the rat CFU-G induced by hG-CSF is capable of being used for the evaluation of drug-induced hematotoxicity.

  14. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Qian-Ji Ning; Shao-Wei Qin; Cun-Shuan Xu

    2006-01-01

    AIM: To study the action of the genes associated with drug-induced liver diseases at the gene transcriptional level during liver regeneration (LR) in rats.METHODS: The genes associated with drug-induced liver diseases were obtained by collecting the data from databases and literature, and the gene expression changes in the regenerating liver were checked by the Rat Genome 230 2.0 array.RESULTS: The initial and total expression numbers of genes occurring in phases of 0.5-4 h after partial hepatectomy (PH), 4-6 h after PH (G0/G1 transition),6-66 h after PH (cell proliferation), 66-168 h after PH (cell differentiation and structure-function reconstruction) were 21, 3, 9, 2 and 21, 9, 19, 18, respectively. It is illustrated that the associated genes were mainly triggered at the initial stage of LR and worked at different phases. According to their expression similarity,these genes were classified into 5 types: only upregulated (12 genes), predominantly up-regulated (4genes), only down-regulated (11 genes), predominantly down-regulated (3 genes), and approximately up-/down-regulated (2 genes). The total times of their upand down-expression were 130 and 79, respectively,demonstrating that expression of most of the genes was increased during LR, while a few decreased. The cell physiological and biochemical activities during LR were staggered according to the time relevance and were diverse and complicated in gene expression patterns.CONCLUSION: Drug metabolic capacity in regenerating liver was enhanced. Thirty-two genes play important roles during liver regeneration in rats.

  15. Drug induced linear IgA disease with unusual features: Koebner phenomenon, local insulin sensitivity and annular blister of the nipples.

    Science.gov (United States)

    Rashid Dar, Nasser; Raza, Naeem

    2008-01-01

    Linear IgA disease is an autoimmune subepidermal bullous disease in which linear IgA deposits are found at the basement membrane zone. It is classically idiopathic but may be drug induced. We report on a patient with drug induced linear IgA disease who exhibited certain unusual and interesting clinical features including isomorphic Koebner response, annular blister of the nipples and local insulin sensitivity. To the best of our knowledge, these clinical features have not yet been reported in linear IgA disease.

  16. 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.

  17. The Effect of Armodafinil on Patient-Reported Functioning and Quality of Life in Patients With Excessive Sleepiness Associated With Shift Work Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

    OpenAIRE

    Erman, Milton K.; Yang, Ronghua; Seiden, David J.

    2012-01-01

    Objective: To examine whether treatment with armodafinil for 6 weeks affected patient-reported overall functioning and daily quality of life compared with placebo in patients with excessive sleepiness associated with shift work disorder.

  18. Sleep Apnea, Sleep Debt and Daytime Sleepiness Are Independently Associated with Road Accidents. A Cross-Sectional Study on Truck Drivers

    OpenAIRE

    Garbarino, Sergio; Durando, Paolo; Guglielmi, Ottavia; Dini, Guglielmo; Bersi, Francesca; Fornarino, Stefania; Toletone, Alessandra; Chiorri, Carlo; Magnavita, Nicola

    2016-01-01

    Background Recent research has found evidence of an association between motor vehicle accidents (MVAs) or near miss accidents (NMAs), and excessive daytime sleepiness (EDS) or its main medical cause, Obstructive Sleep Apnea (OSA). However, EDS can also be due to non-medical factors, such as sleep debt (SD), which is common among professional truck drivers. On the opposite side, rest breaks and naps are known to protect against accidents. Study Objectives To investigate the association of OSA,...

  19. Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apnea

    OpenAIRE

    Roth, Thomas; Rippon, Gregory A.; Arora, Sanjay

    2007-01-01

    Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some patients with obstructive sleep apnea (OSA). A pooled analysis of two 12-week, randomized, double-blind studies in nCPAP-adherent patients with ES associated with OSA evaluated the effect of armodafinil on wakefulness and cognition. Three hundred and ninety-one patients received armodafinil (150 or 250 mg) and 260 patients received...

  20. Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"

    DEFF Research Database (Denmark)

    Linderup, Mette Werner

    Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"......Fremlæggelse af projekt med Epworth søvnighedsskema, opgørelse af data fra 2009-2014: "Prevalence of excessive daytime sleepiness in patients treated with orthognathic surgery"...

  1. The impact of daytime sleepiness on the school performance of college students with attention deficit hyperactivity disorder (ADHD): a prospective longitudinal study.

    Science.gov (United States)

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

    2014-06-01

    This prospective longitudinal study evaluated the impact of daytime sleepiness on the school performance of 62 college students diagnosed comprehensively with attention deficit hyperactivity disorder. The primary goal of the study was to determine if self-reported daytime sleepiness rated at the beginning of the academic year could predict academic and overall functioning at the end of the academic year while also considering potentially important covariates, including symptoms of inattention, hyperactivity and impulsivity, medication status and whether or not students lived at home or on-campus. Self-reported daytime sleepiness predicted longitudinally school maladjustment, overall functional impairment and the number of D and F grades (i.e. poor and failing) students received in courses above and beyond both self- and parent-report of symptoms, but did not predict overall grade point average. Living at home served as a protective factor and was associated with less school maladjustment and overall impairment. Gender was the only significant predictor in the overall grade point average model, with female gender associated with higher overall grades. The implications of these findings for monitoring and treatment of sleep disturbances in college students with attention deficit hyperactivity disorder are discussed.

  2. Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Edoardo Alessandro Pulixi

    Full Text Available BACKGROUND: A high prevalence of obstructive sleep apnea syndrome (OSAS has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD, but few studies have evaluated OSAS in non-morbidly obese NAFLD patients. AIMS: To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage. METHODS: We considered 159 consecutive patients with histological NAFLD and body mass index (BMI 1; 9/13, 69% vs. 39/146, 27%; p = 0.003. At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7-51, p = 0.005 and OR 14.0, 95% c.i. 3.5-70, p = 0.0002, respectively. CONCLUSIONS: A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

  3. When the going gets tough: behavioural type-dependent space use in the sleepy lizard changes as the season dries.

    Science.gov (United States)

    Spiegel, Orr; Leu, Stephan T; Sih, Andrew; Godfrey, Stephanie S; Bull, C Michael

    2015-11-22

    Understanding space use remains a major challenge for animal ecology, with implications for species interactions, disease spread, and conservation. Behavioural type (BT) may shape the space use of individuals within animal populations. Bolder or more aggressive individuals tend to be more exploratory and disperse further. Yet, to date we have limited knowledge on how space use other than dispersal depends on BT. To address this question we studied BT-dependent space-use patterns of sleepy lizards (Tiliqua rugosa) in southern Australia. We combined high-resolution global positioning system (GPS) tracking of 72 free-ranging lizards with repeated behavioural assays, and with a survey of the spatial distributions of their food and refuge resources. Bayesian generalized linear mixed models (GLMM) showed that lizards responded to the spatial distribution of resources at the neighbourhood scale and to the intensity of space use by other conspecifics (showing apparent conspecific avoidance). BT (especially aggressiveness) affected space use by lizards and their response to ecological and social factors, in a seasonally dependent manner. Many of these effects and interactions were stronger later in the season when food became scarce and environmental conditions got tougher. For example, refuge and food availability became more important later in the season and unaggressive lizards were more responsive to these predictors. These findings highlight a commonly overlooked source of heterogeneity in animal space use and improve our mechanistic understanding of processes leading to behaviourally driven disease dynamics and social structure.

  4. THE EFFECTS OF CRUDE RECOMBINANT VIRAL PROTEIN VACCINES AGAINST GROUPER SLEEPY DISEASE IRIDOVIRUS (GSDIV ON HUMPBACK GROUPER (Cromileptes altivelis

    Directory of Open Access Journals (Sweden)

    Ketut Mahardika

    2015-12-01

    Full Text Available Infection of Megalocytivirus cause serious mass mortality in marine fish in South East Asian countries. The aim of this study was to produce recombinant of GSDIV capsid protein and its protection to humpback grouper Cromileptes altivelis against grouper sleepy disease iridovirus (GSDIV. A major capsid protein (MCP was selected for use as a crude subunit vaccines. This gene target (MCP was inserted to the protein expression system vector of pET SUMO and cloned in cells bacteria Escherichia coli strain BL-21. The MCP was succeded to be induced using 1 mM of IPTG. Results of protein analysis using MALDI TOF-TOF indicated that the MCP has measurement of 49.566 kDa with PI index of 6.00, and contained 453 amino acids. BLAST homology analysis exhibited that the amino acid sequence of the MCP showed high similarity with MCP of Red Sea Bream Iridovirus (RSIV. E. coli expressing MCP protein was inactivated using 0.03% formalin overnight and washed using PBS. The inactivated E. coli as a crude subunit vaccine was then injected intramuscularly to humpback grouper juveniles. Subsequently, the juveniles were challenged tested with GSDIV. The juveniles vaccinated with the MCP recombinant bacteria showed significantly higher survival rates than control those vaccinated with PBS. Thus, the MCP fusion protein is considered as a potential vaccine against GSDIV infections in grouper.

  5. Microcurrent Stimulation at Shenmen Acupoint Facilitates EEG Associated with Sleepiness and Positive Mood: A Randomized Controlled Electrophysiological Study

    Directory of Open Access Journals (Sweden)

    Mei-chun Cheung

    2015-01-01

    Full Text Available To examine the electrophysiological effects of microcurrent stimulation at the Shenmen acupoint, 40 healthy normal subjects were randomly assigned to a placebo group (sham stimulation and an experimental group (bilateral electrocutaneous stimulation at the Shenmen. The following two electroencephalographic indicators were used to measure brain activity. (1 Arousal level was measured with reference to log-transformed absolute alpha power and power source and analyzed using low-resolution electromagnetic tomography and (2 frontal alpha asymmetry was used as an indicator of mood. After real stimulation for 10 minutes, absolute alpha power was globally reduced in the experimental group, particularly in the anterior and centrotemporal regions of the brain. This indicates a decline in the brain activity associated with arousal. Moreover, the reduction was more prominent in the left frontal region, as compared to the right frontal region, resulting in significant increase from negative to positive frontal alpha asymmetry scores and reflecting an increase in the brain activity associated with enhanced mood. However, the placebo group exhibited no significant changes in two indicators after sham stimulation. This study provides initial electrophysiological evidence of changes in brain activity associated with reduced arousal (and thus greater sleepiness and enhanced mood after microcurrent stimulation at the Shenmen acupoint.

  6. 药物诱导自身免疫性肝炎的研究进展%Progress in research of drug-induced autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    张彦亮; 史会连; 陶臻

    2011-01-01

    药物诱导自身免疫性肝炎(drug induced autoimmune hepatitis,DIAIH) 近年来国内外已有不少相关个案报道,其兼有药物性肝损(drug induced liver injury,DILI) 以及自身免疫性肝炎(autoimmune hepatitis,IH) 两者之特征,深入了解DIAIH 的流行病学现状、病因机制、临床表现和病理特点,将有助于我们加深对其的认知,并为DIAIH 的防治提供依据.%Drug-induced autoimmune hepatitis (DIAIH) has been reported to be caused by many drugs, which possesses the characteristics of both drug induced liver injury (DILI) and autoimmune hepatitis (AIH). A better understanding of the epidemiology, pathogenesis, pathology and clinical symptoms of DIAIH can help us better diagnose and treat this disease.

  7. 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.

    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 ca

  8. 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.

    2014-01-01

    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 ide

  9. 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.

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

    Science.gov (United States)

    Yoshizawa, Kunio; Moroi, Akinori; Kawashiri, Shuichi; Ueki, Koichiro

    2016-01-01

    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. PMID:27144039

  11. A Common Genetic Variant Risk Score is Associated with Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

    Science.gov (United States)

    Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Raymond; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

    2017-02-17

    Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, cross-over trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate corrected QT (QTc) vs. drug concentration. Results -The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide (r = 0.55 [95% CI, 0.09-0.81], P = 0.02), 23% in response to quinidine (r = 0.48 [95% CI, -0.03 to 0.79], P = 0.06) and 27% in response to ranolazine (r = 0.52 [95% CI, 0.05 to 0.80], P = 0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared to 771 controls (r(2) = 12%, P = 1x10(-7)). Conclusions -We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve

  12. 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 BACKGROUND: 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. OBJECTIVE: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network. METHODS: 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. RESULTS: 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. LIMITATIONS: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. CONCLUSION: A strategy to identify potentially drug-induced AMI from electronic healthcare

  13. 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

  14. 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.

  15. Effect of subclinical, clinical and supraclinical doses of calcium channel blockers on models of drug-induced hepatotoxicity in rats.

    Science.gov (United States)

    Okwa, Iniviefien B; Akindele, Abidemi J; Agbaje, Esther O; Oshinuga, Oladoyin T; Anunobi, Chidozie C; Adeyemi, Olufunmilayo O

    2013-01-01

    Drug-related hepatotoxicity is the leading cause of acute liver failure, and hepatic problems are responsible for a significant number of liver transplantations and deaths worldwide. Calcium has been associated with various metabolic processes that lead to cell death and apoptosis, and increased cytosolic Ca(2+) has been implicated in hepatotoxicity. This study was designed to investigate the effects of calcium channel blockers (CCBs) on isoniazid-rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment groups comprised control, hepatotoxicant, hepatotoxicant along with each of silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and supraclinical doses. A day to the end of treatment for each model, rats were subjected to the hexobarbitone-induced hypnosis test. On the last days of treatment, blood samples were collected and serum was analyzed for relevant biochemical parameters. Animals were sacrificed after blood collection and livers were harvested, and samples obtained for in vivo antioxidant indices assay and histopathology. The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA). The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The results obtained in this study suggest that the CCBs possess hepatoprotective activity in drug-induced hepatotoxicity and may be beneficial at the subclinical and clinical doses.

  16. TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival overgrowth.

    Science.gov (United States)

    Wright, H J; Chapple, I L; Matthews, J B

    2001-05-01

    Drug therapy and hereditary factors are two of the main causes of gingival overgrowth (GO). Both of these forms of GO are associated with increased extracellular matrix production by fibroblasts. Transforming growth factor beta (TGF-beta) is an important mediator of wound healing and tissue regeneration, which stimulates fibroblasts to produce extracellular matrix materials. The aim of this immunohistochemical study was to determine whether there is any altered expression of TGF-beta isoforms or its receptors in tissue from patients with drug-induced GO (DIGO; n=10) and hereditary gingival fibromatosis (n=10) when compared to non-overgrowth tissue (n=10). Compared to control tissues, significantly more fibroblasts expressed TGF-beta1 in both DIGO and hereditary gingival fibromatosis tissues (Pfibroblast densities between groups, there was a proportional increase in TGF-beta3 as well as TGF-beta1 expressing cells within both overgrowth populations (Preceptor-positive cells in the total cell population analysed in overgrowth tissues (Pisoform and receptor expression by fibroblasts in gingival overgrowth that may contribute to disease pathogenesis.

  17. Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial.

    Science.gov (United States)

    Johannesen, L; Vicente, J; Mason, J W; Erato, C; Sanabria, C; Waite-Labott, K; Hong, M; Lin, J; Guo, P; Mutlib, A; Wang, J; Crumb, W J; Blinova, K; Chan, D; Stohlman, J; Florian, J; Ugander, M; Stockbridge, N; Strauss, D G

    2016-02-01

    Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeak c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeak c may add value beyond only assessing QTc.

  18. Reprogramming of sheep fibroblasts into pluripotency under a drug-inducible expression of mouse-derived defined factors.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Animal embryonic stem cells (ESCs provide powerful tool for studies of early embryonic development, gene targeting, cloning, and regenerative medicine. However, the majority of attempts to establish ESC lines from large animals, especially ungulate mammals have failed. Recently, another type of pluripotent stem cells, known as induced pluripotent stem cells (iPSCs, have been successfully generated from mouse, human, monkey, rat and pig. In this study we show sheep fibroblasts can be reprogrammed to pluripotency by defined factors using a drug-inducible system. Sheep iPSCs derived in this fashion have a normal karyotype, exhibit morphological features similar to those of human ESCs and express AP, Oct4, Sox2, Nanog and the cell surface marker SSEA-4. Pluripotency of these cells was further confirmed by embryoid body (EB and teratoma formation assays which generated derivatives of all three germ layers. Our results also show that the substitution of knockout serum replacement (KSR with fetal bovine serum in culture improves the reprogramming efficiency of sheep iPSCs. Generation of sheep iPSCs places sheep on the front lines of large animal preclinical trials and experiments involving modification of animal genomes.

  19. 药物诱发的免疫性溶血性贫血%Drug-induced immune hemolytic anemia

    Institute of Scientific and Technical Information of China (English)

    刘代红

    2012-01-01

    药物诱发的免疫性溶血性贫血( DIIHA)少见.临床表现为中重度溶血性贫血常见机制是产生药物依赖性抗体,常见药物为抗生素(如头孢替坦、头孢曲松钠和哌拉西林).少见机制是产生非药物依赖的自身抗体,致特发性温抗体型自身免疫性溶血性贫血,最常见药物是氟达拉滨.治疗首要是停药,并积极处理合并症.%Drug-induced immune hemolytic anemia (DHHA) is seldom seen,whose clinical manifestation is mild-to-severe hemolytic anemia. The common mechanism is the presence of drug-dependent antibodies,and the common drugs are antibiotics, such as cefotetan,ceftriaxone and piperacillin. On other hand,the uncommon mechanism is the presence of non-drug-dependent antibodies that can lead to idiopathic autoimmune hemolytic anemia. In such case,the most common drug is flu-darabine. Importantly,drug use should be stopped and the complications be actively treated.

  20. Sustained attention to response task (SART) shows impaired vigilance in a spectrum of disorders of excessive daytime sleepiness.

    Science.gov (United States)

    Van Schie, Mojca K M; Thijs, Roland D; Fronczek, Rolf; Middelkoop, Huub A M; Lammers, Gert Jan; Van Dijk, J Gert

    2012-08-01

    The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with (n=42) and without cataplexy (n=5), idiopathic hypersomnia without long sleep time (n=37), and obstructive sleep apnoea syndrome (n=12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post-error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary.

