O envolvimento dos alótipos de C4 na patogênese das doenças humanas

The complement system is an important humoral defense mechanism that plays a relevant role against microbial agents, inflammatory response control, and immunocomplex clearance. Classical complement pathway activation is antibody-dependent. The C4 component participates in the initial step of activation, and C4 expression is determined by 2 pairs of allotypes: C4A and C4B. Deficiencies in C4 allotypes have been associated with several diseases. The aim of the present review is evaluate the reported data in the literature regarding specific C4A and C4B deficiencies and characterize their clinical relevance. We searched the MEDLINE and LILACS databases. Papers referring to total C4 deficiency without allotype evaluation and case reports of primary C4 deficiency were not included. Deficiencies in C4 allotypes have been associated with Mycobacterium leprae infection, erythema nodosum, systemic sclerosis with anti-topoisomerase I antibodies, intermediate congenital adrenal hyperplasia with DR5 genotype, diabetes mellitus type 1 with DR3,4 genotype, and diabetes mellitus with antibodies against islet cells. C4 allotype deficiency is also related to C4B deficiency and autoimmune-associated diseases, such as systemic lupus erythematosus, or diseases with an autoimmune component, such as autism. Some reports associate C4A with thyroiditis after delivery as well as limited and systemic sclerosis without anti-topoisomerase I antibodies. However, the studies with C4A and C4B have been concentrated in isolated populations, and some of the studies could not be reproduced by other authors.O sistema complemento constitui um importante sistema de defesa humoral, exercendo papel relevante na resposta contra agentes microbianos, no controle da resposta inflamatória e na depuração de imunocomplexos. A ativação da via clássica é dependente da formação do complexo antígeno-anticorpo. O componente C4 do complemento participa da etapa inicial de ativação desta via e a sua expressão é determinada por dois alótipos : C4A e C4B. A deficiência dos alótipos de C4 tem sido relacionada a várias doenças. O objetivo do presente estudo foi avaliar os dados de literatura que descrevem as deficiências específicas de C4A e C4B com a finalidade de caracterizar seu significado clínico. Foi realizada uma ampla revisão bibliográfica através do MEDLINE e LILACS, avaliando-se os dados de literatura. Excluiu-se estudos com a avaliação de C4 total sem a análise dos alótipos e relatos de caso isolados de deficiência total de C4. Verificou-se que a deficiência dos alótipos de C4 está relacionada com algumas doenças: hanseníase, esclerose sistêmica com anticorpos anti-topoisomerase I, hiperplasia adrenal congênita intermediária com genótipo DR5, diabetes mellitus tipo 1 com genótipo DR3,4 e diabetes mellitus tipo 1 com anticorpos anti-células das ilhotas. Também foram observadas algumas associações entre C4B e doenças auto-imunes como lupus eritematoso sistêmico, ou que se supõe terem um componente auto-imune como o autismo. Estudos demonstraram associações do C4A com tireoidite pós-parto, esclerose limitada e esclerose sistêmica sem anticorpos anti-topoisomerase I. Porém, os estudos dos alótipos de C4 se concentraram em populações isoladas e alguns destes não conseguiram ser reproduzidos por outros autores

Efficacy of a triple therapy for Helicobacter pylori eradication in a well-developed urban area in Brazil

CONTEXT: Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. Triple therapy with omeprazole plus two antibiotics has been used. Due to the lack of ideal treatment and the high rates of primary resistance to nitroimidazoles, the use of clarithromycin has been adopted. OBJECTIVE: To determine the Helicobacter pylori eradication rates using lansoprazole, amoxicillin and clarithromycin for seven days, in patients with peptic ulcer disease in a well developed urban area in Brazil. METHODS: This was a retrospective, open-label study carried out at the School of Medicine of the Fundação ABC. It included 130 patients with peptic ulcer disease (upper endoscopy) who had been tested positive for Helicobacter pylori infection (urease test, histology or breath test), without previous treatment. Patients were treated with lansoprazole 30 mg, amoxicillin 1,000 mg and clarithromycin 500 mg b.i.d., for seven days. Eradication was verified after 90 days. RESULTS: Follow-up data were available for 94 patients. Their mean age was 52.23 years; 51.54% were woman, 84.31% white, 37.69% smokers, 20.77% using nonsteroidal anti-inflammatory drugs and 8.46% alcoholics. Upper endoscopy revealed that 78.46% had duodenal ulcers and 21.53% had gastric ulcers (a 4:1 DU:GU ratio). The eradication rates were 85.11% per protocol and 61.54% by intention to treat; 97% had no adverse effects. CONCLUSION: Triple therapy using lansoprazole, amoxicillin and clarithromycin is well tolerated with high eradication rates and forms a good alternative for developing countries

Praying correlates with higher quality of life: results from a survey on complementary/alternative medicine use among a group of Brazilian cancer patients

CONTEXT: The use of complementary/alternative medicine has been little studied in Brazil. OBJECTIVE: The purpose of this study was to determine the prevalence of complementary/alternative medicine use among a group of Brazilian cancer patients and correlate these findings with the patients' quality of life. TYPE OF STUDY: Descriptive. SETTING: Oncology Institute of the Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil. PARTICIPANTS: 100 cancer patients. PROCEDURES: The EORTC QLQ C-30 quality of life questionnaire was applied together with another questionnaire on the use of complementary/alternative medicine. MAIN MEASUREMENTS: Use of complementary/alternative medicine and quality of life. RESULTS: 89% of the patients had already used complementary/alternative medicine, 63% were currently using it and most of them (77.7%) believed in the efficacy of complementary/alternative medicine for their treatment. The type most used was individual prayer (77.5%). We found a significant association between believing in the efficacy of complementary/alternative medicine and praying (individually or in groups), in comparison with better scores on the functional (p = 0.001) and overall health (p = 0.001) quality of life scales. Multivariate analysis confirmed these findings regarding praying and also showed that believing in complementary/alternative medicine correlated significantly with functional and symptom quality of life scores. CONCLUSION: The prevalence of complementary/alternative medicine use in this group of cancer patients was high. Praying and belief in the efficacy of complementary/alternative medicine correlated significantly with an overall better quality of life, and therefore these practices should not be discouraged by physicians. New prospective studies should be conducted in order to better characterize the efficacy of such alternative therapeutic approaches

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC

CONTEXT AND OBJECTIVE: Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. DESIGN AND SETTING: Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. METHODS: From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. RESULTS: The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. CONCLUSIONS: Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug