19 resultados para Dose-resposta


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AIMS: Protocols using sublingual nitrates have been increasingly used to improve diagnostic accuracy of head-up tilt testing (HUT). Nevertheless, exaggerated responses to nitrates have been frequently described, particularly in elderly patients. The aim of this article is to evaluate, in an elderly population with unexplained syncope, whether the impact of sublingual nitroglycerin (NTG) used as a provocative agent is dose-dependent. METHODS AND RESULTS: One hundred and twenty consecutive elderly patients submitted to HUT using NTG after an asymptomatic drug-free phase were studied. Patients were divided into three groups according to the NTG dosage: 500, 375 and 250 microg. The test was considered positive when there was reproduction of symptoms with bradycardia and/or arterial hypotension. A gradual decrease in the blood pressure after NTG was considered an exaggerated response to nitrates. There were no differences in the clinical characteristics of the different subgroups. A positive test was obtained in 50% of the patients in each group. The rate of exaggerated responses was identical in all groups and ranged between 15 and 17%. CONCLUSION: In an elderly population with syncope of unknown origin submitted to HUT, the response to NTG is not dose-dependent, and no difference was found in the rate of exaggerated responses to nitrates with different NTG dosages.

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Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

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AIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.

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AIMS: To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). METHODS: Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. RESULTS: In patients with baseline HDL-C<40 mg.dL-1 an increase in HDL-C from 31+/-1 mg.dL-1 to 44+/-2 mg.dL-1 (95% confidence interval 5.9, 21.9, P<0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg.L-1 and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. CONCLUSIONS: There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.

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O tratamento de uma crise hipertensiva visa controlar os níveis críticos de pressão arterial até níveis hemodinâmicos seguros, que não necessariamente normais. Os autores ressaltam a necessidade para o seu correcto tratamento de um pronto diagnóstico, diferenciando as situações de menor gravidade das de verdadeira urgência hipertensiva, da compreensão da sua fisiopatologia e do conhecimento dos fármacos disponíveis.

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A braquiterapia prostática de baixa taxa de dose é considerada uma opção terapêutica adequada para o carcinoma da próstata. É habitualmente, apresentada como a melhor forma de preservar a função eréctil de entre os diversos tratamentos de carcinoma da próstata. Contudo, estudos recentes demonstram que, também a braquiterapia prostática pode, no longo prazo, provocar algum grau de disfunção eréctil (DE). As taxas de DE nas diversas séries publicadas, são muito variáveis. Os resultados da influência da dose de radiação, isoladamente (D90) ou quando incidindo sobre o feixe neurovascular ou o bulbo são contraditórios. O tipo de isótopo utilizado não tem qualquer influência sobre a DE. No entanto factores como a idade, a função eréctil pré-tratamento, a diabetes, a utilização de radioterapia externa adjuvante e/ou hormonoterapia neoadjuvante podem condicionar os resultados obtidos. Otratamento da disfunção eréctil deve ser efectuado com inibidores da fosfodiesterase, obtendo-se boas taxas de resposta. Podem surgir outras alterações da função sexual, nomeadamente, hematospermia, dor durante o orgasmo e alteração da intensidade do orgasmo.

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Em 1968 foram descritos sintomas autolimitados que surgiam até 30 minutos após refeição em restaurante chinês. Esta síndrome tem sido atribuída ao consumo de glutamato monossódico (GMS), sendo designada por “complexo de sintomas associado ao GMS”. Foi objectivo deste estudo avaliar a resposta ao GMS em dois adultos com história sugestiva de reacção adversa a este aditivo alimentar. Em ocultação simples, foram administrados oralmente, em jejum e em dias diferentes, placebo ou doses crescentes de GMS, até à dose cumulativa de 5 gramas, sendo a prova considerada positiva caso surgissem pelo menos dois sintomas de vinte descritos na literatura. Apenas a prova com GMS foi positiva num doente, que referiu mal-estar geral, astenia e hipersudorese, na dose máxima. À semelhança de outros estudos, os resultados sugerem que doses elevadas de GMS, administradas sem alimentos, podem provocar sintomas em indivíduos com história suspeita de “complexo de sintomas associado a GMS”.

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BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients treated with primary angioplasty, neutrophil response and its prognostic significance are not entirely understood. METHODS: We retrospectively studied 305 consecutive and non-selected STEMI patients. They were divided into three groups according to the maximum neutrophil percentage in the first 48 hours. We compared baseline demographic characteristics, coronary disease risk factors, cardiac history, clinical presentation, therapeutics administered and clinical evolution. We then assessed survival in the three groups and determined predictors of 30-day mortality. Group 1 (G1) had a mean age of 57 +/- 14 years and showed mean neutrophilia of 73.3%, Group 2 (G2) 61 +/- 13 years and 79.9%, and Group 3 (G3) 66 +/- 13 years and 84.2%. We compared outcomes and 30-day mortality between the groups. RESULTS: Mean age rose with increased neutrophil response. There were no statistically significant baseline differences between the groups except for more smokers in Groups 1 and 2, and more patients presenting with Killip class > or = 2 and fewer with uncomplicated evolution in Group 3. During 30-day follow-up there were 19 deaths (G1=1, G2=3 and G3=15). In univariate analysis mortality predictors were age > or = 75 years, anterior STEMI, maximum creatinine kinase > or = 2500 UI/L, culprit lesion in proximal anterior descending artery, incomplete revascularization, Killip > or = 2 at presentation, and being in G3. After multivariate regression analysis independent predictors were age > or = 75 years, incomplete revascularization and being in G3. CONCLUSION: In myocardial infarction patients undergoing mechanical revascularization, an intense neutrophil response (routinely, easily and inexpensively assessed) is related to worse short-term prognosis.