  1. QUANTITATIVE HISTOPATHOLOGICAL ANALYSIS OF ENLARGED CELLS DERIVED FROM HUMPBACK GROUPER, Cromileptes altivelis INFECTED WITH GROUPER SLEEPY DISEASE IRIDOVIRUS (GSDIV

    Directory of Open Access Journals (Sweden)

    Indah Mastuti

    2010-12-01

    Full Text Available Pathognomonic sign of grouper sleepy disease iridovirus (GSDIV was proposed to be the formation of enlarged cells and necrotic cells, in which under electron microscope, it is revealed to be the inclusion body bearing cells (IBCs and necrotic cells containing GSDIV viral particles. Spleen and kidney tissues are the major sites for formation of enlarged cells. This paper described the result of histopatological analysis of enlarged cells found in the spleen and kidney of moribund fish after GSDIV challenge. A pathogenicity test was conducted on fish stocked in two tanks for infected groups and the other two tanks for uninfected control groups (15 fish per tank. The infected groups were injected intramuscularly with 0.1 ml of the viral inoculum. The uninfected groups were injected with the same amount of EMEM-2. The GSDIV-infected humpback grouper began to die after 6 days post infection and all died after 7 dpi, excluding one fish which had survived until the end of experimental infection periods (93% to 100% mortality. All of the diseased fish showed massive formation of enlarged cells in their spleen, head kidney and trunk kidney. The largest number of enlarged cells was observed on head kidneys and subsequently followed by spleens, trunk kidney (2.0-200.3/field of view. This result suggested that the number of enlarged cells in the affected organs was not the direct factor that led to the mortality of fish.

  2. Drug-induced diarrhea

    Science.gov (United States)

    ... cancer Drugs used to treat heartburn and stomach ulcers, such as omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (AcipHex), pantoprazole (Protonix), cimetidine (Tagamet), ranitidine ( ...

  3. Drug-induced tremor

    Science.gov (United States)

    ... medicine without first talking to your provider. Possible Complications Severe tremor can interfere with daily activities, especially fine motor skills such as writing, and other activities such ...

  4. Amelioration of anti-tuberculosis drug induced oxidative stress in kidneys by Spirulina fusiformis in a rat model.

    Science.gov (United States)

    Martin, Sherry Joseph; Sabina, Evan Prince

    2016-08-01

    Nephrotoxicity is a rare complication caused by anti-tuberculosis therapy-induced oxidative stress. The Cyanobacterium Spirulina fusiformis Voronikhin belonging to Oscillatoriaceae family is used traditionally as a source of antioxidants against oxidative stress. We aimed to investigate the efficacy of S. fusiformis in modifying isoniazid (INH) and rifampicin (RIF)-induced changes in Wistar rat kidneys. Animals were divided into six groups: normal control rats; toxic control (INH & RIF-50 mg/kg b.w./d each; p.o.); INH & RIF + S. fusiformis (400 mg/kg b.w./d); INH & RIF + S. fusiformis (800 mg/kg b.w./d); S. fusiformis (800 mg/kg b.w./d) alone-treated rats; INH & RIF + silymarin (25 mg/kg b.w./d). Study duration was 28 d after which blood and kidneys were analyzed. We also studied the binding and interactions of the transcription factors Liver X Receptor (LXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of S. fusiformis by in silico methods. INH & RIF treatment caused significant (p< 0.05) decrease in antioxidant levels and significant (p< 0.05) increase in the levels of creatinine, urea, and uric acid showing impaired kidney function. Spirulina fusiformis ameliorated these effects in a dose dependent manner. Histological examination of kidneys supported these findings. Results of the in silico analyses showed that selected active components of S. fusiformis interact with LXR and FXR and could be a possible mechanism of action. S. fusiformis rendered protection against anti-tuberculosis drugs-induced oxidative stress in kidney tissues of rats.

  5. A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: application to acetaminophen

    Science.gov (United States)

    Michaut, Anaïs; Le Guillou, Dounia; Moreau, Caroline; Bucher, Simon; McGill, Mitchell R.; Martinais, Sophie; Gicquel, Thomas; Morel, Isabelle; Robin, Marie-Anne; Jaeschke, Hartmut; Fromenty, Bernard

    2016-01-01

    Obesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations of insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5 mM) or high (20 mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicity. PMID:26739624

  6. An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US

    Science.gov (United States)

    Zeng, Lily; Alongkronrusmee, Doungkamol; van Rijn, Richard M

    2017-01-01

    Neuropathic pain (NeuP) is a syndrome that results from damaged nerves and/or aberrant regeneration. Common etiologies of neuropathy include chronic illnesses and medication use. Chronic disorders, such as diabetes and alcoholism, can cause neuronal injury and consequently NeuP. Certain medications with antineoplastic effects also carry an exquisitely high risk for neuropathy. These culprits are a few of many that are fueling the NeuP epidemic, which currently affects 7%–10% of the population. It has been estimated that approximately 10% and 7% of US adults carry a diagnosis of diabetes and alcohol disorder, respectively. Despite its pervasiveness, many physicians are unfamiliar with adequate treatment of NeuP, partly due to the few reviews that are available that have integrated basic science and clinical practice. In light of the recent Centers for Disease Control and Prevention guidelines that advise against the routine use of μ-opioid receptor-selective opioids for chronic pain management, such a review is timely. Here, we provide a succinct overview of the etiology and treatment options of diabetic and alcohol- and drug-induced neuropathy, three different and prevalent neuropathies fusing the combined clinical and preclinical pharmacological expertise in NeuP of the authors. We discuss the anatomy of pain and pain transmission, with special attention to key ion channels, receptors, and neurotransmitters. An understanding of pain neurophysiology will lead to a better understanding of the rationale for the effectiveness of current treatment options, and may lead to better diagnostic tools to help distinguish types of neuropathy. We close with a discussion of ongoing research efforts to develop additional treatments for NeuP. PMID:28176937

  7. Drug-Induced Sleep Endoscopy (DISE) with Target Controlled Infusion (TCI) and Bispectral Analysis in Obstructive Sleep Apnea.

    Science.gov (United States)

    Traxdorf, Maximilian; Tschaikowsky, Klaus; Scherl, Claudia; Bauer, Judith; Iro, Heinrich; Angerer, Florian

    2016-12-06

    The aim of this study was to establish a standardized protocol for drug-induced sleep endoscopy (DISE) to differentiate obstruction patterns in obstructive sleep apnea (OSA). Target-controlled infusion (TCI) of the sedative propofol was combined with real-time monitoring of the depth of sedation using bispectral analysis. In an observational study 57 patients (mean age 44.8 years, ± SD 10.5; mean apnea hypopnea Index (AHI) 30.8/hr, ± SD 21.6, mean BMI 28.2 kg/m(2), ± SD 5.3) underwent cardiorespiratory polysomnography followed by DISE with TCI and bispectral analysis. Sleep was induced solely by the intravenous infusion of propofol with a TCI-pump, with an initial target plasma level of 2.0 µg/ml. Under continuous monitoring of the patient's respiration, state of consciousness and value of the bispectral analysis, the target plasma propofol level was raised in steps of 0.2 µg/ml/2 min until the desired depth of sedation was reached. The mean value of the bispectral analysis at the target depth of sedation was determined and the obstruction patterns during DISE-TCI-bispectral analysis then classified according to the VOTE-system. Subsequently the results were analyzed according to polysomnographic and anthropometric data. The occurrence of multilevel obstruction sites across all degrees of severity of OSA clarifies the need for sleep endoscopy prior to upper airway surgery. The advantage of this technique is the reproducibility of the protocol even for heterogeneous groups of patients. In addition, the gradual controlled and standardized increase of the plasma level of propofol with real-time control of the bispectral index leads to a precisely controllable depth of sedation. The DISE-TCI-bispectral analysis procedure is a step towards a required reproducible protocol of sleep endoscopy - capable of standardization. However it is not yet known whether these observed obstruction patterns also correspond to findings in natural sleep.

  8. Development of a prediction system for anti-tuberculosis drug-induced liver injury in Japanese patients

    Science.gov (United States)

    Mushiroda, Taisei; Yanai, Hideki; Yoshiyama, Takashi; Sasaki, Yuka; Okumura, Masao; Ogata, Hideo; Tokunaga, Katsushi

    2016-01-01

    Drug-induced liver injury (DILI) is a common adverse drug reaction in patients receiving antituberculosis (anti-TB) treatment. Among the anti-TB agents, isoniazid (INH) is the primary drug that causes hepatotoxicity in TB patients with DILI. Previous reports in several populations have consistently demonstrated an association between polymorphisms in the N-acetyltransferase 2 (NAT2) gene, which is responsible for INH hepatic metabolism, and a risk of DILI in TB patients. In this study, the genetic and baseline clinical data from 366 Japanese patients with TB (73 patients with DILI and 293 without DILI) were used to develop a system to predict DILI risk due to anti-TB agents. The distribution of the NAT2 acetylator status among the TB patients with DILI was 31 (42.5%), 29 (39.7%), and 13 (17.8%) for rapid, intermediate, and slow acetylators, respectively. A significant association was observed between NAT2 slow acetylators and DILI risk (odds ratio 4.32, 95% confidence interval 1.93–9.66, P value=5.56×10−4). A logistic regression model based on age and NAT2 genotype revealed that the area under the curve for the receiver-operating characteristic curve was 0.717. The findings demonstrated that slow NAT2 acetylator status is a significant predictor of the risk of DILI by anti-TB agents, and a personalized anti-TB treatment approach may aid in making treatment decisions and reducing the incidence of DILI. PMID:27340556

  9. Prediction of Drug-Induced Liver Injury in HepG2 Cells Cultured with Human Liver Microsomes.

    Science.gov (United States)

    Choi, Jong Min; Oh, Soo Jin; Lee, Ji-Yoon; Jeon, Jang Su; Ryu, Chang Seon; Kim, Young-Mi; Lee, Kiho; Kim, Sang Kyum

    2015-05-18

    Drug-induced liver injury (DILI) via metabolic activation by drug-metabolizing enzymes, especially cytochrome P450 (CYP), is a major cause of drug failure and drug withdrawal. In this study, an in vitro model using HepG2 cells in combination with human liver microsomes was developed for the prediction of DILI. The cytotoxicity of cyclophosphamide, a model drug for bioactivation, was augmented in HepG2 cells cultured with microsomes in a manner dependent on exposure time, microsomal protein concentration, and NADPH. Experiments using pan- or isoform-selective CYP inhibitors showed that CYP2B6 and CYP3A4 are responsible for the bioactivation of cyclophosphamide. In a metabolite identification study employing LC-ESI-QTrap and LC-ESI-QTOF, cyclophosphamide metabolites including phosphoramide mustard, a toxic metabolite, were detected in HepG2 cells cultured with microsomes, but not without microsomes. The cytotoxic effects of acetaminophen and diclofenac were also potentiated by microsomes. The potentiation of acetaminophen cytotoxicity was dependent on CYP-dependent metabolism, and the augmentation of diclofenac cytotoxicity was not mediated by either CYP- or UDP-glucuronosyltransferase-dependent metabolism. The cytotoxic effects of leflunomide, nefazodone, and bakuchiol were attenuated by microsomes. The detoxication of leflunomide by microsomes was attributed to mainly CYP3A4-dependent metabolism. The protective effect of microsomes against nefazodone cytotoxicity was dependent on both CYP-mediated metabolism and nonspecific protein binding. Nonspecific protein binding but not CYP-dependent metabolism played a critical role in the attenuation of bakuchiol cytotoxicity. The present study suggests that HepG2 cells cultured with human liver microsomes can be a reliable model in which to predict DILI via bioactivation by drug metabolizing enzymes.

  10. Hepatoprotective activity of aqueous alcoholic (70% extract of Rhodomyrtus tomentosa (Aiton Hassk against antitubercular drugs induced hepatic damage

    Directory of Open Access Journals (Sweden)

    Kannoth Mukundan Geetha

    2012-01-01

    Full Text Available Background: Rhodomyrtus tomentosa of family Myrtaceae has been used traditionally in Chinese medicine for the treatment of liver disorders. However, there is no scientific evidence on the hepatoprotective potential of the plant. Aim: The present study was aimed at evaluating the hepatoprotective and antioxidant potential of the aqueous alcoholic (70% extract of Rhodomyrtus tomentosa leaves (RTLE based on its traditional claim in liver diseases. Materials and Methods: Hepatotoxicity was induced in albino rats by administering a combination of three antitubercular drugs, Isoniazid (7.5 mg/kg, Pyrazinamide (35 mg/kg and Rifampicin (10 mg/kg orally for 45 days. Alkaline phosphatase (ALP, Aspartate amino transferase (AST, Alanine aminotransferase (ALT, total protein and total bilirubin (TB levels were estimated in serum samples using diagnostic kits. Antioxidant parameters were estimated in liver homogenates using standard methods. Statistical Analysis: The experimental mean values were compared statistically with that of toxicant group by using One-way ANOVA followed by Newman-Keul′s multiple tests. Results: Hepatoprotective activity of the extract was evident from the significant decrease in the elevated levels of ALT, AST, ALP and total bilirubin and an increase in the levels of total protein in comparison to toxicant control. Increased activity of antioxidant enzymes supports the in vivo antioxidant activity of the extract. Histopathological changes of the liver in the treated and control group of rats were in agreement with the hepatoprotective finding. Conclusion: RTLE exhibited hepatoprotective activity against antitubercular drug induced hepatotoxicity through a free radical scavenging effect and reduces oxidative damage caused by antitubercular drugs.

  11. Upper airway collapse during drug induced sleep endoscopy: head rotation in supine position compared with lateral head and trunk position.

    Science.gov (United States)

    Safiruddin, Faiza; Koutsourelakis, Ioannis; de Vries, Nico

    2015-02-01

    Drug induced sedated sleep endoscopy (DISE) is often employed to determine the site, severity and pattern of obstruction in patients with sleep apnea. DISE is usually performed in supine position. We recently showed that the obstruction pattern is different when DISE is performed in lateral position. In this study, we compared the outcomes of DISE performed in supine position with head rotated, with the outcomes of DISE performed with head and trunk in lateral position. The Prospective study design was used in the present study. Sixty patients with OSA (44 male; mean apnea hypopnea index (AHI) 20.8 ± 17.5 events/h) underwent DISE under propofol sedation. Patients were placed in lateral position, and the upper airway collapse was evaluated. The patients were then placed in supine position with the head rotated to the right side. DISE outcomes were scored using the VOTE classification system. In lateral position, nine patients (15.0%) had a complete antero-posterior (A-P) collapse at the level of the velum, nine had a partial A-P collapse. During head rotation and trunk in supine position, at the level of the velum, four patients (6.7%) had a complete A-P collapse, while two patients (3.3%) had a partial A-P collapse. For all other sites, the patterns of collapse were not significantly different between head rotation and lateral position. During DISE, rotation of the head in supine position, and lateral head and trunk position present similar sites, severity and patterns of upper airway collapse, with the exception of collapse at the level of the velum. Here the severity of A-P collapse is less severe during head rotation than in lateral head and trunk position.

  12. The anti-cancer drug-induced pica in rats is related to their clinical emetogenic potential.

    Science.gov (United States)

    Yamamoto, Kouichi; Nakai, Miho; Nohara, Kyoko; Yamatodani, Atsushi

    2007-01-05

    Cancer chemotherapy is frequently accompanied by severe emesis. The anti-cancer drugs are classified according to their clinical emetogenic potential. We have already found that kaolin ingestion behavior "pica" is analogous to emesis in rats. The aim of this study was to examine the effects of the clinical emetogenic potential of anti-cancer drugs on the induction of the pica in rats. Rats were housed in individual cages with free access to food and kaolin pellets and the daily food and kaolin intakes were measured for 3 days after the intraperitoneal administration of anti-cancer drugs (cisplatin, cyclophosphamide, actinomycin D, 5-fluorouracil and vincristine). The drugs with high potential for inducing emesis, such as cisplatin and cyclophosphamide, induced pica in all animals on the day of administration and the behavior lasted during the observation period. The drugs with moderate emetogenic potential, i.e. actinomycin D and 5-fluorouracil, also induced pica on the first and second day after the drug administration but the kaolin intake was less than that of the drugs with high potential. Vincristine, a drug with low emetogenic potential, slightly increased the kaolin intake in rats on the only first day of the administration. Cyclophosphamide, actinomycin D and vincristine induced anorexia and decreased their body weight during the observation period. These results suggested that the both amounts of kaolin intake and duration of behavior in the anti-cancer drug-induced pica are related to the clinical emetogenic potential of the drugs and the incidence of the anorexia is not related to their emetogenic potential.

  13. 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...... cytometric DNA analysis. Melphalan produced a dose-related S phase accumulation in the two sensitive tumors, whereas no changes in the cell cycle distribution were found in the resistant tumor. The size of S phase accumulation correlated to the chemosensitivity in vivo. For low concentrations of melphalan...

  14. Identification and Treatment of Psychotropic Drug-induced Alopecia%精神药物致脱发的识别与处理

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 于相芬

    2014-01-01

    多种精神药物可引起脱发,本文对脱发的概念、精神药物所致脱发的诊断、鉴别诊断、发病机制及处理等作一综述,以提高临床对精神药物所致脱发的认识。%A variety of psychotropic drugs can cause alopecia . In order to make a better understanding of psy-chotropic drug-induced alopecia , this article made a review on the definition of alopecia , diagnosis , differential diag-nosis , pathomechanism and the treatment of psychotropic drug-induced alopecia .

  15. Experience with the use of modafinil in the treatment of narcolepsy in a outpatient facility specialized in diurnal excessive sleepiness in São Paulo

    Directory of Open Access Journals (Sweden)

    Nilce Sanny Costa da Silva Behrens

    2014-03-01

    Full Text Available Narcolepsy is a chronic neurological disease characterized by diurnal excessive sleepiness and catapleaxy. It affects 1 in every 2000 to 4000 individuals with personal, social and familiar significant repercussions. The treatment of narcolepsy is mainly based on the use of stimulants for the control of the diurnal excessive sleepiness, in conjunction with behavioral measures and sleep hygiene. Among the stimulants, modafinil has presently been the drug of choice for the treatment of the diurnal excessive sleepiness in patients with narcolepsy. In the worldwide experience, its use is better tolerated and the majority of its side effects is considered light or moderate. However, the clinical use in Brazil was initiated at the end of 2008, with little experience on the narcolepsy population of this country. In this context, the objective of this study was the evaluation of the use of modafinil, verifying the indication of use, causes for discontinuation, daily dosage, efficiency of the treatment in a patient sample of narcoleptics consulted in a specialized center in Brazil. In this study, modafinil was effective for the control of the symptoms related do narcolepsy in 66% of the studied patients. The side effects such as headache, parestesias and diarrhea were the main reasons for the discontinuation of treatment with modafinil. It is important to clinically follow up the patients for a long period to evaluate symptomatology, control of use, tolerability and re-evaluation of the more effective therapeutic dosage able to control narcolepsy. Due to its high cost and clinical benefits, this drug should be on the government׳s list of free drugs for the treatment of these patients.

