Association Between XRCC1 and WRN as Genetic Markers of Stability and Susceptibility to Cancer in Patients with HIV/AIDS and Cancer: a Cross-Sectional Study

Background: HIV-induced immunodeficiency has been implicated as a key factor for risk of cancer. Neoplasia is considered to result from accumulation of damage to the genome. Polymorphisms in repair genes, such as the XRCC1 and WRN, have been associated with susceptibility to development of cancer in patients with HIV/AIDS. The aim of this study was to analyze the frequency of polymorphisms in XRCC1 (Arg399Gln) and WRN (Cys1367Arg) in patients with HIV/AIDS with or without cancer. Materials and Methods: Genotyping for analysis of polymorphisms was carried out by PCR (Polymerase Chain Reaction) and RFLP (Restriction Fragment Length Polymorphism). Results: In the genotypic and allelic analysis, no increased risk of cancer was observed with any genotype or allele of XRCC1 (Arg399Gln) singly (prevalence ratio 2.82; p-value= 0.24). However, with the WRN (Cys1367Arg) gene, the heterozygous genotype and arginine allele were associated with increased risk (prevalence ratio= 25.62; p-value= 0.0001). Correlation analysis showed no association between gender and the risk (male p-value= 0.639 and women p-value> 1); however, a positive association for the increased risk of cancer was shown with XRCC1 (Arg399Arg) wild-type homozygous and WRN (Cys1367Arg) heterozygous (p-value< 0.001), with heterozygous XRCC1 (Arg399Gln) and WRN (Cys1367Arg) (p-value< 0.001), and with variant homozygous XRCC1 (Gln399Gln) and heterozygous WRN (Cys1367Arg) (p-value< 0.001). Conclusions: There is no increased risk of cancer in patients who are HIV/AIDS carriers of the XRCC1 (Arg399Gln) gene singly. However, there is a high risk in patients with HIV/AIDS who have the heterozygous genotype and the arginine allele in the WRN (Cys1367Arg) gene singly. Those with WRN (Cys1367Arg) heterozygote genotype showed a high risk of cancer with all genotypes of the XRCC1 (Arg399Gln) gene.

Study of Natural Cytotoxicity Receptors in Patients with HIV/AIDS and Cancer: A Cross-Sectional Study.

The NCR receptors play a fundamental role in the cytotoxicity mediated by NK cells against tumor cells. In the current study, we investigated possible HIV/AIDS-related changes in the expression of the NCR receptors comparing healthy donors, HIV/AIDS patients, and HIV/AIDS patients with cancer (HIV/AIDSWC). The NCRs were quantified in NK cells (NK(dim) and NK(bright)) and T lymphocytes from peripheral blood samples by flow cytometry. We found a significant decrease in the frequency of NK cells expressing NKp46 in HIV/AIDS group (p = 0.0012). There was a decrease in the frequency of NK cells expressing NKp46 in the HIV/AIDSWC group; however, this was not statistically significant. We found a significant decrease in the frequency of NK cells expressing NKp30 in the HIV/AIDS group (p = 0.0144). There was a decrease in the frequency of NK cells expressing NKp30 and in the HIV/AIDSWC group, but this was not statistically significant. There were no changes in the distribution of NK cells and their subtypes in both groups.

Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20 percent. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24 percent) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.

Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients.

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.

Dislipidemia em pacientes HIV/AIDS em uso de anti-retrovirais num hospital universitário, Rio de Janeiro, Brasil / Dyslipidemia in HIV/AIDS patients in antiretroviral therapy in a university hospital, Rio de Janeiro, Brazil

INTRODUÇÃO: O uso contínuo da terapêutica anti-retroviral (TARV) está associado à ocorrência de diversos distúrbios metabólicos. OBJETIVO: O principal objetivo deste estudo foi determinar a prevalência de dislipidemia em pacientes com vírus da imunodeficiência humana/síndrome de imunodeficiência adquirida (HIV/AIDS) atendidos no ambulatório de doenças infecciosas do Hospital Universitário Pedro Ernesto da Universidade do Estado do Rio de Janeiro (HUPE/UERJ). MATERIAL E MÉTODOS: No período de 1/10/2004 a 30/5/2005, os participantes do estudo responderam a uma entrevista sobre dados demográficos e relativos à saúde. Após a entrevista foram verificadas as seguintes medidas: peso, altura, cintura e quadril. Foi coletado sangue para realização de dosagem plasmática de colesterol total (CT), colesterol da lipoproteína de alta densidade (HDL-C) e triglicerídeos (TG). Dos 268 pacientes que compareceram à consulta no período de estudo, 23 não se apresentaram para a coleta de sangue e 10 não quiseram participar. O modelo de regressão de Poisson foi empregado para encontrar variáveis associadas à dislipidemia. RESULTADOS: Foram incluídos 235 pacientes, dos quais 182 (77,5 por cento) tinham dislipidemia; houve prevalência maior no sexo masculino (69,8 por cento) do que no feminino (30,2 por cento); e 26,9 por cento tinham antecedentes familiares de dislipidemia contra 15,1 por cento sem este antecedente. Para o tempo de uso de TARV, tanto a média quanto a mediana foram maiores no grupo de pacientes com dislipidemia. CONCLUSÃO: Em nosso estudo, a prevalência de dislipidemia em portadores de HIV/AIDS foi alta (77,5 por cento) e foram identificados sexo masculino, história familiar de dislipidemia e tempo de uso de TARV como fatores associados.