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Cardiopulmonary exercise testing (CPET) is an objective method for assessment of functional capacity and for prognostic stratification of patients with chronic heart failure (CHF). In this study, we analyzed the prognostic value of a recently described CPET-derived parameter, the minute ventilation to carbon dioxide production slope normalized for peak oxygen consumption (VE/VCO2 slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and dilated cardiomyopathy who performed maximal CPET using the modified Bruce protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared with traditional CPET parameters. RESULTS: During follow-up 37 patients died and 12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12-36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or = 2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory response to exercise for peak oxygen consumption appears to increase the prognostic value of CPET in patients with CHF.

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Os autores apresentam o caso clínico de uma criança de 18 meses, sexo masculino, raça branca,internada na Unidade de Nefrologia com o diagnóstico de síndroma nefrótico - crise inaugural. Atendendo à idade, aos parâmetros bioquímicos e estudo imunológico negativo, admite-se síndroma nefrótico de lesões mínimas e inicia corticoterapia na dose 60mg/m2/dia. Porqua às seis semanas mantinha edema refractário e comportava-se como corticorresistente, efectuou-se biópsia renal que revelou glomerunefrite membranosa com profileração de crescentes depósitos de IgG, IgA, IgM, C1, C3, C4, C1q, a favor da doença imunológica de base e sugestiva de nefropatia lúpica. O protocolo terapêutico foi revisto e iniciou terapêutica de seis ciclos mensais de ciclofosfamida endovenosa. A resposta clínica laboratorial foi favorável a partir do quarto ciclo e está em remissão após os seis ciclos efectuados e seguimento em ambulatório de 14 meses.

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Introdução: O Hemangioma infantil é o tumor benigno mais frequente na idade pediátrica. A maioria tem evolução favorável, no entanto dependendo da sua localização, podem levar à distorsão de estruturas anatómicas ou a outras complicações locais ou sistémicas, tornando necessária uma abordagem terapêutica precoce e eficaz. Neste contexto, desde que Léauté-Labréze e colaboradores publicaram a sua experiência com o propranolol em 2008, têm-se multiplicado na literatura internacional, casos clínicos e pequenas séries em que este fármaco é utilizado “off-label” como terapêutica de primeira linha. O presente trabalho visa reportar a experiência de um serviço na utilização de propranolol como terapêutica de primeira linha no tratamento do hemangioma infantil em 2 doentes. Casos clínicos: O doente 1, do sexo feminino, tinha um hemangioma infantil desde as 5 semanas, localizado na pirâmide nasal. O doente 2, do sexo masculino, tinha dois hemangiomas infantis ulcerados: um localizado na face, com atingimento do mento, lábio inferior, mucosa gengival e labial; um segundo de localização escrotal. Ambos os doentes realizaram indução terapêutica com propranolol em regime de internamento com uma dose alvo de 2 a 3 mg/Kg/dia. Ao fim de 6 meses de follow-up, assistiu-se a uma resposta muito satisfatória, sem complicações documentadas. Discussão: O propranolol constitui uma alternativa segura e eficaz no tratamento do hemangioma. Embora não tenham ocorrido complicações, elas estão descritas e ocorrem principalmente durante a fase de indução terapêutica, tornando importante a monitorização durante esse período.

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Discoid lupus erythematosus (DLE) is a chronic, indolent, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring and depigmentation. In a small number of patients, it is refractory to standard therapies. In several studies, thalidomide has been reported to be an effective treatment in those cases. The most fearful side effects are teratogenicity and neuropathy. Adequate counseling and vigilance must be given to the patients. We report a 45-year-old Portuguese woman who presented with a 20-year history of severe facial and scalp DLE confirmed by histopathology. For several years, it failed to respond to several therapies, including topical, intralesional and oral corticosteroids, hydroxychloroquine, methotrexate, azathioprine and topical tacrolimus. Thalidomide was initiated at a dosage of 50mg/day and the skin lesions had improved dramatically after three weeks with complete clinical remission. Two months later, the dose was reduced to 50mg, five days per week without disease rebound. The patient´s concomitant medications during the treatment included sunscreen, hydroxycholoroquine, enoxaparin and aspirin to prevent thromboembolic events. Pregnancy testing, routine laboratory and electrocardiography were performed at regular intervals for safety monitoring and the results were within normal limits. Only minor side effects as nausea, constipation and somnolence were noted, however, they improved with dose reduction. Our data confirm that thalidomide therapy is an alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. In this patient, low-dose thalidomide was an effective treatment with minimal side effects.

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A urticária retardada de pressão é uma forma rara de urticária física que se caracteriza pelo aparecimento de urticária e angioedema após aplicação de pressão mecânica. Na maioria dos casos está associada a urticária crónica idiopática. Difere das restantes formas de urticária pelo aparecimento tardio das lesões, pela maior duração das mesmas, que se podem prolongar para além das 24-48 horas e por uma resposta terapêutica ausente ou parcial aos anti-histamínicos H1. A sua patogénese permanece por esclarecer. Os autores apresentam o caso clínico de um doente do sexo masculino, no qual foram experimentadas diferentes abordagens terapêuticas, na tentativa de evitar o recurso a corticoterapia prolongada. Dada a ausência de resposta terapêutica aos fármacos utilizados, com excepção dos corticóides sistémicos, manteve-se a corticoterapia diária, utilizando a dose mínima eficaz para o controlo dos sintomas. Apesar de vários relatos publicados na literatura se referirem à eficácia terapêutica de diferentes fármacos no controlo desta patologia, a maioria dos doentes requer corticoterapia sistémica para alcançar o controlo sintomático.