  16. Clinical Analysis of 1 056 Cases of Drug-induced Hematuria in Children%儿童药物性血尿1056例临床分析

    Institute of Scientific and Technical Information of China (English)

    王玉刚; 张亚明

    2011-01-01

    目的:探讨儿童药物性血尿的原因和机制,提出预防措施,促进临床合理用药.方法:对2005-2010年国内公开发表的医药期刊报道的1 056例儿童(≤16岁)药物性血尿进行统计、分析.结果:本研究中药物性血尿共涉及5类药物41个品种,以抗微生物药、解热镇痛抗炎药和抗感冒药为主,且与年龄、给药剂量、给药途径等有关.结论:充分认识药物性血尿产生的原因,安全、合理地使用药品,积极采取预防措施,对避免或减少儿童药物性血尿的发生有重要的临床意义.%OBJECTIVE: To investigate the characteristics and regularity of drug-induced hematuria in children, and to put forwards prevention measures in order to promote rational use of drugs in the clinic. METHODS: We summarized and analyzed 1056 cases of drug-induced hematuria in children (≤16 years old) published on public medical journals from 2005 to 2010. RESULTS: 5 categories and 41 kinds of drugs were involved, which included anti-microbial drugs, antipyretics-analgesic and anti-inflammatory drugs, anti-cold drugs. Besides, some cases happened due to patients' age, drug dosage, route of administration, etc. CONCLUSIONS: We come to recognize the causes of drug-induced hematuria, use drugs safely and properly, take preventive measures actively to avoid or reduce drug-induced hematuria in children.

  17. Literature Analysis of 66 Cases of Drug-induced Hyperkalemia%66例药源性高钾血症文献分析

    Institute of Scientific and Technical Information of China (English)

    任晓蕾; 詹轶秋; 张春燕; 张海英; 冯婉玉

    2015-01-01

    目的:探讨药源性高钾血症的特点及相关因素,为临床合理用药提供依据。方法:检索1979-2014年国内医药期刊公开报道的药源性高钾血症的个案和群案文献46篇,共计病例66例,并进行统计分析。结果:66例药源性高钾血症病例中主要涉及心血管药物和免疫抑制剂。大部分停药及对症治疗后好转,其中2例患者死亡。结论:药物诱发高钾血症具有潜在的危险性,需提高警惕,重视防治。%OBJECTIVE:To investigate the characteristics and related factors of drug-induced hyperkalemia,present preven-tive measures and provide reference for the rational drug use. METHODS:46 literatures of individual cases and group cases of drug-induced hyperkalemia publicly reported in domestic medical journals from 1979 to 2014 were collected and analyzed statistical-ly,including 66 cases. RESULTS:66 cases with drug-induced hyperkalemia were mainly involved in cardiovascular drugs and im-munosuppressants. Most of them were improved after drug withdrawal and symptomatic treatment,and 2 cases died. CONCLU-SIONS:Drug-induced hyperkalemia are potentially dangerous. It is necessary to be vigilant,prevent and control timely and reduce the incidence of severe adverse reactions.

  18. The viability of an ecologically valid chronic sleep restriction and circadian timing protocol: An examination of sample attrition, compliance, and effectiveness at impacting sleepiness and mood

    Science.gov (United States)

    Drummond, Sean P. A.; McElroy, Todd

    2017-01-01

    Chronic sleep restriction (SR) increases sleepiness, negatively impacts mood, and impairs a variety of cognitive performance measures. The vast majority of work establishing these effects are tightly controlled in-lab experimental studies. Examining commonly-experienced levels of SR in naturalistic settings is more difficult and generally involves observational methods, rather than active manipulations of sleep. The same is true for analyzing behavioral and cognitive outcomes at circadian unfavorable times. The current study tested the ability of an at-home protocol to manipulate sleep schedules (i.e., impose SR), as well as create a mismatch between a subject’s circadian preference and time of testing. Viability of the protocol was assessed via completion, compliance with the SR, and success at manipulating sleepiness and mood. An online survey was completed by 3630 individuals to assess initial eligibility, 256 agreed via email response to participate in the 3-week study, 221 showed for the initial in-person session, and 184 completed the protocol (175 with complete data). The protocol consisted of 1 week at-home SR (5-6 hours in bed/night), 1 week wash-out, and 1 week well-rested (WR: 8-9 hours in bed/night). Sleep was monitored with actigraphy, diary, and call-ins. Risk management strategies were implemented for subject safety. At the end of each experimental week, subjects reported sleepiness and mood ratings. Protocol completion was 83%, with lower depression scores, higher anxiety scores, and morning session assignment predicting completion. Compliance with the sleep schedule was also very good. Subjects spent approximately 2 hours less time in bed/night and obtained an average of 1.5 hours less nightly sleep during SR, relative to WR, with 82% of subjects obtaining at least 60 minutes less average nightly sleep. Sleepiness and mood were impacted as expected by SR. These findings show the viability of studying experimental chronic sleep restriction outside

  19. Research Advances in Drug-induced Autoimmune Disordersw%药物诱导性自身免疫性疾病的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟佩茹

    2011-01-01

    药物诱导性自身免疫性疾病是长期用药引发的一种不良反应,其作用机制因药物种类不同而不同.但最终会因机体丧失对自身抗原的免疫耐受而产生自身抗体.认识原发性和药物诱导性自身免疫反应,将有助于提高对这些疾病机制的理解.并且通过分析药物诱导性自身免疫性疾病的发病机制,为药物不良反应的预防以及临床治疗提供帮助.%Drug-induced autoimmune disease is an adverse effect caused by the long-term use of drug. The mechanisma of actions depend the properties of drugs. The auto-antibodies are produced due to the loss of immune tolerance to the auto-antigens. The understanding of primary and drug-induced autoimmune response helps to improve the study of the pathogenesis of drug-induced autoimmune disease. The analysis.f pathogenesis of drug-in-duced autoimmune disease helps to improve the prevention and treatment of adverse drug reactions.

  20. 181例药源性肺水肿文献分析%Literature Analysis of 181 Cases of Drug-induced Pulmonary Edemas

    Institute of Scientific and Technical Information of China (English)

    张艳丛

    2011-01-01

    OBJECTIVE To discuss the characteristics and general pattern of drug-induced pulmonary edemas. METHODS A total of 181 drug-induced pulmonary edema cases reported in internal medical journals published from January 1990 to April 2010 were collected by retrieving China Hospital Digital Library and analyzed statistically. RESULTS Leading the routes of administration inducing pulmonary edemas were oral administration, intramuscular injection, intravenous administration, and so on. The pulmonary edemas were predominantly caused by anti-psychotic drug and dehydration drugs. CONCLUSION Clinic should attach great importance to drugs-induced pulmonary edemas.%目的 探讨药物引起肺水肿的特点及一般规律.方法 检索,对1990年1月-2010年4月国内医药学术期刊报道的药物引起肺水肿181例进行统计、分析.结果 药物引起肺水肿的给药途径为口服给药、肌肉注射、静脉给药等;引起肺水肿的药物种类以抗精神病药、利尿脱水药较多.结论 临床应重视药物引起的肺水肿.

  1. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  2. Sleep habits, sleepiness and accidents among truck drivers Hábitos de sono, sonolência e acidentes em caminhoneiros

    Directory of Open Access Journals (Sweden)

    José Carlos Souza

    2005-12-01

    Full Text Available OBJECTIVE: To evaluate the quality of sleep, shift work, alcohol and psychostimulant drug use, and the prevalence of accidents among truck drivers. METHOD: Data were collected using a demographic questionnaire, the Epworth Sleepiness Scale (ESS and the Pittsburgh sleep quality index (PSQI. Statistical analysis was conducted using the Student t, chi-square, Pearson and Fisher tests. RESULTS: 43.2% of the drivers drove over 16 h a day, and 2.9% worked shifts. Mean number of sleep hours/day was 5.97±1.47; 23.8% slept 5; 23 subjects snored more than three times a week (11.1%. Mean ESS was 6.56±4.2; 21.7% had a score >10. In the preceding five years, 27 drivers (13.1% were involved in accidents, 5 of which resulted in injuries and 3 in deaths. CONCLUSION: Results showed a high prevalence of sleep disorders, use of alcohol and psychostimulant drugs, and accidents.OBETIVO: Avaliar a qualidade do sono, trabalho em turnos, consumo de álcool e psicoestimulantes, e a prevalência de acidentes, entre caminhoneiros. MÉTDO: Foram aplicados questionários demográficos, a Escala de Epworth e o Índice de Pittsburgh. A análise estatística foi feita com os testes t de Student, qui-quadrado, Pearson e Fisher. RESULTADOS: 43,2% dirigiam mais que 16 h/dia; 2,9% faziam trabalho por turnos. A média de horas de sono foi 5,97 +/- 1,47. 23,8% dormiam menos de 5 horas. 50,9% faziam uso de bebida alcoólica; usavam cafeína 95,6% e anfetaminas 11,1%. A média do PSQI foi 4,95 +/- 2,56; 35,4% tinham o PSQI maior que 5; 23 sujeitos ressonavam mais que 3 vezes por semana (11,1%. A ESE teve uma média de 6,56 +/- 4,2; 21.7% um escore superior a 10. Nos últimos cinco anos 27 motoristas (13,1% estiveram envolvidos em acidentes, 5 com feridos e 3 com mortos. CONCLUSÃO: Foi alta a prevalência de distúrbios do sono, uso de álcool e estimulantes, e de acidentes.

  3. Are Sleepy Students Learning?

    Science.gov (United States)

    Willingham, Daniel T.

    2013-01-01

    Cognitive science is an interdisciplinary field of researchers from psychology, neuroscience, linguistics, philosophy, computer science, and anthropology who seek to understand the mind. This paper considers findings from this field that are strong and clear enough to merit classroom application. Although many teachers and parents worry that high…

  4. Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial.

    Science.gov (United States)

    Tembe, D V; Dhavale, A; Desai, H; Mane, D N; Raut, S K; Dhingra, G; Sardesai, U; Saoji, S; Rohra, M; Shinde, V G; Padsalge, M; Paliwal, A; Abbasi, K; Devnani, P; Papinwar, S; Phadke, S; Mehta, H; Bhailume, V

    2011-01-01

    Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg.

  5. Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

    Directory of Open Access Journals (Sweden)

    D. V. Tembe

    2011-01-01

    Full Text Available Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD. Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg or modafinil (200 mg one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS by at least 2 grades (responder and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (<.0001. Responder rates with armodafinil (72.12% and modafinil (74.29% were comparable (=.76. Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg.

  6. Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apnea.

    Science.gov (United States)

    Roth, Thomas; Rippon, Gregory A; Arora, Sanjay

    2008-03-01

    Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some patients with obstructive sleep apnea (OSA). A pooled analysis of two 12-week, randomized, double-blind studies in nCPAP-adherent patients with ES associated with OSA evaluated the effect of armodafinil on wakefulness and cognition. Three hundred and ninety-one patients received armodafinil (150 or 250 mg) and 260 patients received placebo once daily for 12 weeks. Efficacy assessments included the Maintenance of Wakefulness Test (MWT), Cognitive Drug Research cognitive performance battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. Adverse events were monitored. Armodafinil increased mean MWT sleep latency from baseline to final visit by 2.0 min vs a decrease of 1.5 min with placebo (P armodafinil significantly improved quality of episodic secondary memory (P Armodafinil did not adversely affect desired nighttime sleep, and nCPAP use remained high (approximately 7 h/night). Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients' ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. Armodafinil also reduced patient-reported fatigue and was well tolerated.

  7. 日间嗜睡与急性缺血性卒中短期预后的关系%Correlation of Daytime Sleepiness and Acute Ischemic Stroke

    Institute of Scientific and Technical Information of China (English)

    谢子珍; 李常红; 孟晓梅; 于逢春

    2016-01-01

    Objective By analyzing the relationship between daytime sleepiness and neurological function prognosis in patients with acute stroke, to explore the relationship between daytime sleepiness and acute ischemic stroke. Methods Patients with acute ischemic stroke within 48 hours were consecutively enrolled from Beijing Haidian Hospital during June 2015 to September, 2015. And data were collected including demographics, chronic disease history, National Institutes of Health Stroke Scale (NIHSS) on admission and the 14th day, and Epworth Sleepiness Scale (ESS) on admission. ESS 1 month before admission, which is the premorbid ESS, were retrospectively evaluated. The correlation between premorbid ESS with demographics, chronic disease history, NIHSS on admission and the 14th day, delta NIHSS (the result of NIHSS on admission minus NIHSS of the 14th day) and ESS on admission were analyzed. According to premorbid ESS, patients were divided into sleepiness group and non-sleepiness group, compared NIHSS on admission and the 14th day, delta NIHSS and ESS on admission between two groups. Results One hundred and six patients were consecutively enrolled. The results showed that①Premorbid ESS had positive correlation with admission NIHSS, the 14th day NIHSS and admission ESS. Pearson correlation coefifcient were 0.199, 0.276 and 0.407, andP values were 0.041, 0.004 and Conclusion Premorbid daytime sleepiness patients will be more severely on admission and in 14th day, meanwhile their prognosis in the acute phase is worse. The degree of daytime sleepiness will aggravate when ischemic stroke happens.%目的通过分析急性缺血性卒中患者日间嗜睡及急性期神经功能转归情况,探索日间嗜睡与急性缺血性卒中短期预后之间的关系。  方法连续收集2015年6月-2015年9月北京市海淀医院神经内科收治的发病48 h内的住院急性缺血性卒中患者临床资料,包括:人口学特征、既往病史、入院时及发病14 d

  8. Effects of a selective educational system on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan

    Directory of Open Access Journals (Sweden)

    Chen TY

    2015-03-01

    Full Text Available Tien-Yu Chen,1,2 Yu-Ching Chou,3 Nian-Sheng Tzeng,1,2,4 Hsin-An Chang,1,2,4 Shin-Chang Kuo,1,2,5 Pei-Yin Pan,1,2 Yi-Wei Yeh,1,2,5 Chin-Bin Yeh,1,2 Wei-Chung Mao1,2,6 1Department of Psychiatry, Tri-Service General Hospital, 2School of Medicine, National Defense Medical Center, 3School of Public Health, National Defense Medical Center, 4Student Counseling Center, National Defense Medical Center, 5Graduate Institute of Medical Sciences, National Defense Medical Center, 6Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, Republic of China Objective: The aim of the study reported here was to clarify the effects of academic pressure on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan. Methods: This cross-sectional study enrolled 757 senior high school adolescents who were classified into four groups: Grade 1 (n=261, Grade 2 (n=228, Grade 3T (n=199; Grade 3 students who had another college entrance test to take, and Grade 3S (n=69; Grade 3 students who had succeeded in their college application. Fatigue, sleep quality, daytime sleepiness, and depression were assessed using the Chinese version of the Multidimensional Fatigue Symptom Inventory – Short Form, Pittsburgh Sleep Quality Index-Taiwan Form, the Chinese version of the Epworth Sleepiness Scale, and the Chinese version of the Beck Depression Inventory®-II (BDI-II, respectively. Results: Physical, emotional, and mental fatigue scores were all higher in higher-grade groups. The Grade 3T (test students had the worst fatigue severity, and the Grade 3S (success students had the least fatigue severity. More than half of the students (60.9% went to bed after 12 am, and they had on average 6.0 hours of sleep per night. More than 30% of the students in Grade 2 (37.3% and Grades 3T/S (30.2%/30.4% possibly had daily sleepiness problems. The students in Grade 3T had the worst BDI-II score (13.27±9.24, and the Grade 3S

  9. Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

    Directory of Open Access Journals (Sweden)

    Hasegawa Yoshinori

    2009-09-01

    Full Text Available Abstract Background To determine whether oral administration of geranylgeranylacetone (GGA, a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP 70, protects against drug-induced lung injury/fibrosis in vivo. Methods We used a bleomycin (BLM-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2 in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry. Results We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice. Conclusion GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.

  10. Excessive daytime sleepiness and adherence to antihypertensive medications among Blacks: analysis of the counseling African Americans to control hypertension (CAATCH trial

    Directory of Open Access Journals (Sweden)

    Williams NJ

    2014-03-01

    Full Text Available Natasha J Williams,1 Girardin Jean-Louis,1 Abhishek Pandey,2 Joseph Ravenell,1 Carla Boutin-Foster,3 Gbenga Ogedegbe1 1Center for Healthful Behavior Change, Division of Internal Medicine, NYU Medical Center, New York, 2Department of Family Medicine, SUNY Downstate Medical Center, Brooklyn, 3Center of Excellence in Disparities Research, Weill Cornell Medical College, New York, NY, USA Background: Excessive daytime sleepiness (EDS often occurs as a result of insufficient sleep, sleep apnea, illicit substance use, and other medical and psychiatric conditions. This study tested the hypothesis that blacks exhibiting EDS would have poorer self-reported adherence to hypertensive medication using cross-sectional data from the Counseling African-Americans to Control Hypertension (CAATCH trial. Methods: A total of 1,058 hypertensive blacks (average age 57±12 years participated in CAATCH, a randomized controlled trial evaluating the effectiveness of a multilevel intervention for participants who receive care from community health centers in New York City. Data analyzed in this study included baseline sociodemographics, medical history, EDS, and medication adherence. We used the Epworth Sleepiness Scale, with a cutoff score of ≥10, to define EDS. Medication adherence was measured using an abbreviated Morisky Medication Adherence scale, with a score >0 indicating nonadherence. Results: Of the sample, 71% were female, 72% received at least a high school education, 51% reported a history of smoking, and 33% had a history of alcohol consumption. Overall, 27% of the participants exhibited EDS, and 44% of those who exhibited EDS were classified as adherent to prescribed antihypertensive medications. Multivariable logistic regression analysis, adjusting for effects of age, body mass index, sex, education, and smoking and drinking history indicated that participants who exhibited EDS were more than twice as likely to be nonadherent (odds ratio 2.28, 95

  11. Drug-induced chimerism and prevention of graft-versus-host disease in lethally irradiated mice transplanted with rat bone marrow. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pierpaoli, W.; Maestroni, G.J.M.

