Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population.

Esophageal cancer is among the most common and fatal tumors in the world. Eighty percent of esophageal tumors are esophageal squamous cell carcinoma (ESCC). Brazil is one of the high incidence areas in the West, where tobacco and alcohol consumption have been associated with ESCC. However, polymorphisms in xenobiotic metabolizing genes may also contribute to the risk. Therefore, in this study, we analyzed the risk of ESCC associated with tobacco and alcohol consumption and with polymorphisms of CYP2A6 (CYP2A6*2), CYP2E1 (CYP2E1*5B, CYP2E1*6), GSTP1 (Ile105Val), GSTM1 and GSTT1 null genotypes in 126 cases and 252 age- and gender-matched controls. Data on the amount, length and type of tobacco and alcohol consumed were collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analyzed by polymerase chain reaction (PCR)-multiplex (GSTM1 and T1), PCR-Restriction Fragment Length Polymorphism (CYP2E1*5B and *6 and GSTP1 Ile105Val) or allele-specific PCR amplification (CYP2A6*2). Risks were evaluated by multivariate conditional regression analysis. As expected, tobacco [odds ratio (OR) = 6.71, 95% confidence interval (95% CI) 3.08-14.63] and alcohol (OR = 16.98, CI 7.8-36.98) consumption, independently or together (OR = 26.91, CI 13.39-54.05) were risk factors. GSTP1 Ile105Val polymorphism was an independent risk factor (OR = 2.12, CI 1.37-3.29), whereas GSTT1 wild-type was an independent protective factor for ESCC (OR = 0.37, CI 0.16-0.79). There was approximately 80% statistical power to detect both results. There was no risk associated with CYP2A6, CYP2E1 and GSTM1 polymorphisms. In conclusion, this study suggests an opposite role of GSTP1 and GSTT1 polymorphisms for the risk for ESCC.

Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy.

Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

Acute-phase proteins among patients with type 1 diabetes.

OBJECTIVE: To determine whether young type 1 diabetic patients without clinical microvascular or macrovascular complications have altered levels of acute-phase proteins (AFP), alpha(1)-acid glycoprotein (AGP), C-reactive protein (CRP) and fibrinogen and whether their AFP levels are related to glycemic control. RESEARCH DESIGN AND METHODS: We studied cross-sectionally 48 type 1 diabetic outpatients (25 males) aged 19.9 +/- 9.8 years with a duration of diabetes of 5 (1-21) years, without clinical chronic complications and 66 non-diabetic subjects (26 males) aged 23.1 +/- 10.9 years. Inclusion criteria were normoalbuminuria, normal eye fundoscopy, and no evidence of cardiovascular disease or neuropathy. RESULTS: High CRP [0.23 (0.01-2.90 l) vs (0.14 (0.01-2.41l) mg/dl p=0.01] and AGP [53.5(40-78) vs 40.0(40-115) mg/dl p=0.0001] levels were found in patients with type 1 diabetes compared to nondiabetic subjects. In the pooled group studied, AGP was correlated with CRP, HbA(1c), fasting plasma glucose (FBG) and AER and CRP was correlated with HbA(1c) and AER. The correlation of AGP and CRP with AER persisted after controlling for HbA(1c) and FBG. Stepwise multiple regression with AGP as the dependent variable showed that FBG and HbA(1c) were the significant independent variables. No correlation between AFP and HBA(1c) and FBG was observed in the diabetic group. CONCLUSIONS: According to our results, AFP, a known marker of low-grade chronic inflammation, are increased in patients with type 1 diabetes probably independently of glycemic control and the presence of clinical microvascular or macrovascular disease. The influence of AFP on the development of chronic complications in patients with type 1 diabetes must be addressed in prospective studies.

Reactional states in multibacillary Hansen disease patients during multidrug therapy.

It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI < 3, while ENL predominated among those patients with BI > 3.

[Anthropometric profile of children aged 0 to 5 years in the city of Niterói, Rio de Janeiro, Brazil]. / Perfil antropométrico de crian as de 0 a 5 anos do Município de Niterói, Rio de Janeiro, Brasil.