BACKGROUND: The continuous use of antiretroviral therapy (ART) is associated with several metabolic disturbances. OBJECTIVES: The main objective of this study was to determine the prevalence of dyslipidemia in human immunodeficiency virus/acquired immunological deficiency syndrome (HIV/AIDS) patients followed in the infectious diseases outpatient clinic of Hospital Universitário Pedro Ernesto, of Universidade do Estado do Rio de Janeiro (HUPE/UERJ). MATERIAL AND METHODS: From 10/1/2004 to 5/30/2005, the participants of this study answered a survey about demographic and health data. Afterwards, the following measurements were checked: weight, height, waist and hips. Blood samples were collected for total cholesterol, high-density lipoprotein cholesterol (HDL-C) and triglycerides tests. Out of 268 patients who came to the appointment during the study period, 23 did not attend the blood collection, and 10 did not want to participate. Poisson regression model was used to find the variables associated with dyslipidemia. RESULTS: Out of the 235 patients included in the study 182 (77.5 percent) had dyslipidemia, with prevalence of male (69.8 percent) over female ones (30.2 percent). Among the patients with dyslipidemia, 26.9 percent had family history of dyslipidemia against 15.1 percent who did not. Regarding ART duration, both mean and media were higher in the group of patients with dyslipidemia. CONCLUSION: In our study the prevalence of dyslipidemia in HIV/AIDS patients was high (77.5 percent), and the associated factors were male sex, family history of dyslipidemia and ART duration.

Abscesso pulmonar causado por micobactéria do Complexo Mycobacterium avium(MAC)na Aids / Pulmonary abscess caused by the Mycobacterium avium complex (MAC) in AIDS

A micobacteriose atípica causada pelo complexo Mycobacterium avium (MAC) foi descrita como doença oportunista associada a Aids durante a década de 1980. Sua forma de apresentação, na Aids, foi sempre reconhecida como disseminada, com envolvimento do estado geral do paciente e acometimento de múltiplos órgãos, refletindo imunodeficiência grave.O quadro pulmonar isolado de MA costuma ser detectado somente entre pacientes imunocompetentes. Poucos casos de manifestações pulmonares isoladas de MA têm sido relatadas em pacientes com Aids, especialmente quando comparadas com as formas disseminadas. Relatamos o caso de um homem com Aids, acompanhado durante seis anos, com passado de retinite/colite por citomegalovírus e ressecção cirúrgica de abscesso pulmonar, cujo diagnóstico final por cultura e hibridização molecular foi infecção por M. avium.

Atypical mycobacteriosis caused by the Mycobacterium avium complex (MAC) was described as an opportunistic disease associated with AIDS during the 1980 decade. Its form of presentation among these patients was always recognized as disseminated,with involvement of general patient status as a clinical marker of severe immunodeficiency. An isolated pulmonary picture of MAC infection used to be detected only among immunocompetent patients. Few cases of isolated pulmonary manifestations of MAC infection in patients with AIDS have been reported, especially when compared to the disseminated forms. We report a case of a man followed up over a period of six years with AIDS, cytomegalovirus retinitis/colitis and asurgically resected pulmonary abscess, whose final diagnosis after culture and molecular hybridization was infection with a mycobacterium nonspecific.

Resistência aos medicamentos anti-tuberculose de cepas de Mycobacterium tuberculosis isoladas de pacientes atendidos em hospital geral de referência para tratamento de AIDS no Rio de Janeiro / Drug-resistant Mycobacterium tuberculosis strains isolated at an AIDS reference center general hospital in Rio de Janeiro