    1978-12-01

    L-5-hydroxytryptophan, haloperidol, and phentolamine were administered subcutaneously to groups of mice. Some groups were inoculated i.p. or i.v. with bone marrow cells. The mice were given a dose of 900 rad of whole-body gamma radiation. Observations were made on survival rate, reconstitution with rat hematopoietic tissue, and capacity to reject or accept skin grafts. Results indicate that the combination of drug-induced tolerance and a newly established preconditioning regimen that eliminated postradiation damage and mortality results in reduction in incidence or delay in onset of GVHD, successful bone marrow grafting, and induction of persistent rat chimerism. (HLW)

  12. Clinical observation of 60 cases of drug induced liver disease%药物性肝病60例临床观察

    Institute of Scientific and Technical Information of China (English)

    马志敏

    2016-01-01

    目的:观察分析药物性肝病患者的疾病类型、预后情况以及影响因素。方法:收治药物性肝病患者60例,对其进行回顾性分析。结果:60例患者临床症状、体征表现与临床分型各有不同;HBsAg呈阴性影响相关性大,阳性相关性小;患者长期饮酒习惯相关性大;不同类型药物长期服用相关性大;采用有效治疗措施可对药物性肝病患者起到良好的治疗效果。结论:药物性肝病的发病因素与患者饮酒习惯、用药史、病症史等具有较大的相关性,在停药采取积极治疗后,可取得较好的治疗效果。%Objective:To observe and analyze the disease type,prognosis and influencing factors of drug induced liver disease. Methods:60 cases of drug induced liver disease were selected.We analyzed the data of them retrospectively.Results:The clinical manifestation,signs expression and clinical types of 60 patients were different;HBsAg showed negative correlation was big,and the positive correlation was small;long term drinking habits of patients with large correlation;long-term use of different types of drugs related to large;the effective treatment can had good therapeutic effect when used to treat patients with drug-induced liver disease. Conclusion:The factors of drug induced liver disease are related to drinking habits,history of drug use,history of disease and so on. Stopping the medicine to take the active treatment can obtain the good treatment effect.

  13. 心肺复苏发展史及2010指南简介%Statistic analysis of the 9355 patients with drug induced liver injury

    Institute of Scientific and Technical Information of China (English)

    程立顺; 李从圣

    2011-01-01

    Aim To investigate the causes,clinical classification and prognosis of drug induced liver injury. Methods Drug induced liver injury used as Key words, case analysis literatures on drug induced liver injury from 2001 to 2011 Chinese periodical full-text database were searched ,downloaded and gender,age, drugs,characters,clinical classifications and prognosis data were recorded. Results Among the recorded information,there were 4 737( 50.6% )male and 4 548( 49.0% ) female,age ranging from 5 months to 92 years old with the average(42.3 ± 13.1 )years. Drugs of Chinese herbs, antituberculotics, antibiotics, and anti hyperthyroidism drugs and antineoplastics were 1 979( 21.15% ), 1 898( 20.29% ), 1 135( 12.13% ),740( 7.91% ), 662( 7.07% ), and 382( 4.08% )patients respectively. 5 005( 62.73% )cases were classified to hepatocellular type,2 039( 23.84% )cases cholestasis type and 1 508( 17.63% )cases mixed type. As for the prognosis,8 144( 95.23% )cases cured or improved well,604( 6.90% )cases no change or worse to dead. Conclusion It is reported in China that drug induced liver injury occurred egually in males and females. Chinese herbs antituberculotics, non-steroid anti-inflammatory drugs antibiotics, anti-hyperthyroidism drugs, and the common hepatic injury was hepatocyte injury. Most patients were hepatocellular and generally the prognosis is good.%@@ 心肺复苏(Cardiopulmonary Resuscitation,简称CPR)的历史和人类的历史几乎一样悠久[1];早在1700多年前的东汉时期,名医张仲景在中就已经提到复苏方法:"救自缢死…上下安被卧之,一人以手按据胸上,数动之…"."安被卧之"是指平卧位,"以手按据胸上,数动之"是指连续胸外按压,这应该是世界上最早有关心肺复苏的详细描述.晋代葛洪所著的中写到:"塞两鼻孔,以芦管内其口中至咽,令人嘘之."

  14. New microRNA Biomarkers for Drug-Induced Steatosis and Their Potential to Predict the Contribution of Drugs to Non-alcoholic Fatty Liver Disease

    Science.gov (United States)

    López-Riera, Mireia; Conde, Isabel; Tolosa, Laia; Zaragoza, Ángela; Castell, José V.; Gómez-Lechón, María J.; Jover, Ramiro

    2017-01-01

    Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis. Methods: Human HepG2 cells were treated with drugs and changes in miRNA levels were measured by microarray and qRT-PCR. Drug-induced fat accumulation in HepG2 was analyzed by high-content screening and enzymatic methods. miRNA biomarkers were also analyzed in the sera of 44 biopsy-proven NAFLD patients and in 10 controls. Results: We found a set of 10 miRNAs [miR-22-5p, -3929, -24-2-5p, -663a, -29a-3p, -21 (5p and 3p), -27a-5p, -1260 and -202-3p] that were induced in human HepG2 cells and secreted to the culture medium upon incubation with model steatotic drugs (valproate, doxycycline, cyclosporin A and tamoxifen). Moreover, cell exposure to 17 common drugs for NAFLD patients showed that some of them (e.g., irbesartan, fenofibrate, and omeprazole) also induced these miRNAs and increased intracellular triglycerides, particularly in combinations. Finally, we found that most of these miRNAs (60%) were detected in human serum, and that NAFLD patients under fibrates showed both induction of these miRNAs and a more severe steatosis grade. Conclusion: Steatotic drugs induce a common set of hepatic miRNAs that could be used in drug screening during preclinical development. Moreover, most of these miRNAs are serum circulating biomarkers that could become useful in the diagnosis of iatrogenic steatosis. PMID:28179883

  15. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  16. 精神药物所致口吃的识别与处理%Identification and treatment of psychotropic drug-induced mental stuttering

    Institute of Scientific and Technical Information of China (English)

    付云婕

    2015-01-01

    Stuttering was a rare adverse reactions of psychotropic substances,in order to raise awareness of clinicians,the definition and classification of stuttering,diagnosis of drug-induced stuttering,pathogenesis and treatment were reviewed by this paper.%口吃是精神药物罕见的不良反应,为了提高临床医师的认识,本文对口吃的定义及分类、精神药物所致口吃的诊断、发病机制及处理等作一综述。

  17. Ultrastructure of developmental stages of Hemolivia mariae (Apicomplexa: Haemogregarinidae), natural parasite of the Australian sleepy lizard, in experimentally infected deviant hosts.

    Science.gov (United States)

    Paperna, I; Smallridge, C J

    2001-01-01

    Mabuya vitatta (Olivier) (Scincidae) and Agama stellio (L.) (Agamidae) were infected with Hemolivia mariae Smallridge et Paperna, 1997 by ingestion of tick viscera from Amblyomma limbatum Neumann, fed as nymphs on naturally infected Australian sleepy lizards, Tiliqua rugosa Gray. The unnatural infection apparently interfered with the developmental schedule of the parasites. Transmission electron microscopic images of merogonic stages were obtained, as well as images of early developing gametocytes. Tissue and intraerythrocytic meronts were bound by a hardened wall. Intraerythrocytic gametocytes were lodged in a parasitophorous vacuole, which was filled with granular material, and were bound by a two-membrane wall. Small and large osmiophilic bodies were located in a sub-pellicular position. With differentiation, the wall membranes tightened with the parasitophorous vacuole wall, and the osmiophilic bodies disappeared. The outer parasite membrane consolidated into a thick encasing with distinct sutures. Late infection in A. stellio comprised gametocytes only.

  18. Aggravation of excessive daytime sleepiness concurrent with aggravation of an injured ascending reticular activating system in a patient with mild traumatic brain injury

    Science.gov (United States)

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2017-01-01

    Abstract Background: We report on a patient who developed aggravation of excessive daytime sleepiness (EDS) concurrent with aggravation of an injured ascending reticular activating system (ARAS) following mild traumatic brain injury (TBI), demonstrated by follow-up diffusion tensor tractographies (DTTs). Methods: A 42-year-old male patient experienced head trauma resulting from flexion-hyperextension injury after collision with another vehicle from behind while stopped at an intersection. The patient lost consciousness for approximately 10 seconds and experienced no post-traumatic amnesia following the accident. The patient's Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain MRI performed at 10 weeks after onset. The patient complained of EDS after the head trauma and aggravation of EDS with passage of time. The Epworth Sleepiness Scale indicated abnormality with a score of 12 at 10 weeks after onset (cut-off: 10 points full mark: 24 score) and it was aggravated with a score of 18 at 16 months. Results: On 10-week DTT, decreased neural connectivity of the intralaminar thalamic nucleus to the prefrontal cortex and basal forebrain was observed in both hemispheres. However, no significant abnormality was observed in the dorsal and ventral lower ARAS. On 16-month DTT, the upper portion of the left dorsal lower ARAS showed partial tearing and the ventral lower ARAS showed thinning (both sides) and partial tearing (right side). Conclusions: Aggravation of EDS concurrent with aggravation of an injured ARAS was demonstrated in a patient with mild TBI using DTT. PMID:28121943

  19. Drug-induced hypotension SEP test and acetazolamide test using sup 133 Xe SPECT in patients with occlusive carotid disease; Selection of candidates for extracranial-intracranial bypass

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Satoshi; Kamiyama, Hiroyasu; Abe, Hiroshi; Takigawa, Shugo (Hokkaido Univ., Sapporo (Japan). School of Medicine); Mitsumori, Kenji; Nomura, Mikio; Saitoh, Hisatoshi

    1991-01-01

    The correlation between the drug-induced hypotension somatosensory evoked potential (SEP) test and regional cerebral blood flow changes after acetazolamide administration was studied. Fourteen patients presenting with transient ischemic attack, reversible ischemic neurological deficits, or minor completed stroke were evaluated. All patients had no or only localized low-density areas on computed tomographic scans, and unilateral occlusion or severe stenosis of the internal carotid or middle cerebral artery on cerebral angiograms. The Diamox asymmetry enhancement (DAE) was studied to detect reduced cerebral perfusion reserve in the affected hemispheres. The DAE was 7.9+-5.8% in seven patients positive in the SEP test, significantly higher than -1.5+-2.9% in patients negative in the SEP test. Postoperative SEP tests were negative in all five patients who underwent extracranial-intracranial (EC-IC) bypass surgery, suggesting that the EC-IC bypass improved the cerebral perfusion reserve in the affected hemispheres. The DAE decreased significantly in four of these patients. This study disclosed a significant correlation between the drug-induced hypotension SEP test and DAE. These parameters are considered important for evaluating patients with hemodynamic compromise and/or suitable candidates for EC-IC bypass. (author).

  20. DMH1 (4-[6-(4-isopropoxyphenylpyrazolo[1,5-a]pyrimidin-3-yl]quinoline inhibits chemotherapeutic drug-induced autophagy

    Directory of Open Access Journals (Sweden)

    Yue Sheng

    2015-07-01

    Full Text Available Our previous work found that DMH1 (4-[6-(4-isopropoxyphenylpyrazolo [1,5-a]pyrimidin-3-yl]quinoline was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II (CDDP-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.

  1. 精神药物所致咳嗽的识别与处理%Identification and Treatment of Psychotropic Drug-induced Cough

    Institute of Scientific and Technical Information of China (English)

    于相芬; 孙振晓

    2014-01-01

    Many psychotropic drugs could cause cough which may have no typical symptoms and is difficult to distinguish at an early stage. In order to make a better understanding of psychotropic drug-induced cough, this article made a review on the definition and causes of cough, and the diagnosis, differential diagnosis, pathomechanism and management of psychotropic drug-induced cough. Clinicians should strengthen the ability of discrimination and treatment of cough induced by psychotropic drugs.%多种精神药物可引起咳嗽,且表现无典型特征,早期难以发现。本文对咳嗽的定义及原因、精神药物所致咳嗽的诊断、鉴别诊断、发病机制及处理等作一综述。临床应加强对精神药物引起的咳嗽进行识别和处理。

  2. Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity.

    Science.gov (United States)

    Zhang, J D; Berntenis, N; Roth, A; Ebeling, M

    2014-06-01

    Gene signatures of drug-induced toxicity are of broad interest, but they are often identified from small-scale, single-time point experiments, and are therefore of limited applicability. To address this issue, we performed multivariate analysis of gene expression, cell-based assays, and histopathological data in the TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system) database. Data mining highlights four genes-EGR1, ATF3, GDF15 and FGF21-that are induced 2 h after drug administration in human and rat primary hepatocytes poised to eventually undergo cytotoxicity-induced cell death. Modelling and simulation reveals that these early stress-response genes form a functional network with evolutionarily conserved structure and intrinsic dynamics. This is underlined by the fact that early induction of this network in vivo predicts drug-induced liver and kidney pathology with high accuracy. Our findings demonstrate the value of early gene-expression signatures in predicting and understanding compound-induced toxicity. The identified network can empower first-line tests that reduce animal use and costs of safety evaluation.

  3. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology

    DEFF Research Database (Denmark)

    Graff, Claus; Andersen, Mads P; Xue, Joel Q

    2009-01-01

    BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...

  4. 畸形子宫早孕药物流产的临床观察%Clinical Observation on Drug Induced Abortion in Abnormal Uterine Pregnancy

    Institute of Scientific and Technical Information of China (English)

    赵童; 张立红

    2016-01-01

    Objective:To investigate the clinical effect of drug induced abortion in abnormal uterine preg-nancy (the uterine septum,uterus bicornis,bicorbate uterus and uterus unicornis).Methods:37 patients with abnormal uterine pregnancy received drug induced abortion (mifepristone combined with misoprostol) termination of pregnancy.Results:Among the 37 patients,28 patients were complete abortion,8 patients were incomplete abortion,1 case was abortion failure.Incomplete abortion and abortion failure patients un-derwent curettage,the postoperative course was uneventful,no accidents such as uterine perforation or suc-tion leaks occurred.The complete abortion rate was 75.7%,the curettage rate was 24.3%.Conclusion:The success rate of drug induced abortion in abnormal uterine pregnancy is high,and for incomplete abortion and medical abortion failure patients,because early drug effects enable embryo stripping,uterine contraction ex-trusion blastocyst and uterine luminal contents of depression or partial discharge,it can effectively reduce the risk of abortion.%目的::针对药物流产终止畸形子宫(子宫纵隔、双角子宫及鞍状子宫、单角子宫)早孕的临床效果展开探讨。方法:37名畸形子宫早孕患者用药物流产(米非司酮联合米索前列醇口服)终止妊娠。结果:37名患者中完全流产28名,未完全流产8名,流产失败1名。而后为不全流产及流产失败患者均行清宫术,手术过程顺利,未产生子宫穿孔、漏吸等情况。完全流产率为75.7%,清宫率为24.3%。结论:畸形子宫早孕应用药物流产成功概率较高,对不全流产及药流失败者因前期药物作用使胚胎剥离,子宫收缩挤压胚囊及宫腔内容物下移或部分排出,可有效降低清宫术的风险。

  5. Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y; Löscher, Wolfgang

    2014-01-01

    P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

  6. A Framework of Knowledge Integration and Discovery for Supporting Pharmacogenomics Target Predication of Adverse Drug Events: A Case Study of Drug-Induced Long QT Syndrome.

    Science.gov (United States)

    Jiang, Guoqian; Wang, Chen; Zhu, Qian; Chute, Christopher G

    2013-01-01

    Knowledge-driven text mining is becoming an important research area for identifying pharmacogenomics target genes. However, few of such studies have been focused on the pharmacogenomics targets of adverse drug events (ADEs). The objective of the present study is to build a framework of knowledge integration and discovery that aims to support pharmacogenomics target predication of ADEs. We integrate a semantically annotated literature corpus Semantic MEDLINE with a semantically coded ADE knowledgebase known as ADEpedia using a semantic web based framework. We developed a knowledge discovery approach combining a network analysis of a protein-protein interaction (PPI) network and a gene functional classification approach. We performed a case study of drug-induced long QT syndrome for demonstrating the usefulness of the framework in predicting potential pharmacogenomics targets of ADEs.

  7. CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic Drug-Induced Side Effects.

    Science.gov (United States)

    Ivanova, S A; Filipenko, M L; Vyalova, N M; Voronina, E N; Pozhidaev, I V; Osmanova, D Z; Ivanov, M V; Fedorenko, O Yu; Semke, A V; Bokhan, N A

    2016-03-01

    Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

  8. Drug-Induced QT Prolongation as a Result of an Escitalopram Overdose in a Patient with Previously Undiagnosed Congenital Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    Paul Singh

    2014-01-01

    Full Text Available We present a case of drug-induced QT prolongation caused by an escitalopram overdose in a patient with previously undiagnosed congenital LQTS. A 15-year-old Caucasian female presented following a suicide attempt via an escitalopram overdose. The patient was found to have a prolonged QT interval with episodes of torsades de pointes. The patient was admitted to the telemetry unit and treated. Despite the resolution of the torsades de pointes, she continued to demonstrate a persistently prolonged QT interval. She was seen by the cardiology service and diagnosed with congenital long QT syndrome. This case illustrates the potential for an escitalopram overdose to cause an acute QT prolongation in a patient with congenital LQTS and suggests the importance of a screening electrocardiogram prior to the initiation of SSRIs, especially in patients at high risk for QT prolongation.

  9. Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes to drug-induced diarrhea.

    Science.gov (United States)

    Moon, Changsuk; Zhang, Weiqiang; Ren, Aixia; Arora, Kavisha; Sinha, Chandrima; Yarlagadda, Sunitha; Woodrooffe, Koryse; Schuetz, John D; Valasani, Koteswara Rao; de Jonge, Hugo R; Shanmukhappa, Shiva Kumar; Shata, Mohamed Tarek M; Buddington, Randal K; Parthasarathi, Kaushik; Naren, Anjaparavanda P

    2015-05-01

    Diarrhea is one of the most common adverse side effects observed in ∼7% of individuals consuming Food and Drug Administration (FDA)-approved drugs. The mechanism of how these drugs alter fluid secretion in the gut and induce diarrhea is not clearly understood. Several drugs are either substrates or inhibitors of multidrug resistance protein 4 (MRP4), such as the anti-colon cancer drug irinotecan and an anti-retroviral used to treat HIV infection, 3'-azido-3'-deoxythymidine (AZT). These drugs activate cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluid secretion by inhibiting MRP4-mediated cAMP efflux. Binding of drugs to MRP4 augments the formation of MRP4-CFTR-containing macromolecular complexes that is mediated via scaffolding protein PDZK1. Importantly, HIV patients on AZT treatment demonstrate augmented MRP4-CFTR complex formation in the colon, which defines a novel paradigm of drug-induced diarrhea.

  10. Is the drug-induced hypersensitivity syndrome (DIHS due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

    Directory of Open Access Journals (Sweden)

    Borgia Guglielmo

    2010-03-01

    Full Text Available Abstract Background Drug-Induced Hypersensitivity Syndrome (DIHS is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug. We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. Case presentation We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6 DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die that was tapered very slowly. The patient recovered completely. Conclusions The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.

