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BACKGROUND: Intranasal naloxone is commonly used to treat prehospital opioid overdose. However, the optimal dose is unclear, and currently, no study exists comparing the clinical effect of intranasal naloxone at different doses. OBJECTIVE: The goal of this investigation was to compare the safety, efficacy, and cost of 0.4- versus 2-mg intranasal naloxone for treatment of prehospital opioid overdose. METHODS: A retrospective, cross-sectional study was performed of 218 consecutive adult patients receiving intranasal naloxone in 2 neighboring counties in Southeast Michigan: one that used a 0.4-mg protocol and one that used a 2-mg protocol. Primary outcomes were response to initial dose, requirement of additional dosing, and incidence of adverse effects. Unpooled, 2-tailed, 2-sample t-tests and χ2 tests for homogeneity were performed with statistical significance defined as P <0.05. RESULTS: There was no statistically significant difference between the 2 populations in age, mass, gender, proportion of exposures suspected as heroin, response to initial dose, required redosing, or total number of doses by any route. The overall rate of adverse effects was 2.1% under the lower-dose protocol and 29% under the higher-dose protocol (P < 0.001). The lower-dose protocol was 79% less costly. CONCLUSION AND RELEVANCE: Treatment of prehospital opioid overdose using intranasal naloxone at an initial dose of 0.4 mg was equally effective during the prehospital period as treatment at an initial dose of 2 mg, was associated with a lower rate of adverse effects, and represented a 79% reduction in cost.
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Overdose de Drogas , Serviços Médicos de Emergência , Overdose de Opiáceos , Administração Intranasal , Adulto , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Overdose de Drogas/tratamento farmacológico , Humanos , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Estudos RetrospectivosRESUMO
This update to the 2013 joint position statement, Appropriate and Safe Utilization of Helicopter Emergency Medical Services, provides guidance for air medical services utilization based on currently available evidence. Air medical services utilization considerations fall into three major categories: clinical considerations, safety considerations, and system integration and quality assurance.Clinically, air medical services should accomplish one or more of three primary patient-centered goals: initiation or continuation of locally unavailable advanced or specialty care; expedited delivery to definitive care for time-sensitive interventions; and/or extraction from physically remote or otherwise inaccessible locations that limit timely access to necessary care. Ground-EMS (GEMS) transport is preferred when it is able to provide the necessary level of care and timely transport to definitive care.Risk identification and safety of both the patient and crew must be uniformly balanced against the anticipated degree of patient medical benefit. While auto-ready and auto-launch practices may increase access to air medical services, they also risk over-use, and so must be rigorously reviewed. Safety is enhanced during multi-agency emergency responses by coordinated interagency communication, ideally through centralized communication centers. Helicopter shopping and reverse helicopter shopping both create significant safety risks and their use is discouraged.Regional EMS systems must integrate air medical services to facilitate appropriate utilization in alignment with the primary patient goals while being cognizant of local indications, resources, and needs. To maximize consistent, informed air medical services utilization decisions, specific indications for and limitations to air medical services utilization that align with local and regional system and patient needs should be identified, and requests routed through centralized coordinating centers supported by EMS physicians.To limit risk and promote appropriate utilization of air medical services, GEMS clinicians should be encouraged to cancel an air medical services response if it is not aligned with at least one of the three primary patient-centered goals. Similarly, air medical services clinicians should be empowered to redirect patient transport to GEMS. Air medical services should not routinely be used solely to allow GEMS to remain in their primary service area.
