RESUMO
BACKGROUND: Serum level of microRNA-122 (miR-122) has been reported as a sensitive diagnostic biomarker for detecting liver injury, comparable to the aminotransferases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are increased in other conditions, such as acute skeletal muscle injury (ASMI). We determined whether miR-122 is nonspecifically increased in patients suffering from ASMI. METHODS: We measured ALT, AST, creatine kinase (CK), and miR-122 in 3 groups: healthy controls (n = 24), patients with ASMI (total n = 29, 11 with recreational drug use and 18 without recreational drug use), and patients with acute liver injury (ALI; n = 14). RESULTS: Levels of ALT, AST, and CK increased 83%, 97%, and 100% for patients with ASMI and 100% for all 3 enzymes in ALI patients. In contrast, miR-122 increased in 34% of patients with ASMI (44.4% with recreational drug use and 18.2% without recreational drug use) and 100% of ALI patients. In 2 drug-induced liver injury cases, miR-122 increased about 12-24 hours before ALT and AST. CONCLUSION: Recreational drug misuse is associated with both rhabdomyolysis and drug-induced liver injury (DILI). The traditional liver function markers AST and ALT were nonspecifically increased in the majority of patients with ASMI. miR-122 is only increased in patients at risk for DILI and demonstrates superior specificity for liver injury.
RESUMO
BACKGROUND: Kratom (Mitragyna speciosa), an evergreen tree native to Southeast Asia, contains alkaloids that cause both stimulant and opioid-like effects. In the United States, its use continues to grow. Kratom products, however, are unregulated and nonstandardized, and reports of adulteration have been described previously. CASE REPORT: A 21-year-old African-American woman with a history of occasional headaches and self-treatment with internet-purchased kratom presented to the emergency department with the chief symptoms of nausea, vomiting, and left flank pain. Laboratory tests showed a markedly elevated serum creatinine of 4.25 mg/dL (reference range 0.6-1.2 mg/dL) and proteinuria. A computed tomography scan of the abdomen and pelvis was unrevealing. A standard urine screen for drugs of abuse was positive for opiates. A confirmatory testing revealed the presence of hydrocodone and morphine in the urine. Hydrocodone, morphine, and mitragynine were identified in a sample of kratom leaves provided by the patient. The patient's renal function improved with supportive care and normalized 1 month post discharge after kratom discontinuation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite widespread use, relatively little is known about kratom's adverse effects, particularly regarding its potential to cause renal insufficiency. This case illustrates the vital importance of recognizing that adulteration of unregulated products is certainly a possibility and clinicians may continue to see a rise in adverse effects, given kratom's increasing popularity.
Assuntos
Injúria Renal Aguda , Mitragyna , Injúria Renal Aguda/induzido quimicamente , Adulto , Assistência ao Convalescente , Analgésicos Opioides/efeitos adversos , Creatinina , Feminino , Humanos , Hidrocodona/efeitos adversos , Mitragyna/efeitos adversos , Morfina , Alta do Paciente , Estados Unidos , Adulto JovemRESUMO
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Adolescente , Adulto , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
No dia 05 de agosto de 2010, no Hotel Blue Tree, no bairro do Morumbi em São Paulo, a Sociedade Brasileira de Hepatologia realizou uma reunião de expertos para discutir alguns assuntos importantes referentes à toxicidade hepática. Esta reunião foi de responsabilidade exclusiva da Sociedade Brasileira de Hepatologia (SBH), sem interferência de agências ou da indústria farmacêutica. Dentre os assuntos discutidos, três deles mereceram destaque pelo volume de solicitações de esclarecimentos encaminhadas diretamente à Sociedade Brasileira de Hepatologia. O site da SBH recebe com frequência tais solicitações de outras sociedades ou diretamente de colegas, assim como do público não-médico, por questões pertinentes a estes assuntos: 1. papel do acetaminofen/paracetamol nas alterações hepáticas da dengue; 2. eficácia e segurança da medicina alternativa (homeopatia, medicina natural, fitoterápicos); 3. alterações hepáticas induzidas por analgésicos, antitérmicos e anti-inflamatórios não-esteroides com foco no seu uso na dengue.Dentro deste contexto, a Sociedade Brasileira de Hepatologia organizou uma sessão durante todo o dia 05 de agosto para discutir unicamente estes temas.