  11. Excessive daytime sleepiness in Campo Grande general population, Brazil Sonolência diurna excessiva na população geral de Campo Grande, MS

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    José Carlos Souza

    2002-09-01

    Full Text Available The prevalence of excessive daytime sleepiness (EDS in general population was determined by means of 408 home interviews of adults, in a representative sample of Campo Grande city, Brazil. The random sample was stratified by sex, age and economic social status. EDS was considered in those with indexes 11 or more in the Epworth Sleepiness Scale. Statistics used chi-square, Fisher and Pearson tests; and inferences based on binomial distribution parameters; the significance level was 5% and confidence interval (CI was 95%. The prevalence of EDS was 18.9% of the general population ( SD=1.9%; CI 15.1% to 22.7%. No significant association was found between EDS and the use of hypnotics, nor with insomnia, body mass index, sex, age, years of schooling, economic social status, marital status, occupation and the use of alternative means to improve sleep. When the sample was separated according to sex, only the male group showed significant association between EDS and actual insomnia (p=0.005.Buscou-se a prevalência da sonolência diurna excessiva (SDE com 408 entrevistas domiciliares de adultos, em amostra representativa da população geral da cidade de Campo Grande, MS. A amostragem aleatória foi estratificada por sexo, idade e classe social. Tinham SDE as pessoas com 11 ou mais pontos na Escala de Sonolência Epworth. Usaram-se os testes de qui-quadrado, Fisher, Pearson e inferências com base nos parâmetros da distribuição binomial; nível de significância 5% e intervalo de confiança (IC 95%. Tinham SDE 18,9% da população (dp=1,9%; IC 15,1% a 22,7%; não houve associação significativa entre SDE e uso de hipnóticos, nem insônia, índice de massa corporal, sexo, idade, escolaridade, classe sócio-econômica, estado civil, ocupação e uso de meios alternativos para dormir melhor. Ao serem separados de acordo com sexo, apenas no sexo masculino houve associação significativa entre SDE e presença de insônia (p=0,005.

  12. Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy.

    Science.gov (United States)

    Mitler; Harsh; Hirshkowitz; Guilleminault

    2000-07-01

    Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of two 9-week, double-blind, placebo-controlled, multicenter, clinical trials of modafinil were enrolled in two 40-week, open-label, extension studies. A flexible-dose regimen (i.e. 200, 300, or 400 mg daily) was followed in one study. In the second study, patients received 200 mg/day for 1 week, followed by 400 mg/day for 1 week. Investigators then prescribed either 200- or 400-mg doses for the duration of the study. Efficacy was evaluated using Clinical Global Impression of Change (CGI-C) scores, the Epworth Sleepiness Scale (ESS), and the 36-item Medical Outcomes Study health survey (SF-36). Adverse events were recorded. Data from the two studies were combined.Results: The majority of patients ( approximately 75%) received 400 mg of modafinil daily. Disease severity improved in >80% of patients throughout the 40-week study. At weeks 2, 8, 24, and 40, disease severity was 'much improved' or 'very much improved' in 49, 58, 59, and 58% of patients, respectively. The mean (+/-SEM) ESS score improved significantly from 16.5+/-0.2 at open-label baseline to 12.4+/-0.2 at week 2 and remained at that level through week 40 (PQuality of life scores at weeks 4, 8, 24, and 40 were significantly improved versus open-label baseline scores for six of the eight SF-36 domains (P<0.001). The most common treatment-related adverse events were headache (13%), nervousness (8%), and nausea (5%). Most adverse events were mild to moderate in nature. A total of 341 patients (71%) completed the studies. Forty-three patients (9.0%) discontinued treatment because of

  13. Armodafinil and modafinil in patients with excessive sleepiness associated with shift work disorder: a pharmacokinetic/pharmacodynamic model for predicting and comparing their concentration-effect relationships.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Ezzet, Farkad

    2012-09-01

    Armodafinil, the longer lasting R-isomer of racemic modafinil, improves wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD). Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses. Pooled Multiple Sleep Latency Test (MSLT) data from 2 randomized, double-blind, placebo-controlled trials in 463 patients with SWD, 1 with armodafinil 150 mg/d and 1 with modafinil 200 mg/d (both administered around 2200 h before night shifts), were used to build a pharmacokinetic/pharmacodynamic model. Predicted plasma drug concentrations were obtained by developing and applying a population pharmacokinetic model using nonlinear mixed-effects modeling. Armodafinil 200 mg produced a plasma concentration above the EC(50) (4.6 µg/mL) for 9 hours, whereas modafinil 200 mg did not exceed the EC(50). Consequently, armodafinil produced greater increases in predicted placebo-subtracted MSLT times of 0.5-1 minute (up to 10 hours after dosing) compared with modafinil. On a milligram-to-milligram basis, armodafinil 200 mg consistently increased wakefulness more than modafinil 200 mg, including times late in the 8-hour shift.

  14. 药物诱发自身免疫性肝炎的研究进展%Progress of drug-induced autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    陈慧; 郑聘聘; 王炳元

    2011-01-01

    More and more cases of drug-induced liver injury have been reported. Drug-induced autoimmune hepatitis (DI-AIH) may occur because some drugs or its metabolites may bind to a hepatocyte surface protein, forming a neoantigen and activating autoimmune reaction, and/or due to such factors as genetic susceptibility, female and advanced age, etc. The symptoms of DIAIH are often concealed, but a few DIAIH patients can develop liver failure rapidly. Significant increase in biliary enzyme levels and disorder of bilirubin metabolism are general manifestations, while AST and ALT may elevate moderately. Unlike AIH, the autoantibodies in DIAIH patinets can change to be negative with disease improvement. In radiological findings, DIAIH usually presents with lobe liver atrophy, delayed-phase images, and few can develop cirrhosis. Diagnosis depends on the roussel uclaf causality assessment method (RUCAM) and clinical diagnostic scale (modified RUCAM). Good response to corticosteroids (CS) treatment is also an important prognostic factor. Complete remission in 1 -3 months and no relapse after withdrawal of CS mean fine prognosis. DIAIH is an a-cute auto-limit disease, and has a good outcome if diagnosis and treatment are given correctly and promptly.%随着药物(或中草药、保健品)的滥用和“被用”,药物性肝损害不断增加.某些药物本身或代谢产物可与蛋白结合形成半抗原,刺激机体发生免疫反应,和(或)由于宿主的遗传易感性、女性、高龄等因素,导致药物诱发自身免疫性肝炎( drug-induced autoimmune hepatitis,DIAIH)的发生.DIAIH的临床症状多数隐匿,但也可迅速发展致肝衰竭.一般表现为胆道酶增加和胆红素排泄障碍,AST和ALT通常为中等度升高.自身抗体的出现与AIH相似,但随着疾病的好转迅速转阴.影像学上DIAIH可见明显的肝叶萎缩、门脉期强化和造影剂排泄延迟,多数不发展至肝硬化.诊断包括因果关系评估方法(roussel uclaf

  15. Construct validity and factor structure of the pittsburgh sleep quality index and epworth sleepiness scale in a multi-national study of African, South East Asian and South American college students.

    Directory of Open Access Journals (Sweden)

    Bizu Gelaye

    Full Text Available The Pittsburgh Sleep Quality Index (PSQI and the Epworth Sleepiness Scale (ESS are questionnaires used to assess sleep quality and excessive daytime sleepiness in clinical and population-based studies. The present study aimed to evaluate the construct validity and factor structure of the PSQI and ESS questionnaires among young adults in four countries (Chile, Ethiopia, Peru and Thailand.A cross-sectional study was conducted among 8,481 undergraduate students. Students were invited to complete a self-administered questionnaire that collected information about lifestyle, demographic, and sleep characteristics. In each country, the construct validity and factorial structures of PSQI and ESS questionnaires were tested through exploratory and confirmatory factor analyses (EFA and CFA.The largest component-total correlation coefficient for sleep quality as assessed using PSQI was noted in Chile (r = 0.71 while the smallest component-total correlation coefficient was noted for sleep medication use in Peru (r = 0.28. The largest component-total correlation coefficient for excessive daytime sleepiness as assessed using ESS was found for item 1 (sitting/reading in Chile (r = 0.65 while the lowest item-total correlation was observed for item 6 (sitting and talking to someone in Thailand (r = 0.35. Using both EFA and CFA a two-factor model was found for PSQI questionnaire in Chile, Ethiopia and Thailand while a three-factor model was found for Peru. For the ESS questionnaire, we noted two factors for all four countries.Overall, we documented cross-cultural comparability of sleep quality and excessive daytime sleepiness measures using the PSQI and ESS questionnaires among Asian, South American and African young adults. Although both the PSQI and ESS were originally developed as single-factor questionnaires, the results of our EFA and CFA revealed the multi- dimensionality of the scales suggesting limited usefulness of the global PSQI and ESS

  16. 药物性血尿52例临床分析%Clinical analysis of 52 cases of drug-induced hematuria

    Institute of Scientific and Technical Information of China (English)

    叶惠尧; 温小春

    2009-01-01

    Objective:To explore the cause of drug-induced hematuria. Methods:To analyse for clinical information of 52 cases of drug-induced hematuria in the data and reason. Results:The drugs causing hematuria were sulfa drugs, diclofenac, indocin, centamyein, cefradine, cefletin, ciprofloxacin, oflxaein and amethopterin.These patients had historical to use related drugs. Clinical maniteslations: hematufia, cryslats by microscopic examination of uria, skin rash in a small mumber of patients. Old people were more (51.92%) in these patients. All patients were fully recovered by stoping drugs and symptomatic treatment. All patients recovered not recured by following and visiting them at six months. Conclusion:In order to avoid occurrence of the disease, clinical doctors should master strictly medication indications and prevent to abuse drugs and try to use fewer or no drugs of nephrotoxicity particularly in elderly patients and educate patients to use drugs under the guidance of doctor as much as possible and no blind.%目的:探讨药物所致血尿的病因.方法:对52例药物性血尿的临床资料进行数理分析.结果:表明引起血尿的药物有磺胺类、双氯酚酸、消炎痛、庆大霉素、头孢拉啶、头孢氨苄、环丙沙星、氧氟沙星、甲氨蝶呤.患者有使用相关药物史,临床表现为血尿,镜检尿液有结晶体,少数患者有皮疹,老年患者较多(51.9%).停用药物及对症处理后痊愈.随访6个月无复发.结论:为避免该症的发生,临床医生应严格掌握用药指征,防止滥用药物,尽量少用或不用肾毒性药物,特别是老年患者,并教育患者应尽可能在医生指导下用药、不要盲目用药.

  17. 药物致Q-T间期延长的文献分析%Literature Analysis of Drug-induced Q-T Interval Prolongation

    Institute of Scientific and Technical Information of China (English)

    穆维静; 任晓蕾; 张海英

    2013-01-01

    近年来,临床实践有许多药物都会导致Q-T间期延长甚至尖端扭转型室性心律失常(TdP)。本文通过对1979年-2013年国内医药期刊公开报道的药物致Q-T间期延长的个案进行统计和分析,总结了56个病例的一般情况、引起Q-T间期延长的药物、发生时间及转归等,致Q-T间期延长药物中排在前三位的分别为抗心律失常药、抗微生物药、抗组胺药。大部分患者在用药后一个月内出现,停药及对症治疗后好转。临床医师应正确地认识药物致Q-T间期延长发生机制和易感因素,才能保证临床安全有效地使用药物。%Many medications can cause QT prolongation and torsades de pointes ventricular tachycardia (TdP), which were gradually discovered in recent years. Based on year 1979-2013 domestic medical journals and public report about drug-induced QT prolongation were collected and analyzed. Total of 56 cases were collected and summarized in respect of general condition of patients, drugs involved, occurrence times of ADR, outcomes and so on. The top three classes of drugs causing Q-T interval prolongation are antiarrhythmic drugs, antimicrobials and antihistamines. Most ADRs occurred within one month after treatment. ADRs relieved after drug withdrawal and symptomatic treatment. Physicians should pay more attention to the medications’ mechanisms and risk factors of drug-induced Q-T interval prolongation to ensure medication administration safety.

  18. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

    2014-09-15

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  19. Expression of Integrins in Drug-induced Gingival Overgrowth%整合素在药物性牙龈增生中的表达研究

    Institute of Scientific and Technical Information of China (English)

    周洁

    2012-01-01

    Objective: To investigate the possible correlation between integrin al , a2 and (31 expression and excessive collagen synthesis in fibroblasts from drug-induced gingival overgrowth (DIGO) patients. Methods: Gingival fibroblasts from five DIGO patients and five healthy subjects were included. The expression of al, a2 and (31 integrin subunits was examined by immunohistochemistry and quantitative PCR. Results: Our results demonstrate that the expression of al was significantly lower in HGF fibroblasts compared with control fibroblasts (P<0. 01). No significant differences in the expression of a2 and (31 were detected. Conclusion: The decreased expression of integrin al in DIGO fibroblasts may be related to the excessive collagen deposition in DIGO patients.%目的:检测整合素α1、α2和β1在来源于药物性牙龈增生(drug-induced gingival overgrowth,DIGO)患者的牙龈成纤维细胞中的表达水平变化,探讨其与DIGO胶原聚集的相关性.方法:采用免疫组织化学法和实时定量PCR分别检测整合素α1、α2和β1在来源于DIGO和正常人群牙龈组织和成纤维细胞中的表达水平.结果:整合素α1在DIGO牙龈成纤维细胞中的表达水平显著性低于其在正常牙龈成纤维细胞中的表达水平(P<0.01).而整合索α2和β1在2组牙龈成纤维细胞中的表达水平无显著性差异.结论:整合素α1在DIGO牙龈成纤维细胞中的低表达可能与胶原聚集相关.

  20. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    Directory of Open Access Journals (Sweden)

    Singh JP

    2004-08-01

    Full Text Available Abstract Background Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. Methods 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio. Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was

  1. Experimental evaluation of prophylactic and curative effect of a herbal drug Hemidesmus indicus R.Br. in drug induced ulcers in wistar albino rats

    Directory of Open Access Journals (Sweden)

    Shishira Bharadwaj

    2013-06-01

    Full Text Available Peptic Ulcers are the most common condition experienced by most of the people due to urbanized lifestyle. Hemidesmus indicus R.Br. is a herbal drug mentioned for its treatment in the ancient Indian traditional medicine. To compare the Prophylactic and Curative effects of aqueous and Alcoholic extracts of Hemidesmus indicus in Drug induced ulcers. Aqueous and Alcoholic extracts of the drug were studied for their ulcer healing activity in Wistar Albino rats. Ninety Wistar albino rats were divided into nine groups with one control, four prophylactic and four curative groups. Ulcers were induced with Indomethacin in a dose of 20 mg/kg body weight twice in a gap of 15 hours. Aqueous extract was given in a dose of 500 mg/kg body weight and alcohol in a dose of 100 mg/kg body weight. It was found that both have potential ulcer healing activity with alcoholic extract marginally better than aqueous extract. It can thus be concluded that Hemidesmus indicus R. Br is a effective drug in peptic ulcers. [Int J Res Med Sci 2013; 1(3.000: 243-247

  2. Clinical features and {sup 123}I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Sanz-Viedma, Salome [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Garcia-Solis, David [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, Pablo [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Hospital Universitario Virgen del Rocio, Unidad de Trastornos del Movimiento. Servicio de Neurologia, Seville (Spain)

    2010-03-15

    To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 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<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 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 {sup 123}I-FP-CIT SPECT imaging. (orig.)

  3. Comparison of Liver Biopsy Findings with the Digestive Disease Week Japan 2004 Scale for Diagnosis of Drug-Induced Liver Injury.

    Science.gov (United States)

    Tsutsui, Akemi; Nakanuma, Yasuni; Takaguchi, Kouichi; Nakamura, Satoko; Shibata, Hiroshi; Baba, Nobuyuki; Senoh, Tomonori; Nagano, Takuya; Ikeda, Hiroko

    2015-01-01

    The liver biopsy remains a valuable tool in the diagnosis of drug-induced liver injury (DILI). The Digestive Disease Week Japan 2004 (DDW-J) scale proposed as an objective tool for the diagnosis of DILI has been widely used in Japan. So far, the histological features have not been compared with DDW-J scale in detail. Herein, we examined the correlation between liver biopsy findings and clinical features, particularly DDW-J scales. A total of 80 patients with liver injuries of unknown cause were enrolled. Based on the histological findings, these cases were categorized into 3 groups: A (DILI was strongly suspected), B (DILI was suspected), and C (DILI should be considered in the differential diagnosis). Histological groups and DDW-J scale were moderately correlated (κ = 0.60). The mean total DDW-J scale scores were as follows: 4.89 for A, 3.26 for B, and 0.75 for C (p biopsy findings and DDW-J scale were well correlated, and the hepatocellular type of liver injuries was well coincided by both evaluations, though there were several discrepant cases, particularly in cholestatic type.

  4. Research advances in drug-induced autoimmune hepatitis%药物诱导的自身免疫性肝炎研究进展

    Institute of Scientific and Technical Information of China (English)

    李春敏; 张静怡; 唐颖悦; 茅益民

    2016-01-01

    Drug induced autoimmune hepatitis (DIAIH) refers to the liver injury mediated by druginduced autoimmune reaction.Since it has similar clinical features as idiopathic autoimmune hepatitis,it is often difficult to make differential diagnosis in clinical practice.A deep understanding of the development,pathogenesis,related drugs,risk factors,and clinical and histological features of DIAIH helps with the correct diagnosis and treatment of DIAIH.%药物诱导的自身免疫性肝炎是由药物诱发的自身免疫反应所介导的肝损伤,由于与特发性自身免疫性肝炎的临床特征相似,临床上鉴别诊断往往非常困难.深入了解药物诱导的自身免疫性肝炎的发生情况、发病机制、所涉及的相关药物、风险因素、临床和组织学特点等,有助于更好地正确诊断和治疗本病.

  5. NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis.

    Science.gov (United States)

    Yuliwulandari, Rika; Susilowati, Retno Wilujeng; Wicaksono, Britanto Dani; Viyati, Kencono; Prayuni, Kinasih; Razari, Intan; Kristin, Erna; Syafrizal; Subagyo; Sri Diana, Eva; Setiawati, Suci; Ariyani, Aziza; Mahasirimongkol, Surakameth; Yanai, Hideki; Mushiroda, Taisei; Tokunaga, Katsushi

    2016-06-01

    Drug-induced liver injury (DILI) is the most common adverse drug reaction in the treatment of tuberculosis (TB). Several studies showed that patients with TB and the slow-acetylator phenotype caused by NAT2 variants are highly susceptible to DILI caused by anti-TB drugs, hereafter designated AT-DILI. However, the role of NAT2 variants in AT-DILI has never been assessed for an Indonesian population. We recruited 50 patients with TB and AT-DILI and 191 patients with TB but without AT-DILI; we then used direct DNA sequencing to assess single-nucleotide polymorphisms in the coding region of NAT2. NAT2*6A was significantly associated with susceptibility to AT-DILI (P=7.7 × 10(-4), odds ratio (OR)=4.75 (1.8-12.55)). Moreover, patients with TB and the NAT2-associated slow-acetylator phenotype showed higher risk of AT-DILI than patients with the rapid- or intermediate-acetylator phenotypes (P=1.7 × 10(-4), OR=3.45 (1.79-6.67)). In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.

