No abstract

No abstract

Glutamate-induced excitotoxicity has been implicated as an important mechanism underlying a variety of brain injuries and neurodegenerative diseases. Previously we have shown that taurine has protective effects against glutamate-induced neuronal injury in cultured neurons. Here we propose that the primary underlying mechanism of the neuroprotective function of taurine is due to its action in preventing or reducing glutamate-induced elevation of intracellular free calcium, [Ca(2+)](i). This hypothesis is supported by the following findings. First, taurine transport inhibitors, e.g., guanidinoethyl sulfonate and beta-alanine, have no effect on taurine's neuroprotective function, suggesting that taurine protects against glutamate-induced neuronal damage through its action on the extracellular membranes. Second, glutamate-induced elevation of [Ca(2+)](i) is reduced to the basal level upon addition of taurine. Third, pretreatment of cultured neurons with taurine prevents or greatly suppresses the elevation of [Ca(2+)](i) induced by glutamate. Furthermore, taurine was found to inhibit the influx but not the efflux of (45)Ca(2+) in cultured neurons. Taurine has little effect on the binding of [(3)H]glutamate to the agonist binding site and of [(3)H]MDL 105,519 to the glycine binding site of the N-methyl-D-aspartic acid receptors, suggesting that taurine inhibits (45)Ca(2+) influx through other mechanisms, including its inhibitory effect on the reverse mode of the Na(+)/Ca(2+) exchangers (Wu et al. [2000] In: Taurine 4: taurine and excitable tissues. New York: Kluwer Academic/Plenum Publishers. p 35-44) rather than serving as an antagonist to the N-methyl-D-aspartic acid receptors.

Background HIV-infected individuals have a higher incidence of head and neck cancer. Methods Case series of 94 HIV-infected head and neck cancer patients (HIV-HNC) at six tertiary care referral centers in the US between 1991–2011. Clinical and risk factor data were abstracted from the medical record. Risk factors for survival were analyzed using Cox proportional hazard models. Human papillomavirus (HPV) and p16 testing was performed in 46 tumors. Findings were compared with SEER HNC (US-HNC) data. Results This study represents the largest HIV-HNC series reported to date. HIV-HNC cases were more likely than US-HNC to be male (91% vs. 68%), younger (median 50 vs. 62 years), non-White (49% vs.18%), and current smokers (61% vs. 18%). Median HIV-HNC survival was not appreciably lower than US-HNC survival (63 vs. 61 months). At diagnosis, most cases were currently on HAART (77%), but had detectable HIV viremia (99%) and median CD4 was 300 cells/μL (IQR=167–500). HPV was detected in 30% of HIV-HNC and 64% of HIV-oropharyngeal cases. Median survival was significantly lower among those with CD4 counts ≤200 than >200 cells/μL at diagnosis (16.1 vs. 72.8 months, p<0.001). In multivariate analysis, poorer survival was associated with CD4 <100 cells/μL (aHR=3.09, 95%CI=1.15–8.30), larynx/hypopharynx site (aHR=3.54, 95%CI=1.34–9.35), and current tobacco use (aHR=2.54, 95%CI=0.96–6.76). Conclusion Risk factors for the development of HNC in patients with HIV infection are similar to the general population, including both HPV-related and tobacco/alcohol-related HNC.

BackgroundRapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population.MethodsThe Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit.ResultsThere were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models.ConclusionsThis is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.