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Resgate Aéreo , Serviços Médicos de Emergência , Aeronaves , Utilização de Instalações e Serviços , Humanos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol PropiônicoRESUMO
BACKGROUND: Brugada pattern on electrocardiography (ECG) can manifest as type 1 (coved pattern) and type 2 (saddleback pattern). Brugada syndrome represents an ECG with Brugada pattern in a patient with symptoms or clinical factors, including syncope, cardiac arrest, ventricular dysrhythmias, and family history. Brugada syndrome is caused by a genetic channelopathy, but the Brugada pattern may be drug-induced. Epinephrine-induced Brugada pattern has not been reported previously. CASE REPORT: A 63-year-old man developed anaphylaxis secondary to a bee sting, had a transient loss of consciousness, and self-administered intramuscular epinephrine. He subsequently presented to the emergency department and was found to have a type 1 Brugada pattern on ECG that resolved during observation. A historic ECG was reviewed that demonstrated a baseline type 2 Brugada pattern. His anaphylaxis was managed with steroids and antihistamines. He was observed without subsequent dysrhythmic events on telemetry or any further symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The differential diagnosis for syncope includes dysrhythmia, such as Brugada syndrome. Among other possible drugs, epinephrine may induce a type 1 Brugada pattern. Patients with Brugada pattern on ECG should be referred immediately to electrophysiology for consideration of implantation of a cardioverter-defibrillator device, given the association of Brugada pattern with sudden cardiac arrest and ventricular dysrhythmias.
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Anafilaxia/tratamento farmacológico , Síndrome de Brugada/diagnóstico , Epinefrina/efeitos adversos , Venenos de Abelha/efeitos adversos , Síndrome de Brugada/diagnóstico por imagem , Eletrocardiografia/métodos , Epinefrina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.
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Deletions of the long arm of chromosome 18 have been previously reported in many patients. Most cases involve the more distal regions of the long arm (18q21.1->qter). However, proximal interstitial deletions involving 18q11.2 are extremely rare. Here we report on a 14-month-old female with a 4.7 Mb (19,667,062-24,401,876 hg19) de novo interstitial deletion within chromosomal band 18q11.2, which includes GATA6 and 24 other RefSeq genes. The clinical features of our patient include complex congenital heart defects, a double outlet right ventricle, a subaortic ventricular septal defect, D-malposed great arteries, an atrial septal defect, a dysplastic aortic valve and patent ductus arteriosus. In addition, she had renal anomalies-a duplicated collecting system on the left and mild right hydronephrosis. These heart and renal defects are not reported in other patients with 18q proximal interstitial deletions. Heterozygous point mutations in GATA6, encoding for a zinc finger transcription factor, have been shown to cause congenital heart defects. Given the well-established biological role of GATA6 in cardiac development, a deletion of GATA6 is very likely responsible for our patient's complex congenital heart defects. This is the smallest and most proximal 18q11.2 deletion involving GATA6 that is associated with complex congenital heart disease and renal anomalies.
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Transtornos Cromossômicos/genética , Cardiopatias Congênitas/genética , Rim/anormalidades , Deleção Cromossômica , Transtornos Cromossômicos/etiologia , Cromossomos Humanos Par 18/genética , Feminino , Fator de Transcrição GATA6/genética , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
PURPOSE: To estimate the prevalence of, risk factors for, and clinical course of neuropathic pain (NPP) after sagittal split ramus osteotomy (SSRO) of the mandible in a large cohort of patients. MATERIALS AND METHODS: A retrospective cohort of all patients who underwent SSRO at 2 medical centers within Kaiser Permanente Northern California from January 2007 through September 2012 was assembled. Demographic, clinical, and surgical factors were abstracted from medical records and relevant comorbidities were identified. The prevalence of NPP in the cohort was calculated and the clinical signs, symptoms, temporal characteristics, and treatment response in affected patients were noted. RESULTS: The authors identified 1,778 patients who underwent SSRO and excluded 107 patients according to predefined criteria. The remaining 1,671 patients had a median age of 24 years (interquartile range, 19 to 35 yr) and 62.4% were women. Seven patients developed NPP after SSRO, which was an overall prevalence of 0.42%. All patients with NPP in this cohort were women and had a median age of 49 years. The risk factors for developing NPP after this surgery were older age (P = .0098), depression (P = .0100), and female gender. NPP developed an average of 30 days postoperatively (range, 18 to 56 days) and persisted for a median duration of 52 days (range, 30 to 69.5 days). All patients responded favorably to anticonvulsant (n = 6) or tricyclic (n = 1) medications, and no patients developed chronic postsurgical pain. CONCLUSIONS: NPP was an infrequent complication after SSRO, occurring in 1 of 238 patients in this cohort. The short duration and positive response to medication are reassuring findings. The results of this investigation highlight the need for prospective studies to further understand the spectrum of postoperative NPP.