Assuntos
Hepatopatias/tratamento farmacológico , Intoxicação , Ácido Ursodesoxicólico , Anti-Inflamatórios não Esteroides , Epidemiologia , Medicamento Fitoterápico , Medicamentos Hepatoprotetores , Homeopatia , Hepatopatias , Acetaminofen/toxicidadeAssuntos
Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Receptores de Serotonina , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Olanzapina , Receptores de Serotonina/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
Rosiglitazone is an effective therapy for type 2 diabetes although concerns have grown about the incidence of oedema and cardiovascular adverse events in patients treated with the drug. The following review was conducted to evaluate further and complement the evidence linking rosiglitazone with an increased risk for cardiovascular adverse events by examining trials and case reports not included in recent meta-analyses. Rosiglitazone-related publications describing case reports and prospective and retrospective cohort analyses were identified using MEDLINE and EMBASE, from July 1999 to July 2007. Relevant reports cited in these publications were also obtained. A recently-published meta-analysis and a double-blind, randomized, placebo-controlled trial were also reviewed. This review of 20 case reports and 10 uncontrolled studies supports the need for added vigilance when prescribing rosiglitazone to patients for the treatment of type 2 diabetes who may be at risk for congestive heart failure. Clinical data from numerous case reports and uncontrolled studies suggested that patients receiving rosiglitazone should be monitored for the development of weight gain or oedema. Prudence should be observed in patients with a history or risk factors for congestive heart failure as they may be poor candidates for rosiglitazone therapy.
Assuntos
Doenças Cardiovasculares/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Tiazolidinedionas/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Edema/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Seleção de Pacientes , Fatores de Risco , Rosiglitazona , Tiazolidinedionas/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVES: We will describe insulin and C-peptide levels observed in sulfonylurea-induced hypoglycemia and determine whether these levels differed if obtained before or after hypoglycemic therapy. METHODS: We performed a systematic review of the English literature to identify Medline articles containing "sets" (glucose <60 mg/dL with insulin and C-peptide levels). These "sets" were categorized as being obtained BEFORE, AFTER, or UNKNOWN with respect to hypoglycemic therapy. RESULTS: 22 articles, 76 patients, and 97 "sets" were included. Mean glucose (mg/dL), insulin (muIU/mL), and C-peptide (ng/mL) for all "sets' were 28.6 (+/-12.6; 26.1 to 31.2), 54.4 (+/-126.3; 28.3 to 80.5), 7.2 (+/-6.2; 5.9 to 8.5). The BEFORE measures were 24.3 (+/-7.3; 18.7 to 30.0), 36.6 (+/-26.2; 16.5 to 56.7), 5.4 (+/-4.6; 1.5 to 9.2). The AFTER measures were 33.1 (+/-9.8; 28.2 to 38.0), 126.7 (+/-278.1; 0 to 265.0), 10.3 (+/-10.5; 5.1 to 15.4). The UNKNOWN measures were 28.0 (+/-13.5; 24.7 to 31.3), 37.1 (+/-21.8; 31.7 to 42.5), 6.5 (+/-4.3; 5.4 to 7.6). Only one "set" (glucose 49 mg/dL) had insulin <3.9 muIU/mL and C-peptide <1.4 ng/mL. CONCLUSIONS: Insulin > or =3.9 muIU/mL, C-peptide > or =1.4 ng/mL, and glucose <49 mg/dl are consistent with sulfonylurea-induced hypoglycemia. BEFORE levels were lower, but they were consistent with sulfonylurea-induced hypoglycemia.