The Niterói-based Nutritional and Food Surveillance System (SISVAN Niteroi, RJ, Brazil) performed an anthropometric survey which included 2,248 children from zero to 60 months of age in September 1992, during a mass vaccination day program. The purpose was to determine the nutritional status of children from that city. The indexes used were Weight for Age (WA), Weight for Height (WH), and Height for Age (HA), and the reference population was that of the NCHS (National Center for Health Statistics, USA), adopted and recommended by the WHO. The indexes were analyzed using the classifications by Gomez and Z-Scores. Prevalence of undernutrition was calculated on the basis of the proportion of children with Z-scores under -2.00, using HAZ to stabilish chronic forms and WHZ for acute ones. A data base was built using Epi Info, version 5.0 1b, and a special program from CDC (Centers for Disease Control) was used to calculate anthropometric indexes. The results showed as much as 20.1 % of undernutrition, including all forms from the Gomez classification. In the city as a whole, 6.8% had HAZ under -2.00. The results indicated a serious situation of chronic undernutrition that demands continuous nutritional surveillance in Niteroi, and especially in the city's Eastern District.

[Leprosy epidemiology in a cohort of household contacts in Rio de Janeiro (1987-1991)]. / Epidemiologia da hanseníase em coorte de contatos intradomiciliares no Rio de Janeiro (1987-1991).

This study aimed to identify factors influencing the development of leprosy (Hansen's disease) in household contacts. A dynamic cohort was analyzed from 1987 to 1991 at the Hansen's Disease Department of the Oswaldo Cruz Foundation in Rio de Janeiro. The incidence rate was 0.01694 person-years of follow-up. Nevertheless, for subjects at the end of the first year of follow-up the incidence rate was 0.06385 (end of second year, 0.03299; end of third year, 0.02370; end of fourth year, 0.018622; and end of observation period, 0.01694). A stepwise multivariate logistic regression model was proposed to study the risk of developing leprosy, including co-prevalent cases, totaling 758 contacts. In the final model, the risk was associated with a negative Mitsuda skin test (OR = 3.093; CI 95% = 1.735-5.514), prior BCG vaccination (OR = 0.3802; CI 95% = 0.2151-0.66719), and multibacillary primary clinical form (OR = 2.547; CI 95% = 1.249-5.192). The results showed that both multibacillary leprosy and specific immune status are significant indicators for developing the disease in a cohort of household contacts.

Factors associated with viral load suppression in HIV-infected pregnant women in Rio de Janeiro, Brazil.

Viral load (VL) near delivery is a determinant of mother-to-child transmission (MTCT) of HIV. To evaluate factors associated with an undetectable VL near delivery in HIV-infected pregnant women receiving highly active antiretroviral therapy (HAART) and non-HAART regimens, HIV-infected pregnant women with a detectable VL at entry and having used antiretrovirals for ≥4 weeks before delivery were selected. Multivariate analysis was employed using binary logistic unconditional models; the dependent variable was having a VL <400 copies/mL near delivery. VL suppression was achieved in 403/707 women (57%): 65.4% in the HAART group, but only 26% in the non-HAART group P = 0.001. Duration of HAART was correlated with VL suppression, with maximum benefit seen after ≥12 weeks of therapy (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.72-3.65). CD4+ cell count near delivery (OR: 1.53; 95% CI: 1.06-2.20) and baseline VL (OR: 0.74; 95% CI: 0.58-0.94) were also independently associated with VL suppression. Overall MTCT rate was 1.6%. HAART for ≥12 weeks, baseline VL and CD4 cell count near delivery were independently associated with viral suppression near delivery.

Drug-resistant tuberculosis in six hospitals in Rio de Janeiro, Brazil.