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Dor Facial/etiologia , Fraturas Mandibulares/cirurgia , Neuralgia/etiologia , Osteotomia Sagital do Ramo Mandibular/efeitos adversos , Dor Pós-Operatória/etiologia , Adulto , Fatores Etários , Aminas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Estudos de Coortes , Ácidos Cicloexanocarboxílicos/uso terapêutico , Depressão/complicações , Dor Facial/tratamento farmacológico , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transtornos de Sensação/tratamento farmacológico , Transtornos de Sensação/etiologia , Fatores Sexuais , Adulto Jovem , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A(2) to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved.
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Sistema Enzimático do Citocromo P-450/metabolismo , Eicosanoides/metabolismo , Poluentes Ambientais/toxicidade , Dibenzodioxinas Policloradas/análogos & derivados , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/genética , Eicosanoides/sangue , Feminino , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Dibenzodioxinas Policloradas/toxicidade , RNA/química , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Organismos Livres de Patógenos Específicos , Baço/efeitos dos fármacos , Baço/metabolismo , Espectrometria de Massas em TandemRESUMO
CYP2S1 is a recently described dioxin-inducible cytochrome P450. We previously demonstrated that human CYP2S1 oxidizes a number of carcinogens but only via the peroxide shunt. In this article, we investigated whether human CYP2S1 can metabolize cyclooxygenase- and lipoxygenase-derived lipid peroxides in a NADPH-independent fashion. Human CYP2S1 metabolizes prostaglandin G(2) (PGG(2)) (K(m) = 0.267 ± 0.072 µM) into several products including 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT). It also metabolizes prostaglandin H(2) (PGH(2)) (K(m) = 11.7 ± 2.8 µM) into malondialdehyde, 12-HHT, and thromboxane A(2) (TXA(2)). The turnover to 12-HHT by human CYP2S1 (1.59 ± 0.04 min(-1)) is 40-fold higher than that of TXA(2) (0.04 min(-1)). In addition to PGG(2) and PGH(2) metabolism, human CYP2S1 efficiently metabolizes the hydroperoxyeicosatetraenoic acids (5S-, 12S-, and 15S-) and 13S-hydroperoxyoctadecadienoic acid into 5-oxo-eicosatetraenoic acid (turnover = 16.7 ± 0.3 min(-1)), 12-oxo-eicosatetraenoic acid 1 (11.5 ± 0.9 min(-1)), 15-oxo-eicosatetraenoic acid (16.9 ± 0.8 min(-1)), and 13-octadecadienoic acid (20.2 ± 0.9 min(-1)), respectively. Other cytochromes P450 such as CYP1A1, 1A2, 1B1, and 3A4 underwent similar conversions but at slower rates. The fatty acid hydroperoxides were also converted by human CYP2S1 to several epoxyalcohols. Our data indicate that fatty acid endoperoxides and hydroperoxides represent endogenous substrates of CYP2S1 and suggest that the enzyme CYP2S1 may play an important role in the inflammatory process because some of the products that CYP2S1 produces play important roles in inflammation.
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Sistema Enzimático do Citocromo P-450/fisiologia , Eicosanoides/metabolismo , Lipoxigenase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Biotransformação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Microssomos/enzimologia , Estrutura Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Espectrometria de Massas em Tandem , TransfecçãoRESUMO
The aryl hydrocarbon receptor (AhR) mediates induction of CYP1A1 and CYP1B1 by 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (dioxin) via binding to xenobiotic-responsive elements (XREs) in their enhancer regions. CYP1A1 and CYPIB1 were both inducible by dioxin in human MCF-7 cells. However, only CYP1A1 was inducible in human HepG2 cells. Further experiments focused on providing an explanation for this last observation. Dioxin induced the recruitment of AHR and the transcriptional coactivators p300 and p300/cAMP response element-binding protein binding protein-associated factor (PCAF) to the CYP1B1 enhancer in HepG2 cells but failed to induce recruitment of RNA polymerase II (polII) or the TATA binding protein (TBP) and acetylations of histones 3 and 4 or methylation of histone 3 at the promoter. Because p300 was required for dioxin induction of the aforementioned histone modifications at the CYP1B1 promoter and for induction of CYP1B1 transcription (in MCF-7 cells), the recruitments of p300 and AhR, although necessary, are not sufficient for eliciting the above responses to dioxin. Cytosine residues within CpG dinucleotides at the enhancer, including those within the XREs, were partially methylated, whereas those at the promoter were fully methylated. Treatment of HepG2 cells with 5-aza-2'-deoxycytidine led to partial demethylation of the promoter, restored polII and TBP binding, and CYP1B1 inducibility. Thus, the deficiency of CYP1B1 induction in HepG2 cells is ascribable to cytosine methylation at the promoter, which prevents recruitment of TBP and polII. It is noteworthy that our data indicate that stable recruitment of p300 and PCAF to the CYP1B1 gene does not require their tethering to the promoter and to the enhancer.