Assuntos
Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Compostos de Sulfonilureia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipoglicemia/sangue , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Regulação para CimaAssuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Dióxido de Silício/efeitos adversos , Silicose/fisiopatologia , Minas de Carvão , Humanos , National Institute for Occupational Safety and Health, U.S. , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Dispositivos de Proteção Respiratória , Dióxido de Silício/química , Silicose/complicações , Silicose/prevenção & controle , Estados Unidos , United States Occupational Safety and Health AdministrationRESUMO
Brugada syndrome is a genetic dysfunction of the myocardial sodium channel that leads to ventricular dysrhythmias. The electrocardiographic (ECG) pattern of Brugada syndrome is occasionally seen after tricyclic antidepressant (TCA) ingestion; however, the outcome and complication risk for these patients is not clear. The objective of our study was to describe the incidence of Brugada ECG pattern (BEP) and serious complications of these patients in a large case series of intentional TCA ingestions. We also compared the proportion of complications of patients with BEP versus those without BEP. We evaluated 402 TCA ingestions, of which 9 (2.3%) were associated with the development of BEP. We compared the adverse outcomes of all TCA ingestions versus TCA ingestions with BEP. A increase in the adverse outcomes in the BEP group was found: seizures (relative risk [RR] 4; 95% confidence interval [CI] 1.5 to 10.8), widened QRS (RR 4.8; 95% CI 1.8 to 12.9), and hypotension (RR 3.9; 95% CI 2.1 to 7.4). To reduce confounding ingestants, we also compared all patients with an isolated TCA ingestion versus those with BEP. A significant increase in adverse outcomes was again found with the BEP group: seizures (RR 3; 95% CI 1.1 to 8.6), widened QRS (RR 4.8; 95% CI 1.5 to 15.1), and hypotension (RR 3.4; 95% CI 1.9 to 22.3). No deaths or dysrhythmias were found in the BEP group. In conclusion, BEP after TCA ingestion is rare, and death or dysrhythmias did not occur. However, patients with BEP are likely at increased risk for TCA-induced complications.
Assuntos
Antidepressivos Tricíclicos/efeitos adversos , Síndrome de Brugada , Eletrocardiografia/efeitos dos fármacos , Intenção , Adulto , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/epidemiologia , Síndrome de Brugada/fisiopatologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To assess possible cardiovascular risks associated with use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: MEDLINE and EMBASE were searched from January 1985 through April 2007 and relevant studies were retrieved. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, prospective, double-blind, case-control, and cohort-design studies published in the English language literature were considered eligible for review. Previous meta-analyses and systematic reviews were also analyzed. In total, 17 case-control studies; 9 cohort studies; 1 prospective, double-blind study; 3 meta-analyses; and 1 systematic review of observational studies were identified. DATA SYNTHESIS: Three studies were prospective and the remainder consisted of observational, retrospective studies, with most reporting acute fatal or nonfatal myocardial infarction as the cardiovascular endpoint. Among the nonselective NSAIDs, diclofenac appears to pose the highest risk for cardiovascular toxicity; other agents trend toward a neutral effect with respect to cardiovascular risk. Although the data are suggestive, it remains unclear whether naproxen provides protective cardiovascular effects among patients on chronic therapy. CONCLUSIONS: Currently available data are insufficient for defining evidence-based clinical guidelines for the use of NSAIDs, and the need for additional research, specifically randomized controlled trials, is evident. Diclofenac demonstrates a significant risk while naproxen appears to pose the lowest, albeit nonsignificant, risk for cardiovascular morbidity. Although the current clinical evidence may not warrant recommending naproxen as the preferred NSAID treatment, it may be prudent to avoid diclofenac for patients with cardiovascular risk factors requiring NSAID treatment.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Anti-Inflamatórios não Esteroides/farmacologia , Doenças Cardiovasculares/metabolismo , Humanos , Fatores de RiscoRESUMO
This report describes a Brugada electrocardiographic pattern after tricyclic antidepressant intoxication that fails to resolve following sodium bicarbonate treatment. A 50-year-old male ingested 13.6 grams of amitriptyline and presented in cardiopulmonary arrest. After initial resuscitation, the patient developed a Brugada electrocardiographic pattern. The pattern persisted despite intravenous administration of 700 mEq of sodium bicarbonate. Five hours after the last dose of sodium bicarbonate and 18 hours after initial presentation, the Brugada pattern resolved. No co-ingestants were ingested and an ischemic pattern was not seen on electrocardiogram. The serum amitriptyline level was >1000 ng/ml. Response of the tricyclic-induced Brugada pattern to sodium bicarbonate has not been previously reported.