  6. Sleep Apnea, Sleep Debt and Daytime Sleepiness Are Independently Associated with Road Accidents. A Cross-Sectional Study on Truck Drivers

    Science.gov (United States)

    Guglielmi, Ottavia; Dini, Guglielmo; Bersi, Francesca; Fornarino, Stefania; Toletone, Alessandra; Chiorri, Carlo

    2016-01-01

    Background Recent research has found evidence of an association between motor vehicle accidents (MVAs) or near miss accidents (NMAs), and excessive daytime sleepiness (EDS) or its main medical cause, Obstructive Sleep Apnea (OSA). However, EDS can also be due to non-medical factors, such as sleep debt (SD), which is common among professional truck drivers. On the opposite side, rest breaks and naps are known to protect against accidents. Study Objectives To investigate the association of OSA, SD, EDS, rest breaks and naps, with the occurrence of MVAs and NMAs in a large sample of truck drivers. Methods 949 male truck drivers took part in a cross-sectional medical examination and were asked to complete a questionnaire about sleep and waking habits, risk factors for OSA and EDS. Results MVAs and NMAs were reported by 34.8% and 9.2% of participants, respectively. MVAs were significantly predicted by OSA (OR = 2.32 CI95% = 1.68–3.20), SD (OR = 1.45 CI95% = 1.29–1.63), EDS (OR = 1.73 CI95% = 1.15–2.61) and prevented by naps (OR = 0.59 CI95% = 0.44–0.79) or rest breaks (OR = 0.63 CI95% = 0.45–0.89). NMAs were significantly predicted by OSA (OR = 2.39 CI95% = 1.47–3.87) and SD (OR = 1.49 CI95% = 1.27–1.76) and prevented by naps (OR = 0.52 CI95% = 0.32–0.85) or rest breaks (OR = 0.49 CI95% = 0.29–0.82). Conclusions When OSA, SD or EDS are present, the risk of MVAs or NMAs in truck drivers is severely increased. Taking a rest break or a nap appear to be protective against accidents. PMID:27902703

  7. Aphrodisiac drug-induced hemolysis.

    Science.gov (United States)

    Stalnikowicz, Ruth; Amitai, Yona; Bentur, Yedidia

    2004-01-01

    Volatile alkyl nitrites have been used during the past decades for "recreational purposes," and for intensifying sexual experience. Their use has been associated with methemoglobinemia and hemolysis. We report three patients who presented over the past year with acute hemolysis after inhalation of butyl nitrite, two of them had glucose-6-phosphate dehydrogenase (G6PD) deficiency.

  8. Drug-induced lupus erythematosus

    Science.gov (United States)

    ... A chest x-ray may show signs of pleuritis or pericarditis (inflammation around the lining of the ... anti-inflammatory drugs (NSAIDs) to treat arthritis and pleurisy Corticosteroid creams to treat skin rashes Antimalarial drugs ( ...

  9. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are consid

  10. Influence of benzodiazepines on antiparkinsonian drug treatment in levodopa users

    NARCIS (Netherlands)

    van de Vijver, D A M C; Roos, R A C; Jansen, P A F; Porsius, A J; de Boer, A

    2002-01-01

    OBJECTIVES: Animal studies showed that benzodiazepines decrease the concentration of dopamine in the striatum. Benzodiazepines may therefore affect the treatment of Parkinson's disease. This study determined whether start of a benzodiazepine in patients on levodopa was followed by a faster increase

  11. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea.

    Science.gov (United States)

    De Corso, E; Bastanza, G; Della Marca, G; Grippaudo, C; Rizzotto, G; Marchese, M R; Fiorita, A; Sergi, B; Meucci, D; Di Nardo, W; Paludetti, G; Scarano, E

    2015-12-01

    Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 ± 2.8 versus 4.1 ± 2.2 (p DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as determined by the subject's initial AHI, but also by DISE findings combined with results of gentle mandibular advancement manoeuvre allowing direct view of the effects of mandibular protrusion on breathing spaces in obstruction sites, and showing good optimisation of

  12. Drug-induced sleep endoscopy and simulated snoring in patients with sleep-disordered breathing: agreement of anatomic changes in the upper airway.

    Science.gov (United States)

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

    2015-09-01

    Drug-induced sleep endoscopy (DISE) and simulated snoring (SimS) are performed as part of the diagnostic procedure in patients with suspected sleep-disordered breathing (SDB). Despite both techniques frequently performed, they have rarely been evaluated yet in terms of agreement of the obtained results. Both diagnostic procedures were performed consecutively in 40 patients with SDB and documented identically. The obtained data were analysed with respect to the agreement of both procedure at different levels of the oropharynx as well as different patterns of obstruction and vibration. The anterior-posterior collapsibility of the soft palate/uvula revealed a moderate agreement between SimS and DISE (κ = 0.42; 95 % CI 0.22-0.63). The dorsal shift of the tongue base agreed moderate for patients with an AHI below 10 (κ = 0.47) and above 25 (κ = 0.44) between SimS ad DISE. The lateral and circular pharyngeal collapsibility at velum and tongue base level did not agree between SimS and DISE, was higher for DISE and could be partially reversed by mandibular protrusion. Collapse patterns of the soft palate and uvula can be induced by SimS and resemble the patterns induced by DISE. The dorsalization of the tongue base can be simulated to a lower extent by SimS. Lateral and circular patterns of collapse at the upper and lower oropharynx induced by DISE do not seem to be simulated by SimS. SimS seems to be an additional method to screen the collapsibility of the soft palate and uvula prior to DISE.

  13. Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI).

    Science.gov (United States)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-03-01

    Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism based inhibition of ATP synthesis is exerted by diclofenac and its metabolites. Phase-I metabolite (4'-OH-Dic) and Phase-II metabolites (DicGluA and DicSG) showed potent inhibition (2-5 fold) of ATP synthesis, where as 5-OH-Dic, one of the Phase-I metabolite, was a less potent inhibitor as compared to Dic. The calculated kinetic constants of mechanism based inhibition of ATP synthesis by Dic showed maximal rate of inactivation (Kinact) of 2.64 ± 0.15 min(-1) and half maximal rate of inactivation (KI) of 7.69 ± 2.48 μM with Kinact/KI ratio of 0.343 min(-1) μM(-1). Co-incubation of mitochondria with Dic and reduced GSH exhibited a protective effect on Dic mediated inhibition of ATP synthesis. Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis.

  14. Integrated comparison of drug-related and drug-induced ultra performance liquid chromatography/mass spectrometry metabonomic profiles using human hepatocyte cultures.

    Science.gov (United States)

    Croixmarie, Vincent; Umbdenstock, Thierry; Cloarec, Olivier; Moreau, Amélie; Pascussi, Jean-Marc; Boursier-Neyret, Claire; Walther, Bernard

    2009-08-01

    approach coupled to a statistical pretreatment of the data, enabling the separate capture of both drug related and drug induced biomarkers, represents a powerful technique for future mechanistic studies using cellular tools.

  15. Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man.

    Science.gov (United States)

    Dragovic, Sanja; Vermeulen, Nico P E; Gerets, Helga H; Hewitt, Philip G; Ingelman-Sundberg, Magnus; Park, B Kevin; Juhila, Satu; Snoeys, Jan; Weaver, Richard J

    2016-12-01

    The current test systems employed by pharmaceutical industry are poorly predictive for drug-induced liver injury (DILI). The 'MIP-DILI' project addresses this situation by the development of innovative preclinical test systems which are both mechanism-based and of physiological, pharmacological and pathological relevance to DILI in humans. An iterative, tiered approach with respect to test compounds, test systems, bioanalysis and systems analysis is adopted to evaluate existing models and develop new models that can provide validated test systems with respect to the prediction of specific forms of DILI and further elucidation of mechanisms. An essential component of this effort is the choice of compound training set that will be used to inform refinement and/or development of new model systems that allow prediction based on knowledge of mechanisms, in a tiered fashion. In this review, we focus on the selection of MIP-DILI training compounds for mechanism-based evaluation of non-clinical prediction of DILI. The selected compounds address both hepatocellular and cholestatic DILI patterns in man, covering a broad range of pharmacologies and chemistries, and taking into account available data on potential DILI mechanisms (e.g. mitochondrial injury, reactive metabolites, biliary transport inhibition, and immune responses). Known mechanisms by which these compounds are believed to cause liver injury have been described, where many if not all drugs in this review appear to exhibit multiple toxicological mechanisms. Thus, the training compounds selection offered a valuable tool to profile DILI mechanisms and to interrogate existing and novel in vitro systems for the prediction of human DILI.

  16. Drug-Induced Liver Injury Associated With Antidepressive Psychopharmacotherapy: An Explorative Assessment Based on Quantitative Signal Detection Using Different MedDRA Terms.

    Science.gov (United States)

    Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J; Hiemke, Christoph; Schönfeldt-Lecuona, Carlos

    2016-06-01

    Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepress ants. We performed a quantitative signal detection analysis using data from the Uppsala Monitoring Centre from the WHO that records adverse drug reaction (ADR) data from worldwide sources; we retrieved substance- and country-specific (Australia, France, Germany, Italy, Spain, the United Kingdom, and the United States) ADR data and calculated reporting odds ratios as measures for disproportionality within a case/noncase approach. To allow for identification of agents that cause severe forms of hepatotoxic ADRs, we used 2 terms of the MedDRA ("drug-related hepatic disorders-comprehensive search" [DRHD-CS] and "… -severe events only" [DRHD-SEO]). Distribution of signals was heterogeneous throughout the different data sets, and consistent findings were present for only a few substances: agomelatine (AGM) and tianeptine as well as both positive control agents (amineptine, nefazodone) generated signals related to DRHD-CS and DRHD-SEO in all analyzed data sets. Tri- and tetracyclic antidepressants (here amitriptyline, clomipramine, mianserin, mirtazapine, trimipramine) were associated with hepatotoxicity in several data sets. Using 2 MedDRA terms did not allow for detection of agents that cause severe hepatotoxic ADR. Our results support the findings of previous, primarily literature-based, systematic analyses of hepatotoxicity related to antidepressive psychopharmacotherapy. No new safety information could be generated. Application of 2 MedDRA terms did not increase the substance-specific safety information.

  17. Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect

    Directory of Open Access Journals (Sweden)

    Meng Yan

    2016-09-01

    Full Text Available Diastereoisomers of quinidine and quinine are used to treat arrhythmia and malaria, respectively. It has been reported that both drugs block the hERG (human ether-a-go-go-related gene potassium channel which is essential for myocardium repolarization. Abnormality of repolarization increases risk of arrhythmia. The aim of our research is to study and compare the impacts of quinidine and quinine on hERG. Results show that both drugs block the hERG channel, with quinine 14-fold less potent than quinidine. In addition, they presented distinct impacts on channel dynamics. The results imply their stereospecific block effect on the hERG channel. However, F656C-hERG reversed this stereoselectivity. The mutation decreases affinity of the two drugs with hERG, and quinine was more potent than quinidine in F656C-hERG blockage. These data suggest that F656 residue contributes to the stereoselective pocket for quinidine and quinine. Further study demonstrates that both drugs do not change hERG protein levels. In rescue experiments, we found that they exert no reverse effect on pentamidine- or desipramine-induced hERG trafficking defect, although quinidine has been reported to rescue trafficking-deficient pore mutation hERG G601S based on the interaction with F656. Our research demonstrated stereoselective effects of quinidine and quinine on the hERG channel, and this is the first study to explore their reversal potency on drug-induced hERG deficiency.

  18. Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells.

    Science.gov (United States)

    Dandekar, Devendra S; Lopez, Monica; Carey, Robert I; Lokeshwar, Bal L

    2005-06-20

    Many tumors constitutively express high levels of the inducible form of proinflammatory enzyme, cyclooxygenase-2 (COX-2). Increased COX-2 expression is associated with tumor cell resistance to many cytotoxic chemotherapy drugs. Furthermore, increased resistance to cytotoxic antitumor drugs is also known to be dependent on associated stromal cells in many tumors. We investigated whether prostate tumor-associated stromal cells, marrow-derived osteoblasts, affect cytotoxicity of 2 antitumor drugs, COL-3 and docetaxel (TXTR), and whether it is dependent on COX-2 activity. We further examined whether inhibiting the activity of COX-2 negate the stroma-induced decrease in drug sensitivity in tumor cells. COX-2-specific inhibitor celecoxib (CXB) was used to inhibit COX-2 activity and associated alteration in cell death signaling was investigated. Coculturing PC-3ML cells with osteoblasts decreased the cytotoxicity of the tested antitumor drugs and was associated with increased COX-2 activity in PC-3ML cells. A significant decrease in drug-induced PGE(2) increase and an increase in cytotoxicity were observed when cells were treated with COL-3 or TXTR combined with CXB. Cytotoxicity of single or combination treatment increased apoptosis, which was associated with caspase-3 and -9 activation, PARP cleavage, increased BAD protein, but decreased protein levels of XIAP and BCL-(xL). Oral administration of CXB (40 mg/kg) to mice with PC-3ML tumors for 42 days increased tumor latency, decreased tumor growth and enhanced tumor control with COL-3 or TXTR. Overall, a synergistic enhancement of antitumor activity in combination treatment was observed in vitro and an additive effect in vivo. These observations suggest a potential clinical use of combined dosing of COX-2 inhibitors and cytotoxic drugs at lower, nontoxic dose than currently used to treat advanced prostate cancer.

  19. Usefulness of in vitro combination assays of mitochondrial dysfunction and apoptosis for the estimation of potential risk of idiosyncratic drug induced liver injury.

    Science.gov (United States)

    Goda, Keisuke; Takahashi, Tadakazu; Kobayashi, Akio; Shoda, Toshiyuki; Kuno, Hideyuki; Sugai, Shoichiro

    2016-01-01

    Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown. Recently, many in vitro assays which indicate a possibility of the prediction of the idiosyncratic DILI have been reported. Among these, some in vitro assays focus on the effects of compounds on mitochondrial function and the apoptotic effects of compounds on human hepatocytes. In this study, we measured oxygen consumption rate (OCR) and caspase-3/7 activity as an endpoint of mitochondrial dysfunction and apoptosis, respectively, with human hepatocytes after treatment with compounds causing idiosyncratic DILI (troglitazone, leflunomide, ranitidine and diclofenac). Troglitazone and leflunomide decreased the OCR but did not affect caspase-3/7 activity. Ranitidine increased caspase-3/7 activity but did not affect the OCR. Diclofenac decreased the OCR and increased caspase-3/7 activity. Acetaminophen and ethanol, which are also hepatotoxicants but do not induce idiosyncratic DILI, did not affect the OCR or caspase-3/7 activity. These results indicate that a combination assay of mitochondrial dysfunction and apoptosis is useful for the estimation of potential risk of compounds to induce idiosyncratic DILI.

  20. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  1. 柳氮磺吡啶致药物超敏反应综合征%Drug-induced hypersensitivity syndrome induced by sulfasalazine:a case report

    Institute of Scientific and Technical Information of China (English)

    李兴天; 刘莉萍; 李遇梅

    2014-01-01

    A case of sulfasalazine-induced hypersensitivity syndrome was reported. A 34-year-old male, presented macu-lopapular rash with fever, alterations of white cell populations and dysfunction of the liver after one-month treatment with sul-fasalazine for ulcerative colitis. Dermatological examination showed scarlet and partly confluent maculopapules over the entire body. The rash blanches on pressure. According to the history of treatment with sulfasalazine, clinical manifestation and labo-ratory examination, drug-induced hypersensitivity syndrome was diagnosed. The treatment produced a marked improvement af-ter the initiation of systemic corticosteroids, immunoglobulin and supportive therapy.%报告1例柳氮磺吡啶致药物超敏反应综合征。患者男,34岁。因溃疡性结肠炎使用柳氮磺吡啶1个月后出现皮疹,伴发热、白细胞及肝功能异常。皮肤科检查:全身可见泛发鲜红色斑丘疹,部分融合成片,触压皮肤可褪色。结合用药史、临床表现及实验室检查诊断为药物超敏反应综合征,给予系统应用糖皮质激素、静脉注射用人免疫球蛋白、保肝及护胃等治疗后病情好转。

  2. Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort

    Science.gov (United States)

    Ulzurrun, Eugenia; Stephens, Camilla; Ruiz-Cabello, Francisco; Robles-Diaz, Mercedes; Saenz-López, Pablo; Hallal, Hacibe; Soriano, German; Roman, Eva; Fernandez, M. Carmen; Lucena, M. Isabel; Andrade, Raúl J.

    2014-01-01

    Background and Aims Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. Methods A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. Results None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. Conclusions Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility. PMID:24732756

  3. Persistence of autoreactive T cell drive is required to elicit anti-chromatin antibodies in a murine model of drug-induced lupus.

    Science.gov (United States)

    Kretz-Rommel, A; Rubin, R L

    1999-01-15

    Long-term treatment with procainamide and numerous other medications is occasionally associated with the development of drug-induced lupus. We recently established a murine model for this syndrome by disrupting central T cell tolerance. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, into (C57BL/6 x DBA/2)F1 mice resulted in the appearance of chromatin-reactive T cells and anti-chromatin autoantibodies. The current study explores in this model the role of autoreactive T cells in autoantibody production and examines why autoantibodies after a single intrathymic drug injection were much more limited in isotype and specificity. Injection of as few as 5000 chromatin-reactive T cells into naive, syngeneic mice induced a rapid IgM anti-denatured DNA response, while injection of at least 100-fold greater number of activated T cells was required for induction of IgG anti-chromatin Abs, suggesting that small numbers of autoreactive T cells can be homeostatically controlled. Mice subjected to a single intrathymic PAHA injection after receiving splenic B cells from an intrathymic PAHA-injected syngeneic donor also developed anti-chromatin Abs, but adoptive transfer of similarly primed T cells or of B cells without intrathymic PAHA injection of the recipient failed to produce an anti-chromatin response. However, anti-chromatin Abs developed after a single intrathymic PAHA injection in Fas-deficient C57BL/6-lpr/lpr mice, suggesting that activation-induced cell death limited autoimmunity in normal mice. Taken together, these results imply that chromatin-reactive T cells produced by intrathymic PAHA created a B cell population primed to somatically mutate and Ig class switch when subjected to a heavy load or second wave of autoreactive T cells.