Assuntos
Citocromo P-450 CYP1A1/biossíntese , Sistema Enzimático do Citocromo P-450/biossíntese , Epigênese Genética/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Dibenzodioxinas Policloradas/farmacologia , Hidrocarboneto de Aril Hidroxilases , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1 , Sistema Enzimático do Citocromo P-450/genética , Dioxinas/farmacologia , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/genética , Epigênese Genética/fisiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , HumanosRESUMO
Human cytochrome P450 2S1 was recently identified and shown to be inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin and hypoxia. It is highly expressed in epithelial cells of tissues that are exposed to the environment and in many tumors of epithelial origin. The biological function of CYP2S1 has not yet been determined, although its possible role in carcinogen metabolism has been suggested. In this report, we investigated its ability to metabolize carcinogens. To obtain a large quantity of active enzyme for substrate screening, we overexpressed CYP2S1 in Escherichia coli (200 nM culture), using a synthetic gene approach. High-level expression allowed us to achieve purification of CYP2S1 with high specific content and purity (16 nmol/mg). Despite high-level expression, we found that CYP2S1 was not readily reduced by cytochrome P450 reductase, and thus no activity was found using NADPH. However, the oxidative activity of CYP2S1 was supported by cumene hydroperoxide or H(2)O(2), such that CYP2S1 oxidized many important environmental carcinogens, including benzo[a]pyrene, 9,10-dihydro-benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene-7,8-dihydrodiol, aflatoxin B1, naphthalene, and styrene, with high turnover. Most substrates tested were converted to detoxification products, except in the case of benzo[a]pyrene-7,8-dihydrodiol, which was converted into the very potent carcinogenic metabolite 7,8-dihydrodiol-trans-9,10-epoxide at a relatively efficient rate (K(m) = 12.4 +/- 2 microM, turnover = 2.3 min(-1)). This metabolite formation was also supported both in vitro and in vivo by fatty acid hydroperoxides described in the accompanying report (p. 1044). Together, these data indicate that CYP2S1 contributes to the metabolism of environmental carcinogens via an NADPH independent activity.
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Sistema Enzimático do Citocromo P-450/fisiologia , Proteínas de Escherichia coli/fisiologia , Escherichia coli/enzimologia , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Genes Sintéticos/fisiologia , Sequência de Aminoácidos , Carcinógenos Ambientais/metabolismo , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/genética , Humanos , Dados de Sequência Molecular , NADP/fisiologia , TransfecçãoRESUMO
In the accompanying report (p. 1031), we showed that a novel dioxin-inducible cytochrome P450, CYP2S1, efficiently metabolizes benzo[a]pyrene-trans-7,8-dihydrodiol (BaP-7,8-diol) into the highly mutagenic and carcinogenic benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BaP-diol-t-epoxide), using cumene hydroperoxide in lieu of NADPH/O(2). Lipid hydroperoxide-supported P450 oxidation has been reported in several cases. However, it has not yet been described for the bioactivation of BaP-7,8-diol. In this report, we demonstrate that CYP2S1 can use various fatty acid hydroperoxides to support epoxidation of BaP-7,8-diol at a much higher rate than with cumene hydroperoxide. Kinetic analyses with several fatty acid hydroperoxides revealed that 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE) was the most potent oxidant tested (K(m), 3.4 +/- 0.8 microM; turnover, 4.51 +/- 0.13 min(-1)), followed by 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (K(m), 2.8 +/- 0.7 microM; turnover, 3.7 +/- 0.1 min(-1)), 5S-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (K(m), 2.7 +/- 0.8 microM; turnover, 3.69 +/- 0.09 min(-1)), and 15S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (K(m), 11.6 +/- 0.3 microM; turnover, 0.578 +/- 0.030 min(-1)). The antioxidant butylated hydroxyanisole inhibited CYP2S1-catalyzed epoxidation by 100%, suggesting