Assuntos
Amitriptilina/intoxicação , Antidepressivos Tricíclicos/intoxicação , Síndrome de Brugada/tratamento farmacológico , Bicarbonato de Sódio/uso terapêutico , Amitriptilina/sangue , Antidepressivos Tricíclicos/sangue , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/metabolismo , Overdose de Drogas , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Bicarbonato de Sódio/administração & dosagem , Canais de Sódio/metabolismo , Falha de TratamentoRESUMO
Contrast sensitivity (CS) emerged more than 30 years ago as an alternative to traditional acuity testing, and recently it has become the focus of attention in the field of neurotoxicology. CS testing may be useful for detecting defects in oculoneural processing and therefore possible chemical-induced neurotoxicity, such as solvent-induced encephalopathy. The authors' objective in this article is to introduce the concept of CS and CS testing, summarize recent reports describing its use in occupational and environmental toxicology, and challenge the validity of CS testing in its present state as a toxicological assessment. Although CS testing appears to be an attractive and cost-effective screening tool for identifying possible neurotoxicity, additional work will be required before it can become a meaningful and widely accepted diagnostic tool.
Assuntos
Síndromes Neurotóxicas/diagnóstico , Exposição Ocupacional/efeitos adversos , Testes Visuais/métodos , Acuidade Visual/efeitos dos fármacos , Ecotoxicologia , Humanos , Metais Pesados/efeitos adversos , Compostos Orgânicos/efeitos adversosRESUMO
The liver and kidneys are tissues with a rich blood supply. Thus, with significant exposures, these tissues may be at risk for anatomic or pathophysiologic alterations. It is important to understand the gross, microscopic, and functional anatomy of these important organs to analyze potential adverse effects of solvents.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Nefropatias/induzido quimicamente , Solventes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/fisiopatologia , Humanos , Rim/fisiologia , Nefropatias/fisiopatologia , Fígado/fisiologiaRESUMO
Inhalation of fluoropolymer pyrolysis products causes a self-limited illness termed polymer fume fever; symptoms include fever, chills, myalgias and non-productive cough, and are easily mistaken for an acute viral illness. We report a 29-y-old male who developed fever and pneumonitis shortly after the inhalation of pyrolyzed hairspray. Chest x-rays showed pictures consistent with pneumonitis. The patient was treated solely with supplemental oxgen, and his symptoms resolved over 24 h. Inhalation of pyrolyzed hairspray may cause a syndrome resembling polymer fume fever.
Assuntos
Fluorocarbonos/intoxicação , Preparações para Cabelo/intoxicação , Exposição por Inalação , Pneumonia/induzido quimicamente , Adulto , Febre/etiologia , Fluorocarbonos/administração & dosagem , Humanos , Masculino , Oxigenoterapia , Polímeros , SíndromeRESUMO
This article presents the current knowledge and clinical applications of the use of biomarkers of exposure to the halogenated solvents 1,1,1 trichloroethane (methylchloroform), trichloroethylene, tetrachloroethylene (perchloroethylene), and 1,1 dichloroethylene (vinylidene chloride). Although some studies have shown that protein and DNA adducts may form with chlorinated hydrocarbons, their application has not been validated sufficiently to justify their use as biologic markers of exposure.