  4. Avaliação da sonolência em estudantes universitários de turnos distintos Evaluación de la somnolencia en estudiantes universitarios de turnos distintos Evaluation of sleepiness in college students from different shifts

    Directory of Open Access Journals (Sweden)

    Danilo de Freitas Araújo

    2012-08-01

    Full Text Available Estudantes de graduação possuem altas chances de apresentar Sonolência Diurna Excessiva, devido aos horários escolares e às demandas acadêmicas. Por isso, pretendeu-se analisar níveis de sonolência de estudantes de turnos distintos. O universo foi constituído por 109 graduandos do turno matutino e 125 do noturno. Utilizou-se a Escala de Sonolência de Epworth. A amostra apresentou média total de 9,38 (DP=4,03, sendo 9,03 (DP=4,01 para o turno matutino e 9,7 (DP=3,93 para o noturno. Foram detectadas diferenças significativas nos níveis de sonolência entre turnos (η² =0,10;p Estudiantes de graduación poseen altas posibilidades de presentar Somnolencia Diurna Excesiva, debido a los horarios escolares y a las demandas académicas. Por eso, se pretendió analizar niveles de somnolencia de estudiantes de turnos distintos. El universo fue constituido por 109 graduandos del turno matutino y 125 del nocturno. Se utilizó la Escala de Somnolencia de Epworth. La muestra presentó promedio total de 9,38 (DP=4,03, siendo 9,03 (DP=4,01 para el turno matutino y 9,7 (DP=3,93 para el nocturno. Fueron detectadas diferencias significativas en los niveles de somnolencia entre turnos (η²=0,10; pUndergraduate students are a population with high chances of developing Excessive Daytime Sleepiness, due to school schedules and academic demands. Our aim was to examine the levels of sleepiness of students belonging to morning and night classes. The universe has consisted of 109 undergraduate students of the morning shift and 125 of the night shift. We have used the Epworth Sleepiness Scale. The sample had an average of 9.38 (SD=4.03, and 9.03 (SD=4.01 for the morning shift and 9.7 (SD=3.93 for the night shift. Statistical analysis showed significant differences in sleepiness between shifts (η²=0,10; p<0,00, and among male subjects and female in the two shifts (η²=0,45; p<0,00. It should therefore be considered the role of academic demands, since they

  5. 血小板活化因子在药源性严重过敏反应中的研究现状%Advance of platelet activating factor in drug-induced anaphylaxis

    Institute of Scientific and Technical Information of China (English)

    马翔; 李潇潇; 刘维; 翟所迪

    2015-01-01

    药源性严重过敏反应有难以预测、发作突然和致命性等特点,从而成为困扰临床药物使用的重要安全性因素。由于目前尚无严格的随机对照试验支持抢救药物的推荐,医生常根据临床经验用肾上腺素、抗组胺药和/或糖皮质激素应对突发的药源性严重过敏反应。血小板活化因子( PAF)信号通路可为研究药源性严重过敏反应提供崭新的视角。本文将就药源性严重过敏反应的临床和流行病学特点、PAF通路、抗PAF通路的药物等进行概述。%The acute unpredictably life -threatening characteristic of drug-induced anaphylaxis hinders the safe use of clinical medication.In the absence of rigid randomized controlled trials supporting the recommen-dations for the treatment of immediate onset, doctors often treat drug-induced anaphylaxis with epinephrine, antihistamines and/or glucocorticoids.The researches in platelet activating factor signaling path-way could provide a novel perspective for drug-induced anaphylaxis.This review will briefly introduce the clinical and epidemiological characteristics of drug-induced anaphylaxis, platelet activating factor pathway and drugs targeting at this pathway.

  6. 药源性高血压的发病机制、致病药物及其防治%Drug-induced hypertension: mechanism, causative durgs, prevention, and management

    Institute of Scientific and Technical Information of China (English)

    刘琛; 王育琴

    2012-01-01

    Drug-induced hypertension is one of the common adverse drug reactions. The mechanism of drug-induced hypertension may involve stimulation of sympathetic nervous system activity, sodium and water retention, renin-angiotensin-aldosterone system activation, and changes in function and structure of arterial elasticity. Clinical presentations are increased blood pressure, rebound phenomenon, and even hypertensive crisis. The risk factors for drug-induced hypertension are advanced age, sex, genetic causes, previous history of hypertension, overweight, susceptibity to sodium, and underlying diseases. The drugs known to cause hypertension should be avoided in high-risk patients; if drug treatment is necessary, the treatment should start with a minimum dosage and blood pressure should be monitored during treatment. Once drug-induced hypertension occurs, the drug should be discontinued immediately or the dosage should be reduced, and symptomatic treatment should be given.%药源性高血压为常见药物不良反应之一,其发病机制包括交感神经活动亢进,肾性水钠潴留,肾素-血管紧张素-醛固酮系统激活,以及动脉弹性功能和结构改变.临床表现为血压升高、反跳现象,甚至出现高血压危象.高危因素包括高龄、性别、遗传原因、既往高血压病史、超重、钠敏感、基础疾病.高危人群应避免使用可致血压升高的药物;必须使用时,应从最小剂量开始并应监测血压水平.一旦出现高血压应立即停药或减少剂量,并予对症治疗.

  7. STOP-Bang questionnaire is superior to Epworth sleepiness scales,Berlin questionnaire, and STOP questionnaire in screening obstructive sleep apnea hypopnea syndrome patients

    Institute of Scientific and Technical Information of China (English)

    Luo Jinmei; Huang Rong; Zhong Xu; Xiao Yi; Zhou Jiong

    2014-01-01

    Background Obstructive sleep apnea hypopnea syndrome (OSAHS) is underdiagnosed.Screening patients at high risk of OSAHS is extremely important.Using the standard questionnaire to screen OSAHS is a practical method.This study aimed to evaluate the value of the STOP-Bang questionnaire (SBQ) in screening OSAHS in sleep-disordered breathing clinic by comparing it with the Epworth sleepiness scales (ESS),Berlin questionnaire,and STOP questionnaire.Methods In this study,212 patients at the sleep-disordered breathing clinic of the Peking Union Medical College Hospital between May 2011 and January 2012 were prospectively included.They were asked to fill in the SBQ,ESS,Berlin questionnaire,and STOP questionnaire before overnight polysomnography (PSG).Using PSG as gold standard,the sensitivities and specificities of SBQ were compared with those of ESS,Berlin questionnaire,and STOP questionnaire.Results There was no significance in applying ESS score ≥11 to screen OSAHS and detect moderate and severe OSAHS (P >0.05).SBQ was superior to Berlin questionnaire and STOP questionnaire in screening OSAHS and detecting the severity of OSAHS patients.The sensitivities of SBQ score ≥3 with apnea hypopnea index (AHI) ≥5/h,AHI ≥15/h,and AHI ≥30/h as gold standards were 94.9%,96.5%,and 97.7%,respectively.The specificities were 50.0%,28.6%,and 17.9%,respectively.The area upper curves were 0.815 (0.706-0.925,P <0.01),0.746 (0.665-0.828,P <0.01),and 0.751 (0.686-0.817,P <0.01),respectively.According to SBQ,the population was classified into high-risk group and low-risk group.The gender,BMI,neck circumference,AHI,LSpO2,and number of subjects ofAHI ≥5/h,AHI ≥15/h,and AHI ≥30/h of these two groups were significantly different.Conclusions The SBQ has superior predictive value compared with ESS,Berlin questionnaire,and STOP questionnaire.It should be used further in screening for OSAHS in the general population.

  8. A Water Extract of Mucuna pruriens Provides Long-Term Amelioration of Parkinsonism with Reduced Risk for Dyskinesias

    OpenAIRE

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

    2010-01-01

    Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of Mucuna pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decar...

  9. 药物性肝损伤200例临床分析%Retrospective analysis of 200 patients with drug induced liver injury

    Institute of Scientific and Technical Information of China (English)

    张长平; 崔向丽; 王咏梅

    2014-01-01

    目的:探讨药物性肝损伤患者的临床特点及发病因素。方法回顾性分析药物性肝损伤患者服药史、临床表现、基础疾病、治疗及转归等。结果200例患者中女139例,男61例,涉及药品169种,其中前3位是中药(48.5%)、抗感染药(11.2%)、抗肿瘤药(8.2%)。患者基础疾病主要为心血管病(14.5%)、感染性疾病(10.3%)、皮肤病(8.8%)、骨关节病(8.4%)、肿瘤(7.9%)等。200例患者治愈146例,好转53例,死亡1例。结论引起肝损伤的药物以中药为主,临床表现形式多样,但转归较好。%Objective To investigate the characteristics and risk etiological factors of drug-induced liver injury(DILI) cases,and provide information for clinical prevention and treatment.Methods The clinical data of 200 patients (including 139 female and 71 male ) with DILI was retrospectively analyzed according to their history of medicine, clinical manifestations,underlying diseases,treatment and prognosis.Results These 200 cases involved 169 etiological drugs,of which the top 3 were traditional Chinese medicine,anti-infective drugs and anti-tumor drugs.The primary underlying diseases of these patients were cardiovascular disease,infectious diseases,skin diseases,osteoarthrosis,tumors and so on. Of those 200 patients,146 were cured,53 improved and 1 died.Conclusion DILI is dominated by traditional Chinese medicine,with various clinical manifestations and favorable prognosis.

  10. Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI in China.

    Directory of Open Access Journals (Sweden)

    Penghui Shang

    Full Text Available BACKGROUND: Anti-tuberculosis drug induced liver injury (ATLI is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB treatment in China. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%. Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02% ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25% recovered, 18 (16.98% improved, 2 (1.89% failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89% died as result of ATLI. Of all the ATLI cases, 74 (69.81% cases changed their anti-TB treatment, including 4 (3.77% cases with medication administration change, 21 (19.81% cases with drugs replacement, 54 (50.94% cases with therapy interruption, and 12 (11.32% cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46% cases had TB cured in time, 48 (46.60% cases had therapy prolonged, and 2 (1.94% cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05 risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI, 1.23-3.60 risk of prolonged intensive treatment phase. CONCLUSIONS/SIGNIFICANCE: ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the

  11. 药物性肝病248例临床分析%Clinical analysis of 248 cases of drug induced liver diseases

    Institute of Scientific and Technical Information of China (English)

    杨立新

    2012-01-01

    Objective To explore the etiology, clinical features and prognosis of drug-induced liver disease (DILD). Methods A retrospective analysis was taken of DILD in hospitalized for medication history, clinical manifestations. Results The causes of DILD were mainly antibiotics (12. 1% ), medicine (23.0% ), anti-TB drugs (8.0% ), anti-cancer drugs (7. 2%), immunosuppressive agents (14..5%). The clinical manifestations were mainly anorexia (62.5%), fatigue (55. 1%), nausea (51.3%), jaundice (37.2%), abdominal pain (18.3%), pruritus (12.9% ), rash (4.6% ). Conclusion Clinicians should pay attention to and strengthen the DILD prevention, diagnosis and treatment.%目的 分析药物性肝病( DILD)的病因、临床特点及预后,提高临床医生对DILD的诊疗水平.方法 采用回顾性分析的方法对248例DILD住院患者的用药史、临床表现以及预后等进行研究.结果 引起DILD的药物以抗生素类药物(12.1%)、中药(23.0%)、抗结核药物(8.0%)、抗肿瘤药物(7.2%)、免疫抑制剂(14.5%)为常见.临床表现以纳差(62.5%)、乏力(55.1%)、恶心(51.3%)、黄疸(37.2%)、腹痛(18.3%)、瘙痒(12.9%)、皮疹(4.6%)等多见;肝性脑病、腹水、凝血酶原时间、黄疸等因素与患者死亡相关.结论 临床医生应重视和加强DILD的预防、诊断和治疗.

  12. Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

    Directory of Open Access Journals (Sweden)

    Joonhee Cho

    Full Text Available BACKGROUND AND AIMS: Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI. METHODS: To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function. RESULTS: BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6. CONCLUSIONS: 17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a

  13. 茵栀黄颗粒致药物性肝炎2例%Two cases of drug-induced hepatitis caused by Yinzhihuang granules

    Institute of Scientific and Technical Information of China (English)

    蒋杰; 劳国琴; 张谊芳

    2014-01-01

    Case 1:one 46-year-old male patient developed vomiting, lack of power, yellow urine with chill and fever after receiving Yinzhihuang granules for the treatment of abnormal liver function. The highest body temperature was 39.0℃. All the above symptoms alleviated after discontinuation of the drug. Two months later, Yinzhihuang granules were taken again and the symptoms of chill, fever, lack of power and yellow urine reappeared. Laboratory examinations were as follows:TBIL 65.7 µmol·L-1, DBIL 34.8 µmol·L-1, ALT 939.2 IU·L-1, AST 489.9 IU·L-1,γ-GT 785.0 IU·L-1. Drug-induced hepatitis was diagnosed and Yinzhihuang granules were stopped. Treatments of protecting liver function, depressing transaminase and abating jaundice were given to the patient. After 45 days, the patient discharged with normal liver function. Case 2:one 51-year-old female patient was admitted to hospital because of acute hepatitis E. The liver function of the patient recovered after 2-month treatment, and then the patient discharged with Yinzhihuang granules. Ten days later, the patient developed fever, vomiting, abdominal distention and anorexia. Laboratory ifndings were:TBIL 22.8 µmol·L-1, DBIL 16.0 µmol·L-1, ALT 308.0 IU·L-1, AST 309.0 IU·L-1,γ-GT 237.0 IU·L-1, AKP 258.0 IU·L-1. The patient was hospitalized again and the clinical diagnosis was drug-induced hepatitis. Yinzhihuang granules were stopped, and the symptomatic treatments of protecting liver function, depressing transaminase and abating jaundice were given immediately. About 35 days later, hepatic function of the patient recovered to normal.%病例1:患者,男性,46岁,因肝功能异常服用茵栀黄颗粒降酶退黄治疗,后出现呕吐、乏力,小便颜色进行性加深,并伴有畏寒、发热,体温最高达39.0℃。自行停药后体温降至正常,症状缓解。2个月后再次服用茵栀黄颗粒,畏寒、发热、乏力、尿黄症状再次出现。于外院查肝功能示:TBIL 65

  14. 53例药源性间质性肺炎的文献分析%Literature Analysis of 53 Reports of Drug-induced Interstitial Pneumonia

    Institute of Scientific and Technical Information of China (English)

    胡美绘; 孙安修

    2014-01-01

    目的:探讨引起间质性肺炎的药品种类及其临床表现特点。方法检索中国医院数字图书馆、中国知网、万方数据库中1994~2013年,关键词为“间质性肺炎”的相关文献,进行归纳总结。结果共检索出相关文献74篇,报道53例药源性间质性肺炎,涉及15种药物,包括吉非替尼(15例)、利妥西单抗(9例)、来氟米特(8例)、胺碘酮(8例)、厄洛替尼(5例)、干扰素(2例)、5-氟尿嘧啶(1例)、粒细胞集落刺激因子(1例)、吉西他滨(1例)、卡莫司汀(1例)、麻疹疫苗(1例)、百草枯(1例)等。53例患者中,2例治疗结果不详;治愈17例(33.33%),好转19例(37.26%),死亡15例(29.41%)。结论各药品引起间质性肺炎发病机制尚不明确,临床表现相似。发病率较高的药物有吉非替尼、利妥西单抗、来氟米特、胺碘酮、厄洛替尼。%Objective To study the drugs leading to interstitial pneumonia and analyze their clinical characteristics. Methods We searched the literatures from 1994 to 2013 by key words of "interstitial pneumonia" in China Digital Library, China National Knowledge Infrastructure, Wanfang Database, and summarized them. Results A total of 74 relevant articles were identified, which reported 53 cases of drug-induced interstitial neumonia, involving 15 kinds of drugs. The drugs included gefitinib(15), rituximab(9), leflunomide(8), amiodarone(8), erlotinib(5), interferon(2), 5-fluorouracil(1), granulocyte colony-stimulating factor(1), gemcitabine(1), carmustine (1), measles vaccine (1), paraquat(1), et al.The result showed that 53 cases contained 17 cases(33.33%) cured, 19 cases(37.26%) improved , 15 cases(29.41%) died and 2 cases unclear. Conclusion The clinical manifestations of interstitial pneumonia induced by drugs were similar, but the pathogenesis was unknown. The drugs leading to higher incidence were gefitinib, rituximab

  15. Targeting Mcl-1 for multiple myeloma (MM) therapy: drug-induced generation of Mcl-1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation.

    Science.gov (United States)

    Fan, Fengjuan; Tonon, Giovanni; Bashari, Muhammad Hasan; Vallet, Sonia; Antonini, Elena; Goldschmidt, Hartmut; Schulze-Bergkamen, Henning; Opferman, Joseph T; Sattler, Martin; Anderson, Kenneth C; Jäger, Dirk; Podar, Klaus

    2014-02-28

    Myeloid cell leukemia-1 (Mcl-1, HGNC: 6943), a pro-survival member of the Bcl-2 family, plays a crucial role in Multiple Myeloma (MM) pathogenesis and drug resistance, thus representing a promising therapeutic target in MM. A novel strategy to inhibit Mcl-1 activity is the induction of ubiquitin-independent Mcl-1 degradation. Our own and other previous studies have demonstrated caspase-dependent generation of a 28kDa Mcl-1 fragment, Mcl-1(128-350), which inhibits MM cell proliferation and survival. Here, we show that similar to bortezomib, the novel proteasome inhibitors carfilzomib and ixazomib, as well as staurosporine and adaphostin, induce the generation of Mcl-1(128-350) in MM cells. Next, the molecular sequelae downstream of Mcl-1(128-350), which mediate its pro-apoptotic activity, were delineated. Surprisingly, we observed nuclear accumulation of drug-induced or exogenously overexpressed Mcl-1(128-350), followed by elevated mRNA and protein levels of c-Jun, as well as enhanced AP-1 reporter activity. Moreover, drug-induced AP-1 activity was blocked after introducing a point mutation into the highly conserved Mcl-1 caspase-cleavage site Asp127, but not Asp157. Consequently, drug-triggered cell death was significantly decreased in MM cells transfected with Mcl-1 D127A, but not with Mcl-1 D157A. Consistent with these data, treatment with bortezomib triggered c-Jun upregulation followed by apoptosis in Mcl-1(wt/wt), but not Mcl-1(Δ/null) murine embryonic fibroblasts (MEFs). Transfection of a plasmid carrying Mcl-1(wt) into Mcl-1(Δ/null) MEFs restored bortezomib-induced Mcl-1 fragmentation, c-Jun upregulation and AP-1 reporter activity. Finally, our data indicate that drug-induced generation of a pro-apoptotic Mcl-1 fragment followed by c-Jun upregulation may also be a novel therapeutic approach in other tumor entities.