that epoxidation proceeds by a free radical mechanism. Other cytochromes P450, including CYP1A1, CYP1B1, CYP1A2, and CYP3A4, were also able to epoxidize BaP-7,8-diol using various fatty acid hydroperoxides, although at slower rates than CYP2S1. The cytotoxicity of BaP-7,8-diol significantly increased in mammalian cells overexpressing CYP2S1, and BaP-diol-t-epoxide formation in these cells also increased in the presence of 13-HpODE. Together, these results suggest that fatty acid hydroperoxides can serve as physiological cofactors in supporting in vivo CYP2S1-catalyzed oxidation of BaP-7,8-diol, and that fatty acid hydroperoxides and CYP2S1 may play important roles in benzo[a]pyrene-induced carcinogenesis.
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Sistema Enzimático do Citocromo P-450/fisiologia , Di-Hidroxi-Di-Hidrobenzopirenos/metabolismo , Peróxidos Lipídicos/metabolismo , Animais , Biotransformação , Linhagem Celular Tumoral , Células Cultivadas , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Di-Hidroxi-Di-Hidrobenzopirenos/química , Poluentes Ambientais/metabolismo , Humanos , Peróxidos Lipídicos/química , Camundongos , OxirreduçãoRESUMO
PURPOSE: The aim of this study was to determine the rate of postoperative infection and the efficacy of removing teeth in the line of mandibular angle fractures treated with 2.0-mm 8-hole titanium curved strut plates. Our understanding is that this method of repair is currently being used only in a few centers in the United States. MATERIALS AND METHODS: A retrospective review of mandibular angle fractures treated with a 2.0-mm 8-hole strut plate during a 4-year period. Postoperative antibiotics were given for 1 week. Follow-up appointments were 4 weeks or longer. A nonchewing diet was instructed for 6 weeks. Data for all selected patients include the information such as age, gender, etiology of injuries, medical history, concurrent injuries, nerve deficits, pre- and postoperative antibiotic administration, postop infection, a presence or absence of teeth in the line of fractures, and whether these teeth were removed. RESULTS: Four patients (4 of 49 or 8.2%) developed infections. Two of those patients had a tooth in the line of a fracture that was retained (2 of 14 or 14%). The third had a tooth in the line of a fracture that was extracted (1 of 18 or 5.6%). The fourth patient was 1 of the 17 patients who did not have teeth in the line of fracture and developed infection (1 of 17 or 5.9%). None of the patients developed failed hardware, malunion, nonunion, malocclusion, or iatrogenic nerve injury. CONCLUSIONS: The use of a 2.0-mm 8-hole strut plate is associated with a low infection rate (8.2%). The infection rate for those mandibular angle fractures with teeth in the line of fracture retained was 14% compared with 5.6% for those fractures with the teeth in the line of fracture extracted.
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Placas Ósseas , Fraturas Mandibulares/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Parafusos Ósseos , Dieta , Desenho de Equipamento , Feminino , Seguimentos , Fixação Interna de Fraturas/instrumentação , Humanos , Técnicas de Fixação da Arcada Osseodentária , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dente/patologia , Extração Dentária , Resultado do Tratamento , Violência , Adulto JovemRESUMO
Introduction. Terbinafine is reported to be associated with rhabdomyolysis. We present a patient taking terbinafine who may have developed exercise-induced rhabdomyolysis. Case Report. A healthy 40-year-old female developed onychomycosis of the right first toe for which she was taking terbinafine. After an increase in her exercise regimen, she began experiencing notable myalgias of the triceps. During outpatient evaluation, the patient was found to have elevated and worsening creatine kinase (CK) and aspartate transaminase. At evaluation in the emergency department, CK was <5000 IU/L and had decreased. She did not have electrolyte abnormalities, kidney injury or kidney failure. Discussion. Patients may be at risk for exercise-induced rhabdomyolysis while on terbinafine and may need to be cautioned regarding the intensity of exercise.
