Macrodetermined racial inequalities in diagnostic testing among tuberculosis patients in Brazil.

OBJECTIVES: To estimate the association between tuberculosis (TB) patients' race and patients' access to diagnostic testing in Brazil. In addition, we evaluated if the associations could be explained by a geographic codistribution between racial groups and diagnostic testing. STUDY DESIGN: It is a cross-sectional study based on secondary data from a national surveillance system of new TB cases diagnosed in 2015. METHODS: We evaluated the association between TB patients' race (independent variable) and the HIV testing and TB mycobacterial culture providing (dependent variables) with logistic regression models. We used multilevel models to consider different geopolitical levels (region, state and municipality). In addition, we used conditional logistic regressions matched by health-care unit. All models were adjusted by individual covariates associated with the outcomes. RESULTS: Compared with non-Afro-Brazilian patients, Afro-Brazilian patients had significantly lower odds to have had HIV testing [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.69-0.75] and mycobacterial culture performed (OR: 0.74; 95% CI: 0.71-0.77). However, these statistically significant negative associations between Afro-Brazilian racial category and testing disappeared when patients were considered as nested in geopolitical contexts or matched for health-care unit. CONCLUSIONS: Afro-Brazilian TB patients had lower probability to have HIV test and mycobacterial culture performed. However, these associations seem to be macrodeterminated by the geographic distribution of both racial groups and diagnostic testing. Our findings can support the formulation of public policies aiming to mitigate regional disparities as a strategy to improve racial equity in access to healthcare. The approach presented can be applied in a range of scenarios to identify disparities, localize its source and support decision-making.

Factors associated with the drug-resistant tuberculosis incidence rate in Brazil.

SETTING: The selection and transmission of drug-resistant strains of tuberculosis (TB) hamper disease control. OBJECTIVE: To identify health conditions, demographic and socio-economic factors, as well as individual factors associated with the incidence of drug-resistant TB (DR-TB), in Brazil at the municipal level. DESIGN: This was an ecological study covering Brazilian municipalities that had reported DR-TB cases in 2014. Associations were evaluated in a multilevel analysis using negative binomial regression. RESULTS: In the multilevel model, males (incidence rate ratio [IRR] 2.6, 95% confidence interval [CI] 2.3-2.93) and Black persons (IRR 1.82, 95%CI 1.61-2.05) had a higher risk of DR-TB. Compared with those aged 60 years, persons aged 15-59 years (IRR 1.72, 95%CI 1.40-2.11) also had a higher risk. The following contextual factors were associated with the incidence rate (IR) of DR-TB: proportion of previously treated patients (IRR 1.27, 95%CI 1.1-1.5), acquired immune-deficiency syndrome IR (IRR 1.13, 95%CI 1.02-1.25), Municipal Human Development Index (IRR 0.72, 95%CI 0.64-0.81) and the Gini coefficient (IRR 0.86, 95%CI 0.78-0.95). CONCLUSION: We have identified individual and contextual factors associated with the incidence of DR-TB. Our results may help improve integrated public health interventions aimed at controlling DR-TB in Brazil.

Interleukin-4 increases the permeability of human endothelial cells in culture.

BACKGROUND: IL-4 plays a key role in the induction of allergic inflammation, but its role as an effector molecule is less well-established. Although some observations suggest that IL-4 may mediate increased vascular permeability, which is a characteristic feature of allergic inflammation, evidence for a direct effect on endothelial cell permeability is lacking. OBJECTIVE: To determine the effect of human IL-4 on the albumin permeability of cultured human endothelial cells. METHODS: Human umbilical vein endothelial cells were cultured on permeable membranes and the albumin permeability of endothelial monolayers was measured with and without exposure to recombinant human IL-4. Endothelial cells were exposed to various concentrations of IL-4 (0.001-100 U/mL), for various durations (6-24 h), either in the presence or absence of anti-IL-4 antibody. Recovery of endothelial barrier function following exposure to IL-4 was also examined. RESULTS: IL-4 induced a dose-dependent, reversible increase in endothelial permeability to albumin. Low concentrations of IL-4 (1 U/mL) induced a significant increase in endothelial permeability (P=0.004). IL-4-mediated endothelial leak occurred rapidly, within 6 h of exposure. CONCLUSIONS: IL-4 has the capacity to induce vascular leak by a direct effect on cultured endothelial cells, suggesting a potential effector role for IL-4 in the pathogenesis of vascular leak in allergic diseases.

Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction.

Dengue virus nonstructural protein 1 (NS1) is expressed on the surface of infected cells and is a target of human antibody responses to dengue virus infection. We show here that dengue virus uses the cellular glycosyl-phosphatidylinositol (GPI) linkage pathway to express a GPI-anchored form of NS1 and that GPI anchoring imparts a capacity for signal transduction in response to binding of NS1-specific antibody. This study is the first to identify GPI linkage of a virus-encoded protein. The GPI anchor addition signal for NS1 was identified, by transfection of HeLa cells with dengue cDNA constructs, as a downstream hydrophobic domain in NS2A. GPI linkage of NS1 in both transfected and infected cells was demonstrated by cleavage of NS1 from the surface by PI-specific phospholipase C and by metabolic incorporation of the GPI-specific components ethanolamine and inositol. In common with other GPI-anchored proteins, addition of specific antibody resulted in signal transduction, as evidenced by tyrosine phosphorylation of cellular proteins. Antibody-induced signal transduction by GPI-linked NS1 suggests a mechanism of cellular activation that may contribute to the pathogenesis of human dengue disease. Signal transduction by a GPI-anchored viral antigen interacting with a specific antibody that it induces is a new concept in the pathogenesis of viral disease.

Prevalence of cytomegalovirus in the gastrointestinal tract of renal transplant recipients with persistent abdominal pain.

Abdominal pain occurs frequently in renal transplant recipients receiving mycophenolate mofetil (MMF) therapy. The cause of this abdominal pain has not been fully elucidated, but may involve local irritation, as well as inhibition of rapidly dividing cells of the gastrointestinal (GI) tract. This milieu of inflammation and added immunosuppression is conducive to activation of cytomegalovirus (CMV). We therefore sought to find the prevalence of active CMV in patients presenting with abdominal pain on maintenance MMF therapy. All patients receiving a renal transplant at our center from March 1, 1997, to September 1, 1997, were studied. Any patient presenting with midepigastric pain for greater than 3 days underwent esophagogastroduodenoscopy (EGD) with biopsy. CMV was diagnosed by the presence of inclusion bodies and immunohistochemical studies. Ten patients presented with persistent midepigastric pain; nine of these patients had evidence of GI CMV. Patients who were CMV negative and received an allograft from CMV-positive donors and those with leukopenia were at significantly increased risk for the development of abdominal pain. In our study population, the majority of patients on maintenance MMF therapy who presented with persistent midepigastric pain had evidence of active CMV infection in the upper gastrointestinal tract.

Dengue: a continuing challenge for molecular biology.

Ten years ago Scott Halstead published a seminal review outlining the challenge to science provided by dengue. Our review summarizes recent efforts to meet this challenge and discusses the potential practical implications of basic research. One major long-term goal is the development of a vaccine, and several different strategies are currently being advanced. Clinical studies on dengue continue to help physicians make rational choices in disease management.

Evaluation of voiding cystourethrography prior to renal transplantation.

