Sexual Risk Intervention In Multiethnic Drug And Alcohol Users

An estimated 38.6 million persons globally are living with HIV, of whom over 1.1 million reside in Zambia. Of the 2 million cases in the US, 64% of new cases among women are among African Americans. Alcohol and drug use represents a significant risk factor for HIV transmission among both Zambians and African Americans. In addition, gender dynamics in both the US and Zambia promote transmission. This study examines two interventions targeting HIV risk behavior among HIV positive substance users, women in Miami, USA (the New Opportunities for Women (NOW) Project) and men in Lusaka, Zambia (the Partner Project). The study compares the efficacy of these two culturally tailored sexual behavior interventions provided in group and individual session formats. US and Zambian participants increased sexual barrier use and reduced substance-related sexual risk. Comparatively greater gains were made by higher risk Zambian males than US females in both group and individual conditions. Among lower risk participants, women in the group condition achieved and sustained the greatest comparative risk reductions. Results suggest that cost effective group HIV transmission risk reduction interventions for multiethnic individuals can be successfully implemented among both female and male drug and alcohol users in multinational settings.     

Accumulation of somatic mutants in the B cell compartment after primary immunization with a T cell-dependent antigen.

The accumulation of somatic mutants in splenic B lymphocytes early after primary immunization with the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) coupled to chicken gamma globulin (CG) was determined. Rearranged V186.2 heavy chain genes were amplified by the polymerase chain reaction from genomic DNA and subjected to nucleotide sequence analysis. Somatic antibody mutants become detectable on day 6 after immunization, and most of the somatic mutations accumulating in the memory compartment are introduced until day 14. At this time strong selection for mutants expressing high binding affinity for NP is apparent. Extrapolation from the mutation frequency increases between day 6 and day 14 to the previously determined mutation frequency at week 6 (Weiss. U. and Rajewsky, K., J. Exp. Med. 1990, 172: 1681) leads to the prediction that the process of mutant generation ceases to operate around day 22 after primary immunization.     

A Novel Extravascular Input Function for the Assessment of Drug Absorption in Bioavailability Studies

Purpose. Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies. Methods. The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters. Results. Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time. Conclusions. The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.     

Blood flow, O2 extraction and O2 consumption along the rat small intestine

Differences in O2 delivery and consumption along the fed and fasted small intestine are described. Total wall blood flow was determined in sequential segments of small intestine from 5 to 6-month-old male, anesthetized Fischer 344 rats either 75-80 min before or after feeding, using radioactive microspheres. Oxygen saturation in submucosal arterioles and venules (50-60 micron diam) was determined throughout the intestine, using a microspectrophotometric technique. Venous O2 saturations showed considerable heterogeneity in all regions, and ranged from 0 to 77%. Arterial-venous O2 content differences (CaO2-CvO2) did not change along the fasted rat intestine, and averaged 8.2 ml O2/100 ml blood. However, CaO2-CvO2 followed a small proximal to distal gradient (proximal greater than distal) in the fed rats. Larger proximal to distal gradients (proximal greater than distal) occurred in both blood flow and O2 consumption in both groups. Feeding did not change intestinal average CaO2-CvO2. However, feeding induced a 53% increase in average O2 consumption, with the greatest increase (130%) occurring in the middle third of the intestine. Feeding induced a 42% increase in average blood flow, with the greatest increase (70%) occurring in the distal third of the intestine. The increased O2 used by the fed intestine was primarily provided by the increased blood flow. The O2 consumption gradient is assumed to reflect differences in mucosal mass along the intestine and/or differences in metabolic activity.     

Lobe of origin in the attribution of lung cancer to asbestos.

Lung cancer originates most commonly in the upper lobes in the general population but among workers with asbestosis it is most common in the lower lobes. Published data on lobar distribution were used to estimate the probabilities that lung cancer among asbestos workers is attributable to exposure to asbestos. This attribution varies directly with the relative risk. Critical values of the relative risk at which attribution of lung cancer to asbestos equalled its attribution to other causes, mainly smoking, were calculated. At a relative risk above 2.81 upper lobe cancers were more likely to be due to asbestos than not. For middle and lower lobe cancers, the critical relative risk was 1.55. These critical values were compared with published standardised mortality ratios reported for cohorts of workers with asbestosis. Since the ratios ranged from 6.3 to 9.1, the probability that lung cancer in such cases is due to asbestos is high regardless of lobe of origin. In many cohorts unstratified by the presence or absence of asbestosis the risk ratios are below one or both of these critical values. Since risk ratios are so high among workers with asbestosis, the ratios must be lower for workers without asbestosis than the overall ratios for unstratified cohorts. Therefore, the critical values may be useful in workers without asbestosis among such cohorts to estimate the upper limit of the probability that lung cancer in a given lobe is due to exposure to asbestos.     

Cardiomyopathy: a late complication of hemolytic uremic syndrome

This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS. Received February 12, 1996; received in revised form and accepted August 22, 1996     

Retinoic acid induced heparin-binding protein expression and localization during gastrulation,neurulation, and organogenesis

Retinoic acid induced heparin-binding protein (RIHB) is a highly basic, soluble polypeptide of the chick embryonic extracellular matrix. We have examined the expression and localization of RIHB during very early embryogenesis by in situ hybridization and immunohistochemistry. RIHB mRNA is very weakly detectable above background in the blastodiscs of unincubated eggs. The expression increases greatly over the first 24 hours of incubation, and is observed throughout the blastodisc in all three of the germ layers following gastrulation. As neurulation occurs, the expression becomes more restricted to certain areas, notably the ectoderm, the neural folds, and especially the notochord. After the neural tube has formed the expression in the tube itself decreases dramatically, whereas the expression in the head ectoderm and the notochord persists. After 72 hours of incubation expression remains relatively high throughout most of the embryo, with higher levels of expression in regions undergoing organogenesis and lower levels in organs which have already differentiated. RIHB protein is also weakly detectable in unincubated eggs as patches of immunoreactive material between the blastodisc and the vitelline. After 6 hours of incubation small regions of basement membrane are immunoreactive. RIHB is detected in this matrix, apparently before even fibronectin. The amount of RIHB protein increases dramatically over the first 24 hours of incubation. It is found in basement membrane separating the epiblast from the hypoblast, then later in that separating the ectoderm from the mesoderm. It is also detected surrounding individual cells, especially of the ectodermal layer. During neurulation RIHB is observed in the basement membrane surrounding the neural fold and the notochord, and in the lamina separating the ectodermal, mesodermal, and endodermal layers. Later in development, RIHB is detected in the basement membrane under the epidermis, throughout the developing limbs, and in the lamina of various developing organs, such as the eye, the pulmonary bud, the intestine, and the mesonephros. These results demonstrate that RIHB is highly expressed during the early embryonic period, by all three germ layers, and is an important and very early component of the embryonic extracellular matrix. Its very broad expression and localization argue for a more general role in development than its demonstrated weak neurotrophic activity. © 1994 Wiley-Liss, Inc.