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A novel mibefradil derivative, NNC55-0396, designed to be hydrolysis-resistant, was shown to be a selective T-type Ca(2+) channel inhibitor without L-type Ca(2+) channel efficacy. However, its effects on cytochromes P450 (P450s) have not previously been examined. We investigated the inhibitory effects of NNC55-0396 toward seven major recombinant human P450s--CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C8, CYPC19, and CYP2E1--and compared its effects with those of mibefradil and its hydrolyzed metabolite, Ro40-5966. Our results show that CYP3A4 and CYP2D6 are the two P450s most affected by mibefradil, Ro40-5966, and NNC55-0396. Mibefradil (IC(50) = 33 +/- 3 nM, K(i) = 23 +/- 0.5 nM) and Ro40-5966 (IC(50) = 30 +/- 7.8 nM, K(i) = 21 +/- 2.8 nM) have a 9- to 10-fold greater inhibitory activity toward recombinant CYP3A4 benzyloxy-4-trifluoromethylcoumarin-O-debenzylation activity than NNC55-0396 (IC(50) = 300 +/- 30 nM, K(i) = 210 +/- 6 nM). More dramatically, mibefradil (IC(50) = 566 +/- 71 nM, K(i) = 202 +/- 39 nM) shows 19-fold higher inhibition of CYP3A-associated testosterone 6beta-hydroxylase activity in human liver microsomes compared with NNC55-0396 (IC(50) = 11 +/- 1.1 microM, K(i) = 3.9 +/- 0.4 microM). Loss of testosterone 6beta-hydroxylase activity by recombinant CYP3A4 was shown to be time- and concentration-dependent with both compounds. However, NNC55-0396 (K(I) = 3.87 microM, K(inact) = 0.061/min) is a much less potent mechanism-based inhibitor than mibefradil (K(I) = 83 nM, K(inact) = 0.048/min). In contrast, NNC55-0396 (IC(50) = 29 +/- 1.2 nM, K(i) = 2.8 +/- 0.3 nM) and Ro40-5966 (IC(50) = 46 +/- 11 nM, K(i) = 4.5 +/- 0.02 nM) have a 3- to 4-fold greater inhibitory activity toward recombinant CYP2D6 than mibefradil (IC(50) = 129 +/- 21 nM, K(i) = 12.7 +/- 0.9 nM). Our results suggest that NNC55-0396 could be a more favorable T-type Ca(2+) antagonist than its parent compound, mibefradil, which was withdrawn from the market because of strong inhibition of CYP3A4.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/efeitos dos fármacos , Inibidores do Citocromo P-450 CYP3A , Mibefradil/química , Citocromo P-450 CYP3A , Humanos , Hidrólise , Mibefradil/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Proteínas Recombinantes/antagonistas & inibidoresRESUMO
OBJECTIVES: We report on the rates of patient acceptance and their perceptions of routine emergency department (ED) human immunodeficiency virus (HIV) testing in a high-prevalence area. METHODS: We analyzed the race/ethnicity of patients who either accepted or declined a routine HIV test that was offered to all patients in the ED of a large academic center. We also distributed a patient perception survey about ED HIV testing. RESULTS: During the study period, an HIV screening test was offered to 9,826 patients. Of these, 5,232 patients (53%) accepted the test. The acceptance rate of HIV testing was highest among African American patients (55%), followed by 52% for white, 50% for Hispanic, and 42% for Asian patients. A total of 1,519 completed surveys were returned for analysis. The most common reasons for declining a test were that patients did not perceive themselves to be at risk for HIV (49%) or they had recently been tested for HIV (18%). Overall, 84% of patients stated they would recommend to a friend to get an HIV test in the ED. When analyzed by ethnicity, 89% of African American patients stated they would recommend to a friend to get an HIV test if the friend went to the ED, but only 74% of white patients would do so. CONCLUSIONS: The Centers for Disease Control and Prevention's 2006 recommendations on HIV screening are well accepted by the target populations. Further work at explaining the risk of HIV infection to ED patients should be undertaken and may boost the acceptance rate of ED HIV screening.
