Astrocyte specific viral strains in HIV dementia

We molecularly characterized human immunodeficiency virus type 1 (HIV-1) present in pure populations of astrocytes, macrophages, and multinucleated giant cells isolated using laser capture microdissection from brain tissue of two patients who died with HIV-associated dementia. The V3 region of the HIV-1 envelope (env) gene was amplified from the pure-cell populations, and multiple clones were sequenced. In both patients, the V3 env sequences were distinct in astrocytes compared with neighboring macrophages or multinucleated giant cells and were characteristic of CCR5-using (R5) HIV-1. These results demonstrate cell-specific compartmentalization of distinct R5-like viral strains in the central nervous system microenvironment.     

Safety reporting in randomized trials of mental health interventions

OBJECTIVE: The authors aimed to evaluate the adequacy of the reporting of safety information in publications of randomized trials of mental-health-related interventions. METHOD: The authors randomly selected 200 entries from the PsiTri registry of mental-health-related controlled trials. This yielded 142 randomized trials that were analyzed for adequacy and relative emphasis of their content on safety issues. They examined drug trials as well as trials of other types of interventions. RESULTS: Across the 142 eligible trials, 103 involved drugs. Twenty-five of the 142 trials had at least 100 randomly chosen subjects and at least 50 subjects in a study arm. Among drug trials, only 21.4% had adequate reporting of clinical adverse events, and only 16.5% had adequate reporting of laboratory-determined toxicity, while 32.0% reported both the numbers and the reasons for withdrawals due to toxicity in each arm. On average, drug trials devoted 1/10 of a page in their results sections to safety, and 58.3% devoted more space to the names and affiliations of authors than to safety. None of the trials of nondrug interventions had adequate or even partially adequate reporting of either clinical adverse events or laboratory-determined toxicity. In multivariate modeling, long-term trials and trials conducted in the United States devoted even less space to safety, while schizophrenia trials devoted more space to safety than did trials in other areas. CONCLUSIONS: Safety reporting is largely neglected across trials of mental-health-related interventions, thus hindering the assessment of risk-benefit ratios for rational decision making in mental health care.     

Proteotypic classification of spontaneous and transgenic mammary neoplasms

Introduction  

Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation.     

Left-colon antegrade continence enema (LACE) procedure for fecal incontinence

Purpose: Antegrade continence enemas (ACE) are an efficacious therapeutic option for patients with fecal incontinence. The authors review their institution’s experience with a variation of the Monti-Malone ACE procedure using the left colon as a source of an intestinal conduit and enema reservoir.Methods: From 2000 to 2002, 18 patients with fecal incontinence or intractable constipation underwent left-colon ACE (LACE) procedure. Concomitant Mitrofanoff appendicovesicostomy was performed in 15 patients and bladder augmentation in 9. The majority of patients had neural tube defects. A segment of left colon was tubularized, tunneled into the muscular wall of the distal colon, and exteriorized through the left upper quadrant or midabdomen. Stomal catherization and enema installation were started one month postoperatively.Results: Fifteen patients (83%) achieved fecal continence, 2 remain incontinent of stool, and 1 experienced stomal closure (mean follow-up was 24 ± 9 months). Two patients had stomal stenosis that required revision. The mean enema volume in patient’s achieving continence was 360 ± 216 mL, and the mean transit time was 18 ± 12 minutes.Conclusions: LACE is an efficacious procedure for fecal incontinence that can be performed safely at the time of major urologic reconstruction. Administration of enemas into the left colon has several physiologic advantages that result in predictable bowel evacuation.     

Pharmacological treatment of hypertension in pregnancy

The hypertensive disorders of pregnancy complicate 5-10% of pregnancies. Of these disorders 70% are pregnancy related (preeclampsia-eclampsia and gestation hypertension) and 30 % are a pre-existing hypertensive condition (chronic hypertension). These disorders are associated with maternal and fetal complications and have a substantial economic impact. This review examined the pharmacological treatment of the hypertensive disorders of pregnancy. There is a general consensus that anti-hypertensive should be given with severe hypertension and this should be in the hospital. The value of antihypertensive drugs in pregnant women with mild hypertension continues to be an area of debate that the evidence is too scanty to securely evaluate the clinical benefits of treating mild hypertension during pregnancy. The choice of the antihypertensive agents depends on individual clinician preference, the specified maternal and foetal benefits and the reproductive complications (teratogenisity, fetotoxicity and neonatal toxicity) of each particular agent. There are unequivocal evidences that Magnesium sulphate is superior to other agents in reducing recurrent eclamptic seizures. There is a strong recent evidence recommended that magnesium sulphate should be considered for women with pre-eclampsia for whom there is concern about the risk of eclampsia.     

Strengthening capacity in developing countries for evidence-based public health: the data for decision-making project

Public health officials and the communities they serve need to: identify priority health problems; formulate effective health policies; respond to public health emergencies; select, implement, and evaluate cost-effective interventions to prevent and control disease and injury; and allocate human and financial resources. Despite agreement that rational, data-based decisions will lead to improved health outcomes, many public health decisions appear to be made intuitively or politically. During 1991-1996, the US Centers for Disease Control and Prevention implemented the US Agency for International Development funded Data for Decision-Making (DDM) Project. DDM goals were to: (a) strengthen the capacity of decision makers to identify data needs for solving problems and to interpret and use data appropriately for public health decisions; (b) enhance the capacity of technical advisors to provide valid, essential, and timely data to decision makers clearly and effectively; and (c) strengthen health information systems (HISs) to facilitate the collection, analysis, reporting, presentation, and use of data at local, district, regional, and national levels. Assessments were conducted to identify important health problems, problem-driven implementation plans with data-based solutions as objectives were developed, interdisciplinary, in-service training programs for mid-level policy makers, program managers, and technical advisors in applied epidemiology, management and leadership, communications, economic evaluation, and HISs were designed and implemented, national staff were trained in the refinement of HISs to improve access to essential data from multiple sources, and the effectiveness of the strategy was evaluated. This strategy was tested in Bolivia, Cameroon, Mexico, and the Philippines, where decentralization of health services led to a need to strengthen the capacity of policy makers and health officers at sub-national levels to use information more effectively. Results showed that the DDM strategy improved evidence-based public health. Subsequently, DDM concepts and practices have been institutionalized in participating countries and at CDC.     

Validation and reproducibility of computerised cell-viability analysis of tissue slices

Background

The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results.

Methods

To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups – unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes.

Results

Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77).

Conclusions

This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.