Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55-5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed

Increased Risk of Barrett's Esophagus Among Individuals Born Preterm or Small for Gestational Age

Background &amp; AimsGastroesophageal reflux is common in infants during their first year of life, especially in those born preterm or small for gestational age (SGA). We assessed whether being born preterm or SGA increased the risk of developing Barrett's esophagus (BE) in adulthood.MethodsWe performed a population-based case-control study of patients with BE (cases) that were diagnosed at 2 Swedish hospitals from January 1, 1986, through December 31, 2005. We identified the birth hospital of the cases; data on perinatal characteristics such as gestational age at birth and birth weight were collected from original birth records. We also obtained and collected information on the 3 singleton live births, of the same sex, born after each case at the same maternity ward (controls). In total, we analyzed data from 331 cases and 852 matched controls. We used conditional logistic regression to determine odds ratios (ORs), determined 95% confidence intervals (CIs), and adjusted for potential confounding factors.ResultsCompared with infants born with a normal birth weight (3000–3999 g), infants with low birth weight (&lt;2500 g) were at increased risk of BE (adjusted OR, 8.22; 95% CI, 2.83–23.88). This was mainly due to an effect of SGA rather than preterm birth. Specifically, compared with infants with normal birth weight for gestational age (25th–75th percentiles), the odds of BE among very SGA infants (&lt;3rd percentile) was nearly tripled (adjusted OR, 2.95; 95% CI, 1.35–6.44).ConclusionsOn the basis of a population-based study of patients with BE in Sweden, infants born SGA have a 3-fold increase in risk for developing BE as adults, compared with infants of normal birth weight for gestational age

B-oligomer of pertussis toxin inhibits HIV-1 LTR-driven transcription through suppression of NF-kappaB p65 subunit activity.

The binding subunit of pertussis toxin (PTX-B) has been shown recently to inhibit the entry and postentry events in HIV-1 replication in primary T lymphocytes and monocyte-derived macrophages. While the effect of PTX-B on HIV-1 entry was shown to involve CCR5 desensitization, the mechanism of postentry inhibition remained unclear. In T lymphocytes, PTX-B affected transcription or stability of Tat-stimulated HIV-1 mRNAs. In this study, we sought to identify the mechanism of postentry inhibition of HIV-1 replication by PTX-B in U-937 promonocytic cells. We demonstrate that in these cells PTX-B inhibits expression of luciferase reporter gene controlled by the HIV-1 LTR promoter. This effect is Tat-independent and is not restricted to the HIV-1 LTR promoter. Instead, PTX-B activity is mediated through suppression of the cellular transcription factor, NF-kappaB. PTX-B inhibits phosphorylation and nuclear translocation of the p65 subunit of NF-kappaB. This effect is independent of the cytoplasmic NF-kappaB inhibitor, IkappaBalpha, as PTX-B stimulates phosphorylation and subsequent degradation of this protein. The suppressive activity of PTX-B on NF-kappaB p65 phosphorylation and nuclear translocation is delayed, suggesting that PTX-B signaling might initiate synthesis and cytoplasmic accumulation of a p65 phosphorylation inhibitor.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe