HIV immunotherapy comes of age: implications for prevention,treatment and cure

Antiretroviral therapy (ART) has reshaped the lives of millions of individuals infected with human immunodeficiency virus (HIV). Patients initiating ART early in the course of infection benefit from a considerable reduction in the risks of acquired immune deficiency syndrome (AIDS) and HIV-related inflammatory events. However, the absence of cure and lifelong requirements of treatment highlight the need of a vaccine and an immunotherapeutic strategy. Like for cancer, a paradigm shift has occurred with the contribution of immune activation and microbial translocation priming aberrant systemic immunity in restricting the ability of the host to mount an effective immune response. The approaches of implementing an effective vaccine to prevent infection and inhibition of immune activation with breakage of viral latency followed by vaccination should lead to an HIV-free generation.     

A new and automated method for objective analysis of detrusor rhythm during the filling phase

Introduction

There is growing acceptance that the detrusor muscle is not silent during the filling phase of the micturition cycle but displays low-amplitude phasic contractions that have been associated with urinary urgency. Unfortunately, there is currently no standardized methodology to quantify detrusor rhythm during the filling phase. Therefore, the purpose of this study was to develop an automated computer algorithm to analyze rat detrusor rhythm in a quick, accurate, and reproducible manner.

Materials and methods

Strips of detrusor smooth muscle from rats (n = 17) were placed on force transducers and subjected to escalating doses of PGE₂ to generate contractile rhythm tracings. An automated computer algorithm was developed to analyze contractile frequency, amplitude, and tone on the generated rhythm tracings. Results of the automated computerized analysis were compared to human (n = 3) interpretations. Human interpreters manually counted contractions and then recounted the same data two weeks later. Intra-observer, inter-observer, and human-to-computer comparisons were performed.

Results

The computer algorithm quantified concentration-dependent changes in contractile frequency, amplitude, and tone after administration of PGE₂ (10^?9–10^?6M). Concentration–response curves were similar for all contractile components with increases in frequency identified mainly at physiologic concentrations of PGE₂ and increases in amplitude at supra-physiologic concentrations. The computer algorithm consistently over-counted the human interpreters, but with less variability. Differences in inter-observer consistency were statistically significant.

Conclusions

Our computerized algorithm accurately and consistently identified changes in detrusor muscle contractile frequency, amplitude, and tone with varying doses of PGE₂. Frequency counts were consistently higher than those obtained by human interpreters but without variability or bias. Refinements of this method may allow for more standardized approach in the study of pharmacologic agents on filling phase rhythmic activity.     

"Were-wolf" cutaneous tuberculosis

Lupus vulgaris is a variant of cutaneous tuberculosis. Its more destructive and mutilating clinical forms have become rarer in consonance of a general decline of cutaneous tuberculosis. It is rarely seen now in developed countries due to stringent control measures, improved quality of living and effective therapeutic regimens. Misdiagnosis, neglect, or late diagnosis may result in severe, ulcerative and mutilating "wolf eaten" skin lesions.This paper describes four such cases of "were-wolf" cutaneous tuberculosis. Early diagnosis and treatment is important to prevent much of the disfigurement.     

Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients

Data on 90 patients (55 adults and 35 children) with chronic idiopathic thrombocytopenic purpura (ITP) and a platelet count of <50 x 10(9)/L treated with dapsone at a dose of 1-2 mg/kg/d are presented. A response was observed in 57 (63.3%) patients. The average time for response was 3.5 months (range 1-9) and the average duration of treatment with dapsone was 10.4 months (range 4-14). Overall response rates of 65.7% and 61.8% were observed in children and adults respectively. Side effects requiring discontinuation of therapy were observed in three (2%) patients. These results demonstrate that dapsone is an effective, inexpensive and well-tolerated treatment for chronic ITP, in both children and adults and could be considered for patients who fail steroid therapy.