In many centers, voiding cystourethrography is a routine part of pretransplantation assessment of the lower urinary tract. To assess the value of this investigation, a retrospective review of transplant candidates evaluated in our center over 2 years was undertaken. A total of 517 patients were fully evaluable. Only 13 voiding cystourethrograms (VCUGs) (2.5%) of 517 were found to be abnormal. Three patients with reflux alone did not require intervention before transplantation. Four patients with decreased bladder capacity underwent hydrodistention. Two patients increased their capacity to over 150 ml and two patients failed distention, one requiring an ileal conduit and the other requiring an augmentation cystoplasty. Three patients had increased postvoid residual (PVR). Two patients started clean intermittent catheterization. One required prostate resection for benign prostatic hypertrophy. One patient with reflux and decreased bladder capacity refused treatment. One patient with reflux combined with increased PVR started clean intermittent catheterization and was cleared for transplant surgery. One patient with decreased bladder capacity and increased PVR had a stroke and was excluded from transplantation. All 13 patients with abnormal VCUGs had a prior urologic history. In total, only 56 of 517 patients evaluated had a prior urological history. Each VCUG costs approximately $500. Limiting VCUG studies to those patients with a prior urological history would have resulted in a significant cost savings. Hence, we recommend that only patients with a prior urological history should undergo this costly and often distressing examination.

Friendships, femininity, and reaction to affective arousal.

This study examined relations between college women's scores on femininity and their same-sex friendships and how these women's perceptions were influenced by induction of success or failure. 200 undergraduate women described themselves and their best friends on the dominance and submissiveness scales of the Interpersonal Adjective Scales and also completed the Behavioral Self-report of Femininity and a biographical information sheet. Mean ratings of dominance were above average both for self and best-friend ratings, but these two dominance ratings were not significantly correlated. However, women viewed themselves as similar to their best friends on submissiveness characteristics. Highly feminine women described themselves as more dominant than less feminine women. Highly feminine women also experienced less anxiety and fatigue as measured by the Profile of Mood States in response to failure induction than less feminine women. Both sets of results are contrary to expectations, but the behavioral definition of femininity was different from that used earlier.

Laparoscopic internal drainage of lymphocele in renal transplant.

Lymphoceles frequently develop following renal transplant surgery. The conventional methods used to drain lymphoceles are invasive and can be associated with complications. Laparoscopic drainage of posttransplant lymphoceles provides a safer alternative.

Mitomycin-induced hemolytic-uremic syndrome. Successful treatment with corticosteroids and intense plasma exchange.

Mitomycin has been associated with microangiopathic hemolytic anemia and renal failure. We describe a patient with the adult hemolytic-uremic syndrome due to mitomycin who was successfully treated with intense plasma exchange therapy and corticosteroid therapy. Patients receiving mitomycin should have their conditions monitored closely for acute renal failure, thrombocytopenia, and hemolytic anemia.

Control of hepatitis B infection. The role of surveillance and an isolation hemodialysis center.

A 3 1/4-year study assessed intervention approaches for hemodialysis-associated hepatitis. A 12-month retrospective study was followed by one year of prospective surveillance (during which attention to hygienic techniques was encouraged) and then by a 15-month period during which antigen-positive cases were transferred from study centers to an isolation hemodialysis center (IHL). The incidence of hepatitis B infection (HBI) fell 35.9% in study centers during surveillance; this was followed by a 50.0% drop during the IHC phase. The total 67.9% drop during the entire study period was statistically highly significant; the IHC contributed significantly more to the total drop than did surveillance alone. At comparison units, HBI increased 97.9% during the same period. This study indicates that HBI incidence can be markedly reduced by a combination of surveillance and assignment of antigen-positive patients to a separate dialysis unit.

Cisplatin-induced hypocalcemia and hypomagnesemia.

Cisplatin (cis-diamminedichloroplatinum), a chemotherapeutic agent active against solid tumors, is a known cause of acute renal failure and renal tubular dysfunction. We saw a case of renal magnesium wasting and hypomagnesemia in a 58-year-old woman with genital pelvic malignancy. Her initial manifestation was that of chronic symptomatic hypocalcemia of four months' duration. The relatively reduced parathyroid hormone level in this patient and the possible sites of cisplatin-induced renal tubular dysfunction resulting in hypermagnesuria were evaluated. This case emphasizes the importance of serially observing cisplatin-treated patients for the possible development of hypomagnesemic hypocalcemia.