Assuntos
Dicloroetilenos/análise , Exposição Ambiental/análise , Solventes/análise , Tetracloroetileno/análise , Tricloroetanos/análise , Biomarcadores , Dicloroetilenos/farmacocinética , Humanos , Solventes/farmacocinética , Tetracloroetileno/farmacocinética , Tricloroetanos/farmacocinéticaRESUMO
Vapor intrusion must be recognized appropriately as a separate pathway of contamination. Although many issues resemble those of other forms of contamination (particularly its entryway, which is similar to that of radon seepage), vapor intrusion stands apart as a unique risk requiring case-specific action. This article addresses these issues and the current understanding of the most appropriate and successful remedial actions.
Assuntos
Poluentes Atmosféricos/química , Planejamento Ambiental , Exposição Ambiental/prevenção & controle , Solventes/química , Dicloroetilenos/efeitos adversos , Dicloroetilenos/química , Guias como Assunto , Humanos , Tolueno/efeitos adversos , Tolueno/química , Estados Unidos , VolatilizaçãoRESUMO
Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are synthetic amphetamine analogs that have become increasingly popular, particularly among adolescents and young adults. Many deleterious physiologic effects arising from the use of these agents have been well documented in the medical literature. Urinary retention, however, has rarely been reported as an effect of MDMA or methamphetamine use and is thought to occur as a result of alpha-adrenoceptor stimulation of the bladder neck. We report a case of acute, transient urinary retention due to combined MDMA and methamphetamine use with laboratory confirmation.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/complicações , Serviços Médicos de Emergência/métodos , Metanfetamina/intoxicação , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Retenção Urinária/induzido quimicamente , Retenção Urinária/terapia , Doença Aguda , Adolescente , Consumo de Bebidas Alcoólicas/efeitos adversos , Humanos , Masculino , Resultado do Tratamento , Cateterismo UrinárioRESUMO
Calcium channel blockers (CCB) and beta-blockers (BB) account for approximately 40% of cardiovascular drug exposures reported to the American Association of Poison Centers. However, these drugs represent >65% of deaths from cardiovascular medications. Yet, caring for patients poisoned with these medications can be extremely difficult. Severely poisoned patients may have profound bradycardia and hypotension that is refractory to standard medications used for circulatory support.Calcium plays a pivotal role in cardiovascular function. The flow of calcium across cell membranes is necessary for cardiac automaticity, conduction and contraction, as well as maintenance of vascular tone. Through differing mechanisms, CCB and BB interfere with calcium fluxes across cell membranes. CCB directly block calcium flow through L-type calcium channels found in the heart, vasculature and pancreas, whereas BB decrease calcium flow by modifying the channels via second messenger systems. Interruption of calcium fluxes leads to decreased intracellular calcium producing cardiovascular dysfunction that, in the most severe situations, results in cardiovascular collapse.Although, CCB and BB have different mechanisms of action, their physiological and toxic effects are similar. However, differences exist between these drug classes and between drugs in each class. Diltiazem and especially verapamil tend to produce the most hypotension, bradycardia, conduction disturbances and deaths of the CCB. Nifedipine and other dihydropyridines are generally less lethal and tend to produce sinus tachycardia instead of bradycardia with fewer conduction disturbances.BB have a wider array of properties influencing their toxicity compared with CCB. BB possessing membrane stabilising activity are associated with the largest proportion of fatalities from BB overdose. Sotalol overdoses, in addition to bradycardia and hypotension, can cause torsade de pointes. Although BB and CCB poisoning can present in a similar fashion with hypotension and bradycardia, CCB toxicity is often associated with significant hyperglycaemia and acidosis because of complex metabolic derangements related to these medications. Despite differences, treatment of poisoning is nearly identical for BB and CCB, with some additional considerations given to specific BB. Initial management of critically ill patients consists of supporting airway, breathing and circulation. However, maintenance of adequate circulation in poisoned patients often requires a multitude of simultaneous therapies including intravenous fluids, vasopressors, calcium, glucagon, phosphodiesterase inhibitors, high-dose insulin, a relatively new therapy, and mechanical devices. This article provides a detailed review of the pharmacology, pathophysiology, clinical presentation and treatment strategies for CCB and BB overdoses.