SETTING: Tuberculosis (TB) drug resistance survey in six hospitals in Rio de Janeiro, Brazil. OBJECTIVE: To estimate resistance to at least one drug (DR) and multidrug resistance (MDR) and identify associated factors. DESIGN: One-year cross-sectional survey. Hospitals were included as a convenience sample. RESULTS: Of 595 patients investigated, 156 (26.2%) had previously undergone anti-tuberculosis treatment, 433 (72.8%) were not previously treated and information on the remaining 6 was not available. Overall, DR and MDR rates were high, at respectively 102 (17.1%, 95%CI 14.3-20.5) and 44 (7.4%, 95%CI 5.5-9.9) cases. Among individuals not previously treated, 17 had MDR (3.9%, 95%CI 2.4-6.3) and diagnosis in a TB reference hospital was independently associated with MDR (prevalence ratio [PR] 3.3, 95%CI 1.2-8.7) after multivariate analysis. Among previously treated individuals, 27 had MDR (17.3%, 95%CI 11.7-24.2). MDR-TB was independently associated with diagnosis in a TB reference hospital (PR 3.6, 95%CI 1.5-8.7), male sex (PR 2.3, 95%CI 1.2-4.4) and dyspnoea (PR 0.3, 95%CI 0.1-0.7). CONCLUSION: We found high levels of DR- and MDR-TB. Our study design did not permit us to determine the contribution of community versus nosocomial transmission. Further studies are needed to establish this. Nevertheless, hospitals should be recognised as a potential source of transmission of resistant TB strains and urgent measures to avoid nosocomial TB transmission should be taken.

Use of ML dipstick as a tool to classify leprosy patients.

Leprosy control services face the problem of leprosy patients being misclassified by the lack of or the poor quality of skinsmear examination services. Misclassification increases the risk of relapse due to insufficient treatment if a multibacillary (MB) patient is classified as paucibacillary (PB), thereby also prolonging the time that the patient is infectious. The World Health Organization (WHO) recommends at present an alternative classification based on the number of skin lesions. Its reliability, however, has been questioned. Our investigation sought to determine the usefulness of the ML Dipstick, a simple field assay to detect IgM antibodies to phenolic glycolipid-I of Mycobacterium leprae, for the classification of leprosy patients in addition to lesion count. In this study, 264 leprosy patients were investigated. Of 130 patients with a positive bacterial index (BI), 19 (14.6%) had less than 6 lesions and would have been classified as PB. Out of 134 patients with a negative BI, 26 (19.4%) had 6 or more lesions and would have been classified as MB patients if the lesion counting system would apply. Thus, the classification based on the number of lesions only was found to be 85% sensitive and 81% specific (using the BI as the gold standard) at detecting MB cases among the studied population. Sensitivity would have increased if patients would have been classified according to a combination of the number of lesions and the dipstick result. In that case patients are classified as MB when they are either dipstick positive (N = 16), have more than 6 lesions (N = 43), or both (N = 94). Patients negative for both dipstick and number of lesions would have been classified as PB (N = 111). The classification based on the number of lesions alone left 19 BI-positive cases classified as PB, while the combination method of the ML Dipstick and number of lesions left only 8 BI-positive cases classified as PB (5 borderline, 2 borderline lepromatous and 1 tuberculoid), thus preventing undertreatment. The combination method of the ML Dipstick and lesion counting was found to be 94% sensitive and 77% specific, which is an improvement of 9% (chi-squared test, p = 0.025) in sensitivity compared to lesion counting only. The results of this study indicate that testing all patients initially classified by lesion counting as PB (48% in our study population) with the dipstick can significantly contribute to improved classification of leprosy patients for treatment purposes.

Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5 percent of the patients.

Migracao leucocitaria "in vivo" em pacientes submetidos a dialise peritoneal periodica. / \"In vivo leucocyte migration in patients under chronic peritoneal dialysis

Analisou-se o conteudo celular dialitica drenada da cavidade peritoneal, durante dialise peritoneal, em cinco pacientes com insuficiencia renal cronica. As celulas obtidas mostraram sempre viabilidade maior que 90%, e foram analisadas pelo metodo de Giemsa e metodos citoquimicos para esterase acida e mieloperoxidase. No inicio do procedimento dialitico, observou-se um pico celular composto basicamente por fagocitos mononucleares, linfocitos e eosinofilos. Em tres dos cincos pacientes, apos grande reducao do numero de celulas drenadas da cavidade peritoneal, observou-se um segundo pico celular composto principalmente por neutrofilos, com desaparecimento de outros tipos celulares. Este segundo pico celular nao foi observado em outros dois pacientes, o que sugere a existencia de diferentes padroes de migracao leucocitaria para cavidade peritoneal