  16. Comparative observation of primiparae undergone drug-induced abortion or artificial abortion on subsequent pregnancy%初产妇药物流产与人工流产术后对再妊娠影响的对比观察

    Institute of Scientific and Technical Information of China (English)

    丘东海; 叶娉婷

    2013-01-01

    目的:比较初产妇药物流产后和人工流产术后对再妊娠的影响,为选择合适、安全的流产方式提供临床参考.方法:采用回顾性调查方法对135例有人工流产术史、126例有药物流产史及130例无流产史的初产妇进行比较,观察其妊娠期和分娩期并发症的发生情况以及妊娠结局.结果:妊娠期人流组先兆流产发生率明显高于药流组和无流产组,差异有统计学意义(χ2=14.993,P0.05).分娩期人流组产后出血、胎盘粘连和胎盘残留的发生率明显高于药流组和无流产组,χ2分别为22.146、12.211、9.387,P值均0.05).结论:初产妇药物流产后对再次妊娠影响小于人工流产术后,可考虑作为临床终止早孕的首先选择.%Objective :To observe the efforts of drug-induced aboition or aitifirial aboition for primiparous women on their subsequent pregnancies for cliniral evidence to determine a safe and adequate means for termination of pregnancy. Methods: Retrospective comparative study was performed in 135 primiparae undergone artificial aboition, 126 with drug-induced aboition history and 130 primiparity without aboition to examine outcomes of subsequent pregnancy and complications associated with gestation and delivery. Results : Higher incidence of threatened aboition during the gestation period was found in women undergone artificial aboition as compared with those with drug-induced aboition or without aboition history. The difference was significant ( x2 = 14. 993 , P 0. 05 ). Similarly, Mothers with a history of artificial aboition had significantly higher incidence of postpaitum hemorrhage, placenta! adherence and residual placenta in labor than those experienced drug-induced aboition or no aboition ( x2 - 22. 146, x2 -12.211, x2 - 9. 387 , respectively ,P 0. 05 ). Conclusion-. Ding-induced aboition for prhnigravidas seem to produce less effects on their subsequent pregnancies than artificial intervention, and may be recommended as

  17. Cansancio y somnolencia en conductores de ómnibus interprovinciales: estudio comparativo entre formalidad e informalidad Fatigue and sleepiness in interprovincial road bus drivers: comparative study between formality and informality

    Directory of Open Access Journals (Sweden)

    Gustavo R. Liendo

    2010-06-01

    Full Text Available Objetivos. Comparar los niveles de cansancio, somnolencia y sus repercusiones entre conductores formales e informales de ómnibus interprovinciales. Evaluar las condiciones laborales en ambos grupos de estudio. Materiales y métodos. Se realizó un estudio transversal comparativo con muestreo no probabilístico. Se incluyó 100 empresas de transporte terrestre, de las cuales 17 fueron formales según registros oficiales del Ministerio de Transportes y Comunicaciones (MTC, asimismo, los conductores se catalogaron como formales o informales. La encuesta incluía un cuestionario y la versión peruana validada de la escala de somnolencia de Epworth. Resultados. Participaron 71 conductores formales y 274 informales, todos fueron varones. De 134 conductores que pertenecían a las empresas formales de acuerdo al MTC, sólo 43 (32% pertenecen al grupo formal en base a los criterios propuestos. El 48% (34 de los conductores formales y el 43% (118 de los informales duermen menos de siete horas al día. Admitieron haberse accidentado o "casi accidentado" el 48% (34 de los formales y 135 (49% informales; el horario más frecuente fue entre la 01.00 y 04.00 horas. La madrugada es el período en que ambos grupos sienten más cansancio. El 44% (30 de los conductores formales y el 54% (144 de informales realizan cinco o más turnos nocturnos por semana. Del total de los entrevistados, el 16% (56 presentaron somnolencia. La asociación con accidentes de tránsito fue similar. Conclusiones. Los niveles de cansancio y somnolencia fueron similares entre conductores formales e informales. Aquellas empresas catalogadas como formales, presentan alto porcentaje de informalidad entre sus conductores.Objectives. To compare the levels of fatigue, sleepiness and their consequences between formal and informal drivers of interprovincial buses. To evaluate labor conditions between both study groups. Materials and methods. A comparative cross-sectional study was performed with

  18. miR-140-5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells

    Science.gov (United States)

    Wei, Renxiong; Cao, Gang; Deng, Zhouming; Su, Jiajia; Cai, Lin

    2016-01-01

    Acquisition of drug-resistant phenotypes is often associated with chemotherapy in osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-140 (miR-140-5p, miRBase ID: MIMAT0000431) expression induced by chemotherapeutic drugs in osteosarcoma cells. Then we determined the promotory role of miR-140-5p to the chemotherapy-induced autophagy. Our results demonstrated that miR-140-5p expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by up-regulated autophagy. The increased miR-140-5p expression levels up-regulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Importantly, miR-140-5p regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (IP3k2). Therefore, the results of the present study demonstrated that miR-140-5p mediated drug-resistance in osteosarcoma cells by inducing autophagy. The present study provides evidence of miRNA regulation of autophagy through modulation of IP3 signalling. The present study recognized a novel mechanism of chemoresistance in osteosarcoma cancers. PMID:27582507

  19. Surgical management of venous drug-induced infective endocarditis%静脉注射吸毒者感染性心内膜炎的外科治疗

    Institute of Scientific and Technical Information of China (English)

    杜巍; 辛军; 王厚强; 周伟; 李伟阳

    2009-01-01

    Objective To summarize the experience of surgical treatment of venous drug-induced infective endocarditis(IE). Methods The 17 cases of drug-induced IE were found to have valvular vegetations,16 patients had involvement of tricuspid valve, 1 mitral valve associated with ventrieular septal defect. Preoperative blood culture was positive in 8 patients. The operations included tricuspid valve repair (6 cases),tricuspid valve replacement(8 cases), mitral valve replacement and VSD closure(1 cases). Results All patients were alive and discharges. After follow-up of 6 months to 6 years, 1 case had severd tricuspid alve regurgitation, 1 had haemoptysis because of incorrect anticoagulation. Conclusions This study indicated surgical intervention is effective treatment of venous drug-induced infective endocarditis.%目的 探讨静脉注射毒品所致感染性心内膜炎的外科治疗经验.方法 17例患者静脉注射毒品史2~10年,均有心脏瓣膜赘生物;其中三尖瓣赘生物并关闭不全16例,二尖瓣赘生物并关闭不全合并室间隔缺损1例,术前血培养阳性8例.三尖瓣置换术8例,三尖瓣成形术8例,二尖瓣置换同期室间隔缺损修补术1例.术后平均随访(44.7 ±19.1)月.结果 全部患者治愈出院,心功能明显改善,随访期间抗凝不当致大咯血1例,三尖瓣重度返流1例.结论 外科手术修复受累瓣膜或置换瓣膜是治疗静脉吸毒性感染性心内膜炎的有效手段.

  20. Comparativo da classificação de Fujita no paciente acordado e sob sonoendoscopia A comparison of the Fujita classification of awake and drug-induced sleep endoscopy patients

    Directory of Open Access Journals (Sweden)

    Fabio Augusto Winckler Rabelo

    2013-02-01

    Full Text Available São poucos os estudos que comparam resultados endoscópicos no paciente acordado com o mesmo paciente sob sono induzido por drogas. OBJETIVOS: O objetivo do presente estudo é comparar os acha dos endoscópicos num mesmo paciente, em dois momentos diferentes: ambulatorial e sob sedação com propofol, por meio da classificação de Fujita. Desenho do estudo: estudo de coorte transversal. MÉTODO: Trinta e quatro pacientes foram submetido ao exame otorrinolaringológico ambulatorial, incluindo nasoendoscopia com manobra de Müller com o paciente acordado e à sonoendoscopia com propofol. A classificação de Fujita foi adotada para comparar os dois exames endoscópicos. Correlacionamos a concordância entre os exames com dados clínicos dos pacientes, como Índice de Massa Corporal, idade e gravidade da síndrome da apneia obstrutiva do sono. RESULTADOS: Não houve concordância nenhuma entre os dois exames endoscópicos, seja para o grupo no geral, seja para cada um dos subgrupos analisados. CONCLUSÃO: Não existe concordância entre os achados endoscópicos com o paciente acordado e os mesmos com o paciente com sono induzido.Only a few studies have compared the outcomes of patients kept awake during endoscopic examination and subjects submitted to drug-induced sleep endoscopy. OBJECTIVE: This study aimed to compare the endoscopic findings of patients submitted to outpatient endoscopy and endoscopic examination with sedation by propofol based on the Fujita Classification. METHOD: This cross-sectional cohort study enrolled 34 patients. The subjects underwent ENT examination, nasal endoscopy with Müller's maneuver, and drug-induced sleep endoscopy with propofol. The Fujita Classification was used to compare the two modes of endoscopic examination. The examinations were correlated to patient clinical data such as BMI, age, and OSAS severity. RESULTS: There was no agreement between the two modes of endoscopic examination, whether for the group in

  1. 牙周基础治疗对药物性牙龈增生的疗效观察%To Observe the Effect of Initial Periodontal Therapy on Drug-induced Gingival Hyperplasia

    Institute of Scientific and Technical Information of China (English)

    金晓丽

    2015-01-01

    目的:研究探讨牙周基础治疗对药物性牙龈增生的治疗效果。方法随机抽取我院2011年4月-2013年4月收治的因药物治疗引起牙龈增生患者300例为研究对象。给予所有的研究对象牙周基础治疗,观察其临床效果。结果在患者治疗一段时间后显示,患者的牙龈增生指数、牙周探诊深度、菌斑指数以及出血指数具有显著的变化,随着患者治疗时间的持续以及后续口腔卫生的维持,其治疗效果显著优于牙周基础治疗之前,数据符合统计学差异(P<0.05)。结论针对药物性牙龈增生的患者,基于牙周基础治疗能够改善患者临床症状,为药物性牙龈增生提供新的治疗方案,值得在临床上推广使用。%Objective To study the effects of periodontal therapy on drug-induced gingival hyperplasia therapeutic effect.Methods Randomly selected in our hospital in 2011 April~2013 year in April were caused due to drug treatment in patients with gingival hyperplasia 300 cases as the research object. Given al of the research on ivory periodontal treatment, and to observe its clinical effect. Results The display in the treatment for a period of time after the index, gingival hyperplasia patients, patients with periodontal probing depth, plaque index and bleeding index has significant changes, with the duration of folow-up treatment of patients, oral hygiene maintenance, before its therapeutic effect is significantly better than that of periodontal basic treatment, data in accordance with statistical difference (P<0.05).Conclusion For patients with drug-induced gingival hyperplasia, periodontal therapy can improve the clinical symptoms of patients based on, provide new treatment for drug-induced gingival hyperplasia, worthy of promotion in clinical use.

  2. Retrospective analysis of 45 cases of pediatric drug-induced liver injury%小儿药物性肝损伤45例回顾性分析

    Institute of Scientific and Technical Information of China (English)

    王英英

    2015-01-01

    Objective To investigate the clinical features of pediatric liver damage and the medication,to pro-vide the basis for specification of pediatric medication,reduce the incidence of drug-induced liver injury. Methods Clinical data of 45 cases of drug-induced liver injury in pediatrics department from January 2013 to June 2014 were ret-rospectively analyzed and compared. Results There was no significant difference in sex proportion,average duration,type of injury between the children who were less than 6 years old and children who were more than 6 years old ( P>0. 05). Drug-induced liver injury in children first diagnosed mainly as anorexia and vomiting,the main clinical mani-festations were anorexia,listlessness,fatigue,nausea,vomiting,diarrhea,abdominal pain,and so on. ALT and AST in children with liver cell injury type were higher than that of cholestasis type,with lower ALP,PTA and TB levels,ALP,PTA and TB levels of hybrid type was in the middle among the three types. There were significant difference in the a-bove indexes among the three groups (P6岁患儿在性别、平均病程、损伤类型方面比较差异无统计学意义( P>0. 05 ). 药物性肝损伤患儿首诊主要表现为纳差和呕吐,主要临床表现为纳差、精神萎靡、乏力、恶心呕吐、腹泻和腹痛等.肝细胞损伤型患儿ALT和AST指标较胆汁淤积型高,ALP、PTA和TB指标较胆汁淤积型低,混合型数据居中,三组比较差异有统计学意义( P<0. 01 ). 抗菌药物、解热镇痛药、阿奇霉素和中药致小儿肝损伤的比例分别为33. 3%、15. 6%、13. 3%、13. 3%. 结论 小儿药物性肝损伤尚无典型特征,诊断时应综合各种临床资料、生化指标、症状体征等,应注意对高危用药的监测和合理应用.

  3. In vitro evaluation of hepatotoxic drugs in human hepatocytes from multiple donors: Identification of P450 activity as a potential risk factor for drug-induced liver injuries.

    Science.gov (United States)

    Utkarsh, Doshi; Loretz, Carol; Li, Albert P

    2016-08-01

    A possible risk factor for drug-induced hepatotoxicity is drug metabolizing enzyme activity, which is known to vary among individuals due to genetic (genetic polymorphism) and environmental factors (environmental pollutants, foods, and medications that are inhibitors or inducers of drug metabolizing enzymes). We hypothesize that hepatic cytochrome P450-dependent monooxygenase (CYP) activity is one of the key risk factors for drug induced liver injuries (DILI) in the human population, especially for drugs that are metabolically activated to cytotoxic/reactive metabolites. Human hepatocytes from 19 donors were evaluated for the activities of 8 major P450 isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Extensive individual variations were observed, consistent with what is known to be in the human population. As CYP3A4 is known to be one of the most important P450 isoforms for drug metabolism, studies were performed to evaluate the relationship between the in vitro cytotoxicity of hepatotoxic drugs and CYP3A4 activity. In a proof of concept study, hepatocytes from six donors (lots) representing the observed range of CYP3A4 activities were chosen for the evaluation of in vitro hepatotoxicity of four drugs known to be associated with acute liver failure: acetaminophen, cyclophosphamide, ketoconazole, and tamoxifen. The hepatocytes were cultured in collagen-coated plates and treated with the hepatotoxicants for approximately 24 h, followed by viability determination based on cellular adenosine triphosphate (ATP) contents. HH1023, the lot of hepatocytes with the highest CYP3A4 activity, was found to be the most sensitive to the cytotoxicity of all 4 hepatotoxic drugs, thereby suggesting that high CYP3A4 activity may be a risk factor. To further validate the relationship, a second study was performed with hepatocytes from 16 donors. In this study, the hepatocytes were quantified for CYP3A4 activity at the time of treatment. Results of the

  4. Força muscular respiratória e capacidade funcional em idosas hipertensas com sonolência diurna excessiva Respiratory muscle strength and physical fitness in hypertensive elderly women with excessive daytime sleepiness

    Directory of Open Access Journals (Sweden)

    Rafaela Pedrosa

    2010-06-01

    Full Text Available O objetivo do estudo foi verificar se a sonolência diurna excessiva (SDE afeta a capacidade funcional (CF e força muscular respiratória entre idosas hipertensas. O estudo avaliou 32 idosas hipertensas, divididas em dois grupos (com SDE, n=17, 64,9±5,3 anos; e sem SDE, n=15, 65,9±5,5 anos, quanto a: força muscular respiratória, por manovacuometria; CF, pelo Questionário para avaliação de limitação das atividades e por testes de aptidão funcional; nível de atividade física, pelo questionário internacional de atividade física IPAQ; grau de SDE, pela escala de sonolência de Epworth; qualidade do sono, pelo índice de qualidade do sono de Pittsburgh; e intensidade do ronco, pela escala de ronco de Stanford. Os dois grupos, homogêneos quanto a características antropométricas e da hipertensão, foram comparados estatisticamente quanto a parâmetros de sono, pressões respiratórias máximas, nível de atividade física e CF. Foi encontrada diferença significativa na qualidade do sono (p=0,03, tendo as hipertensas com SDE qualidade de sono muito ruim; porém não foram encontradas diferenças significativas entre os grupos nas pressões inspiratória e expiratória máximas, nem quanto aos testes de CF. Conclui-se que a força dos músculos respiratórios não sofre alteração em decorrência da presença de SDE em idosas hipertensas e que essa sonolência não interfere na capacidade funcional.The purpose of the study was to inquire whether excessive daytime sleepiness (EDS affects functional capacity (FC and respiratory muscle strength in elderly hypertensive patients. Thirty-two elderly hypertensive female patients were divided into two groups (with EDS, n=17, mean age 64.9±5.3; without EDS, n=15, mean age 65.9±5.5 and were assessed as to respiratory muscle strength by spirometry; FC, by the Questionnaire on limitations in physical activities and by functional fitness tests; physical activity level, by the International

  5. Research progress in pathogenesis,prevention and treatment of drug-induced dry eye disorders%药源性干眼症发生发展机制及防治研究进展

    Institute of Scientific and Technical Information of China (English)

    白芳; 陶海; 王朋

    2016-01-01

    药源性干眼症可致眼表潜在损伤,主要临床表现为眼部干涩、烧灼感、异物感、眼痒、眼红、畏光、视物模糊等,影响患者生活质量。引起药源性干眼症的药物包括全身使用的抗胆碱能药物如抗精神病药、抗组胺和减充血剂、激素、化疗药、抗病毒药、抗疟疾药、抗风湿药、螯合剂、神经毒素;眼周及眼局部使用的含或不含防腐剂的滴眼液及肉毒素等。药源性干眼症的发病机制与上述药物导致腺体分泌减少、影响水液层和黏蛋白层分泌、干扰泪膜脂质层使脂质分泌量减少、泪膜不稳定,诱发炎性反应损伤结膜杯状细胞、眼睑腺体、结膜及角膜,以及降低角膜感觉程度、减少传入神经冲动使泪液生成减少等有关。应避免不必要的全身或局部多重用药,确诊药源性干眼症后应停用有关药物或换用致干眼症不良反应程度较低的药物。%Drug-induced dry eye disorders may cause potential damage to the ocular surface which can seriously decrease the quality of life of patients. The main clinical manifestations include eye dryness, burning-like feeling,foreign body sensation,itching,redness,photophobia,and blurred vision. The common drugs causing drug-induced dry eye disorders include systemic anticholinergic drugs such as psychotropic drugs,antihistamines and decongestant,steroids,chemotherapeutic drugs,antiviral drug,anti-malarial,antirheumatic agents,chelating agent,and neurotoxin. The drug for local application around the eye include eye drops and botox with or without preservative. The main mechanisms of drug-induced dry eye disorders may involve decrease of glandular secretion,affecting the aqueous layer and mucin layer;disturbing the stabilization of tear lipid layer and decreasing the lipid secretory volume;inducing the inflammatory reaction which damages the conjunctival goblet cells,eyelid glands,conjunctiva and cornea;reducing the

  6. Sonolência excessiva diurna na população geral de um município brasileiro Excessive daytime sleepiness in the general population of Brazilian city