Supplemental Digital Content is available in the text

Background The number of HIV-infected women giving birth in the U.S. is increasing. Research on pregnancy planning in HIV-infected women is limited. Methods Between January 1 and December 30, 2012, pregnant women with a known HIV diagnosis prior to conception at 12 U.S. urban medical centers completed a survey including the London Measure of Unplanned Pregnancy (LMUP) scale. We assessed predictors of LMUP category (unplanned/ambivalent versus planned pregnancy) using bivariate and multivariable analyses. Results Overall, 172 women met inclusion criteria and completed a survey. Based on self-report using the LMUP scale, 23% of women had an unplanned pregnancy, 58% were ambivalent and 19% reported a planned pregnancy. Women were at lower risk for an unplanned or ambivalent pregnancy if they had previously given birth since their HIV diagnosis (adjusted Relative Risk = 0.67, 95% CI 0.47-0.94, p=0.02), had seen a medical provider in the year before the index pregnancy (aRR 0.60, 95% CI 0.46-0.77, p<0.01), or had a patient-initiated discussion of pregnancy intentions in the year prior to the index pregnancy (aRR = 0.63, 95% CI 0.46-0.77, p<0.01). Unplanned or ambivalent pregnancy was not associated with age, race/ethnicity, or educational level. Conclusions In this multi-site U.S. cohort, patient-initiated pregnancy counseling as well as being engaged in medical care prior to pregnancy were associated with a decreased probability of unplanned or ambivalent pregnancy. Interventions that promote health-care engagement among HIV-infected women and integrate contraception and preconception counseling into routine HIV care may decrease the risk of unplanned pregnancy among HIV-infected women in the U.S.

SUMMARY SETTING-Multidrug-resistant tuberculosis (MDR-TB) treatment facility, Orel Oblast, Russian Federation.OBJECTIVES-To determine factors associated with poor outcome and to document status of patients after recording of TB outcomes. DESIGN-Retrospective review of prospective single cohort.RESULTS-Among 192 patients, factors significantly associated with poor outcome in multivariate analysis include three or more treatment interruptions during the intensive phase of therapy and alcohol or drug addiction (adjusted OR [aOR] 2.1, 95%CI 1.0-4.3 and aOR 1.9, 95%CI 1.0-3.7). Previous treatment was associated with poor outcome, but only among smearpositive patients (aOR 3.1,3). Ten patients (5%) developed extensively drugresistant TB (XDR-TB) during treatment; of 115 patients with at least 6 months of follow-up data after outcomes were recorded, 13 (11%) developed XDR-TB.CONCLUSION-Interventions focused on supporting patient adherence during the intensive phase of treatment; the management of drug and alcohol addiction should be developed and studied. A substantial proportion of patients developed XDR-TB during and after treatment. Longer term follow-up data of patients treated for MDR-TB are needed to better inform programmatic policy. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptTreatment outcomes for multidrug-resistant tuberculosis (MDR-TB), defined as TB caused by Mycobacterium tuberculosis strains resistant to both isoniazid (INH) and rifampin (RMP), are significantly worse than for drug-susceptible TB, but have varied widely. [1][2][3][4] Moreover, patients documented as having a good outcome do not always do well over time. [5][6][7][8] However, few reports have documented longer term follow-up of patients uniformly treated with second-line agents. Extensively drug-resistant TB (XDR-TB), defined as MDR-TB that is additionally resistant to a fluoroquinolone and an injectable second-line drug (SLD), is even more difficult to treat than MDR-TB; 9-13 however, relatively little has been documented about the risks of developing XDR-TB during and after the treatment of MDR-TB. 14 Political change and economic difficulties in Russia in the 1990s contributed to difficulties obtaining medications, which increased the incidence of MDR-TB. 15 By 2000, the prevalence of MDR-TB among newly treated patients in some oblasts exceeded 9%. 16 Treatment success, and risk factors associated with outcome, among patients in MDR-TB treatment programs in countries of the former Soviet Union have varied. 4,9,17,18 A better appreciation of these differences in treatment outcome may help elucidate reasons for treatment success or failure, and guide programmatic policy.The Orel Oblast DOTS-Plus Tuberculosis Treatment Project was one of the first Green Light Committee (GLC) approved programs in the Russian Federation specifically designed to treat MDR-TB with individualized regimens. The first cohort began enrollment in 2002, and the program has been active since.The purpose of this analysis...