Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

Properties of Light Flavour Baryons in Hypercentral quark model

The light flavour baryons are studied within the quark model using the hyper central description of the three-body system. The confinement potential is assumed as hypercentral coulomb plus power potential ($hCPP_\nu$) with power index $\nu$. The masses and magnetic moments of light flavour baryons are computed for different power index, $\nu$ starting from 0.5 to 1.5. The predicted masses and magnetic moments are found to attain a saturated value with respect to variation in $\nu$ beyond the power index $\nu>$ 1.0. Further we computed transition magnetic moments and radiative decay width of light flavour baryons. The results are in good agreement with known experimental as well as other theoretical models.Comment: Accepted in Pramana J. of Physic

Risk of valvular heart disease associated with use of fenfluramine

BACKGROUND: Estimates of excess risk of valvular heart disease among prior users of fenfluramine and dexfenfluramine have varied widely. Two major forms of bias appear to contribute to this variability and also result in a systematic under-estimation of risk. The first, a form of nondifferential misclassification, is the result of including background, prevalent cases among both exposed and unexposed persons in calculations of risk. The second bias results from not considering the relatively short duration of exposure to drugs. METHODS: We examined data from all available echocardiographic studies reporting the prevalence of aortic regurgitation (AR) and mitral regurgitation (MR) among persons exposed to fenfluramine or dexfenfluramine and a suitable control group. We also included one study in which previously existing AR or MR had been excluded. We corrected for background prevalent cases, estimated incidence rates in unexposed persons, and performed a person-years analysis of apparent incidence rates based on exposure time to provide an unbiased estimate of relative risk. RESULTS: Appearance of new AR was strongly related to duration of exposure (R(2 )= 0.75, p < 0.0001). The summary relative risk for mild or greater AR was 19.6 (95% CI 16.3 – 23.5, p < 0.00001); for moderate or greater MR it was 5.9 (95% CI 4.0 – 8.6, p < 0.00001). CONCLUSION: These findings provide strong support for the view that fenfluramine and dexfenfluramine are potent causal factors in the development of both aortic and mitral valvular heart disease

Sero-prevalence and risk factors for hepatitis B virus infection among health care workers in a tertiary hospital in Uganda

BACKGROUND: Hepatitis B virus (HBV) infection is a global public health challenge. Prevalence of current hepatitis B virus infection in the general population in Uganda is about 10%. Health care workers (HCW) have an extra risk of getting infected from their workplace and yet they are not routinely vaccinated against HBV infection. This study aimed at estimating prevalence of hepatitis B virus infection and associated risk factors among health care workers in a tertiary hospital in Uganda. METHODS: Data were obtained from a cross sectional survey conducted in Mulago, a national referral and teaching hospital in Uganda among health care workers in 2003. A proportionate to size random sample was drawn per health care worker category. A structured questionnaire was used to collect data on socio-demographic characteristics and risk factors. ELISA was used to test sera for HBsAg, anti-HBs and total anti-HBc. Descriptive and logistic regression models were used for analysis. RESULTS: Among the 370 participants, the sero-prevalence of current hepatitis B virus infection was 8.1%; while prevalence of life time exposure to hepatitis B virus infection was 48.1%. Prevalence of needle stick injuries and exposure to mucous membranes was 67.8% and 41.0% respectively. Cuts were also common with 31.7% of doctors reporting a cut in a period of one year preceding the survey. Consistent use of gloves was reported by 55.4% of respondents. The laboratory technicians (18.0% of respondents) were the least likely to consistently use gloves. Only 6.2% of respondents were vaccinated against hepatitis B virus infection and 48.9% were susceptible and could potentially be protected through vaccination. Longer duration in service was associated with a lower risk of current infection (OR = 0.13; p value = 0.048). Being a nursing assistant (OR = 17.78; p value = 0.007) or a laboratory technician (OR = 12.23; p value = 0.009) were associated with a higher risk of current hepatitis B virus infection. Laboratory technicians (OR = 3.99; p value = 0.023) and individuals with no training in infection prevention in last five years (OR = 1.85; p value = 0.015) were more likely to have been exposed to hepatitis B virus infection before. CONCLUSIONS: The prevalence of current and life time exposure to hepatitis B virus infection was high. Exposure to potentially infectious body fluids was high and yet only a small percentage of HCW were vaccinated. There is need to vaccinate all health care workers as a matter of policy and ensure a safer work environment

Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals

<p>Abstract</p> <p>Background</p> <p>Use of fenfluramines for weight loss has been associated with the development of characteristic plaques on cardiac valves causing regurgitation. However, previously published studies of exposure to fenfluramines have been limited by relatively small sample size, short duration of follow-up, and the lack of any estimate of the frequency of subsequent valvular surgery. We performed an observational study of 5743 users of fenfluramines examined by echocardiography between July 1997 and February 2004 in a single large cardiology clinic.</p> <p>Results</p> <p>The prevalence of at least mild aortic regurgitation (AR) or moderate mitral regurgitation (MR) was 19.6% in women and 11.8% in men (<it>p </it>< 0.0001 for gender difference). Duration of use was strongly predictive of mild or greater AR (<it>p </it>< 0.0001 for trend), MR (<it>p </it>= 0.002), and tricuspid regurgitation (TR) (<it>p </it>< 0.0001), as was earlier scan date (<it>p </it>< 0.0001 for those scanned prior to 1 January 2000 versus later). Increasing age was also independently associated with increased risk of AR and MR (both <it>p </it>< 0.0001). With mean follow-up of 30.3 months, AR worsened in 15.2%, remained the same in 63.1%, and improved in 21.7%. Corresponding values for MR were 24.8%, 47.4% and 27.9%. Pulmonary hypertension was strongly associated with MR but not AR. Valve surgery was performed on 38 patients (0.66% of 5743), 25 (0.44%) with clear evidence of fenfluramine-related etiology.</p> <p>Conclusion</p> <p>Regurgitant valvulopathy was common in individuals exposed to fenfluramines, more frequent in females, and associated with duration of use in all valves assessed. Valve surgery was performed as frequently for aortic as mitral valves and some tricuspid valve surgeries were also performed. The incidence of surgery appeared to be substantially increased compared with limited general population data.</p

Chicken TREM-B1, an Inhibitory Ig-Like Receptor Expressed on Chicken Thrombocytes

Triggering receptors expressed on myeloid cells (TREM) form a multigene family of immunoregulatory Ig-like receptors and play important roles in the regulation of innate and adaptive immunity. In chickens, three members of the TREM family have been identified on chromosome 26. One of them is TREM-B1 which possesses two V-set Ig-domains, an uncharged transmembrane region and a long cytoplasmic tail with one ITSM and two ITIMs indicating an inhibitory function. We generated specific monoclonal antibodies by immunizing a Balb/c mouse with a TREM-B1-FLAG transfected BWZ.36 cell line and tested the hybridoma supernatants on TREM-B1-FLAG transfected 2D8 cells. We obtained two different antibodies specific for TREM-B1, mab 7E8 (mouse IgG1) and mab 1E9 (mouse IgG2a) which were used for cell surface staining. Single and double staining of different tissues, including whole blood preparations, revealed expression on thrombocytes. Next we investigated the biochemical properties of TREM-B1 by using the specific mab 1E9 for immunoprecipitation of either lysates of surface biotinylated peripheral blood cells or stably transfected 2D8 cells. Staining with streptavidin coupled horse radish peroxidase revealed a glycosylated monomeric protein of about 50 kDa. Furthermore we used the stably transfected 2D8 cell line for analyzing the cytoplasmic tyrosine based signaling motifs. After pervanadate treatment, we detected phosphorylation of the tyrosine residues and subsequent recruitment of the tyrosine specific protein phosphatase SHP-2, indicating an inhibitory potential for TREM-B1. We also showed the inhibitory effect of TREM-B1 in chicken thrombocytes using a CD107 degranulation assay. Crosslinking of TREM-B1 on activated primary thrombocytes resulted in decreased CD107 surface expression of about 50-70%

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

Epidemic History and Evolutionary Dynamics of Hepatitis B Virus Infection in Two Remote Communities in Rural Nigeria

BACKGROUND: In Nigeria, hepatitis B virus (HBV) infection has reached hyperendemic levels and its nature and origin have been described as a puzzle. In this study, we investigated the molecular epidemiology and epidemic history of HBV infection in two semi-isolated rural communities in North/Central Nigeria. It was expected that only a few, if any, HBV strains could have been introduced and effectively transmitted among these residents, reflecting limited contacts of these communities with the general population in the country. METHODS AND FINDINGS: Despite remoteness and isolation, approximately 11% of the entire population in these communities was HBV-DNA seropositive. Analyses of the S-gene sequences obtained from 55 HBV-seropositive individuals showed the circulation of 37 distinct HBV variants. These HBV isolates belong predominantly to genotype E (HBV/E) (n=53, 96.4%), with only 2 classified as sub-genotype A3 (HBV/A3). Phylogenetic analysis showed extensive intermixing between HBV/E variants identified in these communities and different countries in Africa. Quasispecies analysis of 22 HBV/E strains using end-point limiting-dilution real-time PCR, sequencing and median joining networks showed extensive intra-host heterogeneity and inter-host variant sharing. To investigate events that resulted in such remarkable HBV/E diversity, HBV full-size genome sequences were obtained from 47 HBV/E infected persons and P gene was subjected to Bayesian coalescent analysis. The time to the most recent common ancestor (tMRCA) for these HBV/E variants was estimated to be year 1952 (95% highest posterior density (95% HPD): 1927-1970). Using additional HBV/E sequences from other African countries, the tMRCA was estimated to be year 1948 (95% HPD: 1924-1966), indicating that HBV/E in these remote communities has a similar time of origin with multiple HBV/E variants broadly circulating in West/Central Africa. Phylogenetic analysis and statistical neutrality tests suggested rapid HBV/E population expansion. Additionally, skyline plot analysis showed an increase in the size of the HBV/E-infected population over the last approximately 30-40 years. CONCLUSIONS: Our data suggest a massive introduction and relatively recent HBV/E expansion in the human population in Africa. Collectively, these data show a significant shift in the HBV/E epidemic dynamics in Africa over the last century