INTRODUÇAO: A tuberculose tem trazido importantes desafios ao setor de saúde. O Brasil tem alta prevalência da doença e o Estado do Rio de Janeiro possui as maiores taxas de incidência do país. O município do Rio de Janeiro é responsável pela maior notificação do estado e cerca de 30 por cento dos casos diagnosticados têm origem em hospitais. OBJETIVO: Estimar a prevalência de resistência inicial e adquirida e identificar fatores associados à ocorrência de resistência em hospital geral referência para tratamento de AIDS no Rio de Janeiro. MÉTODO: Foram analisadas cepas de Mycobacterium tuberculosis de 165 pacientes, entre agosto de 1.996 e fevereiro de 1.998. RESULTADOS: Vinte por cento (33/165) apresentaram resistência a pelo menos um medicamento: 13 por cento (22/165) à isoniazida, 1,8 por cento (3/165) à rifampicina e 3,6 por cento (6/165) a ambas. Entre pacientes infectados pelo HIV (52/165), 28,85 por cento (15/52) apresentaram resistência a pelo menos um fármaco. Resistência adquirida ocorreu em 12,5 por cento dos pacientes que referiram tratamento anterior (3/24), com associação significativa com imagem radiológica não cavitária (p = 0,05). Resistência inicial ocorreu em 18,4 por cento dos pacientes virgens de tratamento (26/141), com associação significativa com ser profissional de saúde (p = 0,004), desemprego (p = 0,03) e diarréia (p = 0,01) na análise bivariada. Na análise multivariada, ser profissional de saúde manteve-se fortemente associado com a ocorrência de resistência inicial (p = 0,002). CONCLUSAO: Taxas de resistência elevadas foram encontradas nesta série. Estes achados corroboram a necessidade de que atenção maior seja dada à tuberculose em ambiente hospitalar, em especial no que diz respeito à preocupante associação entre resistência nas cepas isoladas e profissionais de saúde.

Clinical and diagnostic aspects of intestinal microsporidiosis in HIV-infected patients with chronic diarrhea in Rio de Janeiro, Brazil

The objectives of this study were to determine both the prevalence of microsporidial intestinal infection and the clinical outcome of the disease in a cohort of 40 HIV-infected patients presenting with chronic diarrhea in Rio de Janeiro, Brazil. Each patient, after clinical evaluation, had stools and intestinal fragments examined for viral, bacterial and parasitic pathogens. Microsporidia were found in 11 patients (27.5 percent) either in stools or in duodenal or ileal biopsies. Microsporidial spores were found more frequently in stools than in biopsy fragments. Samples examined using transmission electron microscopy (n=3) or polymerase chain reaction (n=6) confirmed Enterocytozoon bieneusi as the causative agent. Microsporidia were the only potential enteric pathogens found in 5 of the 11 patients. Other pathogens were also detected in the intestinal tract of 21 patients, but diarrhea remained unexplained in 8. We concluded that microsporidial infection is frequently found in HIV infected persons in Rio de Janeiro, and it seems to be a marker of advanced stage of AIDS

Hipertensäo pulmonar primária em um paciente HIV + / Primary pulmonary hypertension in an HIV+ patient

A hipertensäo pulmonar primária (HPP) é uma doença de etiologia desconhecida, rara, caracterizada por elevaçöes na pressäo arterial pulmonar e na resistência vascular pulmonar. As lesöes vasculares variam de leve, consistindo de neoproliferaçäo da íntima, a grave, caracterizada pela fibrose concêntrica da íntima, lesöes plexiformes e arterite necrosante. Desde 1987 há relatos descrevendo a associaçäo entre o vírus da imunodeficiência humana (HIV) e HPP, chegando a cerca de 60 casos em 1997. O papel patogênico do HIV permanece desconhecido. É relatado o caso de uma mulher em que essa associaçäo foi observada.

Pericardite tuberculosa como manifestação inicial da síndrome de imunodeficiência adquirida / Tuberculous Pericarditis as the First Manifestation in Acquired Immunodeficiency Syndrome

The most common externalization of the acquired immunodeficiency syndrome (AIDS) is opportunist infection, and tuberculosis is one of the most frequent agents. The tuberculous pericarditis has been associated with AIDS, but it exceptionally occurs as the first event in the syndrome. We reported four cases in which tuberculous pericarditis was the initial manifestation of AIDS, characterizing by its clinical picture, diagnostic methods, therapeutics and the evolution of this involvement.

A forma mais comum de exteriorização da síndrome de imunodeficiência adquirida (SIDA) é a infecção oportunística, e uma das mais freqüentes em nosso meio é a tuberculose. A pericardite tuberculosa tem sido referida associada à SIDA, porém o seu encontro como manifestação inicial da doença é raro. Relatamos a ocorrência de quatro casos, em que a pericardite tuberculosa foi a primeira manifestação da SIDA, caracterizando seu quadro clínico, métodos diagnósticos, terapêutica e evolução deste tipo de envolvimento

Abscesso hepático: apresentaçäo clínica de 12 casos / Liver abscess: clinical presentation of 12 cases

Apesar dos avanços tecnológicos que permitem a sua detecçäo, os abscessos hepáticos de qualquer etiologia permanecem ainda hoje um desafio diagnóstico. Objetivou-se avaliar de maneira retrospectiva o comportamento clínico e laboratorial desta entidade nosológica durante o período de 10 anos no Serviço de DIP do Hospital Universitário Pedro Ernesto