Assuntos
Sorodiagnóstico da AIDS/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Infecções por HIV/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Satisfação do Paciente , Percepção Social , Adulto , Centers for Disease Control and Prevention, U.S. , District of Columbia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Neurosarcoidosis, either isolated or as part of systemic sarcoidosis, is an uncommon entity and has diagnostic uncertainty. Treatment for neurosarcoidosis can increase the risk of infections, including fungal infections such as disseminated histoplasmosis. Neurosarcoidosis may further predispose patients to infections of the central nervous system. CASE PRESENTATION: A 54-year-old male with a history of probable neurosarcoidosis on methotrexate and infliximab presented with encephalopathy, hypoxia, and reported fevers. The patient was found to have disseminated histoplasmosis involving the lungs (miliary histoplasmosis), central nervous system (neurohistoplasmosis), and bloodstream. The Histoplasma capsulatum infection was treated with amphotericin and then voriconazole. DISCUSSION: Patients with neurosarcoidosis are suspected to have blood-brain barrier dysfunction. Lumbar puncture should be considered as part of initial investigative studies for infection. Empiric antimicrobial therapy for a patient with neurosarcoidosis on immunosuppressive agents may need to include antifungal agents.
RESUMO
Introduction. Pericardial effusion in the setting of hyperthyroidism is rare. We present a patient with Graves' disease who developed a sanguineous pericardial effusion and cardiac tamponade. Case Description. A 76-year-old man presenting with fatigue was diagnosed with Graves' disease and treated with methimazole. Two months later, he was hospitalized for uncontrolled atrial fibrillation. Electrocardiography showed diffuse low voltage and atrial fibrillation with rapid ventricular rate. Chest radiograph revealed an enlarged cardiac silhouette and left-sided pleural effusion. Thyroid stimulating hormone was undetectable, and free thyroxine was elevated. Diltiazem and heparin were started, and methimazole was increased. Transthoracic echocardiography revealed a large pericardial effusion with cardiac tamponade physiology. Pericardiocentesis obtained 1,050 mL of sanguineous fluid. The patient progressed to thyroid storm, treated with propylthiouracil, potassium iodine, hydrocortisone, and cholestyramine. Cultures and cytology of the pericardial fluid were negative. Thyroid hormone markers progressively normalized, and he improved clinically and was discharged. Discussion. We found 10 previously reported cases of pericardial effusions in the setting of hyperthyroidism. Heparin use may have contributed to the sanguineous nature of our patient's pericardial effusion, but other reported cases occurred without anticoagulation. Sanguineous and nonsanguineous pericardial effusions and cardiac tamponade may be due to hyperthyroidism.
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Introduction. 3,3'-Diindolylmethane is available as a supplement in the United States for "cancer prevention" and "augmentation of physical fitness." A derivative of indole-3-carbinol found in plants, diindolylmethane, binds to receptors associated with the sex steroid pathways and has unclear effects on estrogen and androgen physiology. We present a patient who had been taking diindolylmethane and developed right lower extremity deep venous thrombosis and bilateral pulmonary embolism. Case Presentation. A 65-year-old man presented with swelling, erythema, and warmth of his right lower extremity for three to four weeks. He had been taking diindolylmethane one tablet daily for three to four months. Risk factors for venous thromboembolism included tobacco use, personal history of possible pulmonary embolism, body mass index, and age. Imaging studies found extensive deep venous thrombosis in his right lower extremity and bilateral pulmonary embolism with probable right middle lobe infarction. Follow-up imaging showed chronic deep venous thrombosis in his right lower extremity. Discussion. As suggested in this single case, patients who take diindolylmethane may be at greater risk for venous thromboembolism. Further reports and studies are necessary in order to elucidate this possible association. Clinicians should question patients about supplements in the setting of venous thromboembolism.
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Multiple comorbidities, advanced age, tobacco use, and alcohol abuse made a proper diagnosis difficult in a patient with polyarticular septic arthritis, infectious tenosynovitis, and ruptures in the tendons of both thumbs.