Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to <it>Mycobacterium tuberculosis</it>: a pilot study

Abstract Rationale Existing data on the effect of treatment of latent tuberculosis infection (LTBI) on T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens are contradictory. Differences in technical aspects of the assays used to detect this response and populations studied might explain some of these discrepancies. In an attempt to find surrogate markers of the effect of LTBI treatment, it would be important to determine whether, among contacts of patients with contagious tuberculosis, therapy for LTBI could cause changes in MTB-specific immune responses to a variety of RD1-antigens. Methods and results In a longitudinal study, 44 tuberculin skin test+ recent contacts were followed over a 6-month period and divided according to previous exposure to MTB and LTBI treatment. The following tests which evaluate IFN-gamma responses to RD1 antigens were performed: QuantiFERON TB Gold, RD1 intact protein- and selected peptide-based assays. Among the 24 contacts without previous exposure that completed therapy, we showed a significant decrease of IFN-gamma response in all tests employed. The response to RD1 selected peptides was found to be more markedly decreased compared to that to other RD1 antigens. Conversely, no significant changes in the response to RD1 reagents were found in 9 treated subjects with a known previous exposure to MTB and in 11 untreated controls. Conclusion These data suggest that the effect of INH prophylaxis on RD1-specific T-cell responses may be different based on the population of subjects enrolled (recent infection versus re-infection) and, to a minor extent, on the reagents used.</p

Coastal structure, sea-level changes and vertical motion of the land in the Mediterranean

<p>The Mediterranean basin is an important area of the Earth for studying the interplay between geodynamic processes and landscape evolution affected by tectonic, glacio-hydro-isostatic and eustatic factors. We focus on determining vertical deformations and relative sea-level change of the coastal zone utilizing geological, archaeological, historical and instrumental data, and modelling. For deformation determinations on recent decadal to centennial time scales, seismic strain analysis based on about 6000 focal mechanisms, surface deformation analysis based on some 850 continuous GPS stations, and 57 tide gauge records were used. Utilizing data from tectonically stable areas, reference surfaces were established to separate tectonic and climate (eustatic) signals throughout the basin for the last 20 000 years. Predominant Holocene subsidence (west coast of Italy, northern Adriatic sea, most of Greece and Turkey are areas at risk of flooding owing to relative sea-level rise), uplift (local areas in southwestern Italy and southern Greece) or stability (northwestern and central western Mediterranean and Levant area) were determined. Superimposed on the long trends, the coasts are also impacted by sudden extreme events such as recurring large storms and numerous, but unpredictable tsunamis caused by the high seismicity of parts of the basins. </p

Application of a Molecular Panel To Demonstrate Enterotropic Virus Shedding by Healthy and Human Immunodeficiency Virus-Infected Patients

We used a molecular panel, targeting seven enteric viruses, to explore the advantage of using molecular methods to establish the etiology of enteric diseases and to evaluate the prevalence of enteric viruses in asymptomatic human immunodeficiency virus-infected patients. This approach favors rapidity and sensitivity of laboratory diagnosis of viral enteric syndromes

Plasma lipid profile in pregnant women with HIV receiving nevirapine

Limited information is currently available on the metabolic profile of nevirapine in pregnancy. We used data from a national observational study to evaluate plasma lipid profile in pregnant women receiving nevirapine. Lipid values were collected during routine clinical visits. Midpregnancy (second trimester) lipid values were analyzed according to use of nevirapine, calculating differences and 95% confidence intervals (CI) between women taking and not taking this drug. In order to adjust for possible confounders, multivariable models were constructed using as dependent variables levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight, previous treatment history, CD4 count, and presence of any antiretroviral therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the time of blood sampling. Overall, 375 women had available data for analysis. Pregnant women on nevirapine, compared to women not taking this drug, had in univariate analyses higher levels of HDL-C (difference: +13.0mg/dL [95%CI 7.4-18.6], p<0.001), lower values of TC/HDL-C ratio (difference: -0.51 [0.23-0.80], p<0.001) and a trend for lower levels of triglycerides (difference: -17.6mg/dL [0.7-35.9], p=0.06). Higher HDL-C levels were also associated with use of protease inhibitors and with no previous antiretroviral experience before pregnancy. The associations with higher HDL-C levels were confirmed in multivariable analyses. Our study indicates in pregnant women an association between nevirapine use and higher HDL-C levels. Further studies should assess whether this effect is due to an intrinsic activity of nevirapine and define the potential mechanisms involved. © Copyright 2009, Mary Ann Liebert, Inc

Factors Influencing Gestational Age-Adjusted Birthweight in a National Series of 600 Newborns from Mothers with HIV

Background: Few studies have assessed the determinants of birthweight in newborns from HIV-positive mothers in analyses that adjusted for different gestational age at delivery. Method: We calculated gestational age-adjusted birthweightZ-score values in a national series of 600 newborns from women with HIV and in 600 newborns from HIV-negative women matched for gender and gestational age. The determinants of Z-score values in newborns from HIV-positive mothers were assessed in univariate and multivariate regression analyses. Results: Compared to newborns from HIV-negative women, newborns from HIV-positive women had significantly lower absolute birthweight (2799 vs. 2887 g;p=.007) and birthweightZscore (-0.430 vs. -0.222; p 10 cigarettes/day (ZSD 0.323, 95% CI 0.129-0.518, p=.001), absence of pregnancies in the past (ZSD 0.200, 95% CI 0.050-0.349, p=.009), no antiretroviral treatment in the past (ZSD 0.186, 95% CI 0.044-0.327, p=.010), and Caucasian ethnicity compared to Hispanic (ZSD 0.248, 95% CI 0.022-0.475, p=.032). Body mass index (BMI) at conception and maternal glycemia levels during pregnancy were also significantly related to birthweight Z scores. Glycemia, BMI, and recent substance use maintained a significant association with Z-score values in multivariate analyses. In the multivariate analysis, the only factors significantly associated with Z-score values below the 10th percentile were recent substance use (adjusted odds ratio [AOR] 3.17, 95% CI 1.15-8.74) and smoking (AOR 2.26, 95% CI 1.13-4.49). Discussion: We identified several factors associated with gestational age-adjusted birthweight in newborns from women with HIV Smoking and substance use have a significant negative impact on intrauterine growth, which adds to an independent HIV-related effect on birthweight. Prevention and information on this issue should be reinforced in women with HIV of childbearing age to reduce the risk of negative outcomes in their offspring

Lipodystrophy is an independent predictor of hypertriglyceridemia durino pregnancy in HIV- infected women

Lipid values were measured during pregnancy in HIV-infected, treatment-experienced women. A previous history of lipodystrophy was associated with significantly higher triglyceride values at all pregnancy trimesters. In multivariate analyses lipodystrophy independently increased the risk of hypertriglyceridemia by threefold at the first trimester, and by eightfold at the second and third trimesters. Protease inhibitor treatment was also independently associated with hypertriglyceridemi