Genetic risk score does not correlate with body mass index of Latina women in a clinical trial

Obesity disproportionately affects Latina women. Common genetic variants are convincingly associated with body mass index (BMI) and may be used to create genetic risk scores (GRS) for obesity that could define genetically influenced forms of obesity and alter response to clinical trial interventions. The objective of this study was (1) to identify the frequency and effect size of common obesity genetic variants in Latina women; (2) to determine the clinical utility of a GRS for obesity with Latina women participating in a community-based clinical trial. DNA from 85 Latina women was genotyped for eight genetic variants previously associated with BMI in Caucasians, but not yet assessed in Latina populations. The main outcome measure was the correlation of GRS (sum of eight risk alleles) with BMI, waist circumference, and percent body fat. A majority (83%) of participants had a BMI ≥25. Frequency of loci near FTO, MC4R, and GNPDA2 were lower in Latinas than Caucasians. Association of each locus with BMI was lower in Latinas compared to Caucasians with no significant correlations with BMI. We conclude that an eight locus GRS has no clinical utility for explaining obesity or predicting response to intervention in Latina women participating in a clinical trial.     

Electric shock: Cardiac effects relative to non fatal injuries and post-mortem findings in fatal cases

The documented cardiovascular effects of an electrical shock include acute myocardial necrosis, myocardial ischemia with or without necrosis, heart failure, arrhythmias, haemorrhagic pericarditis, acute hypertension with peripheral vasospasm and anomalous, non specific ECG alterations. Studies documenting the development of acute left ventricular failure and pulmonary oedema sustain that the observed ECG changes are secondary to myocardial injury. The cause of death of victims of instantly fatal electrical accidents is ventricular fibrillation, but it is not clear if this fibrillation is due to purely electrophysiological changes or to identifiable structural abnormalities in the heart. Little is known about the morphological changes in the heart, as differing anatomical alterations are described. Data from such studies may aid in a more accurate comprehension of clinical and morphological alterations of the heart and in the development of therapeutic strategies that could counterbalance such effects.     

A six-year follow-up of schoolchildren for urinary and intestinal schistosomiasis and soil-transmitted helminthiasis in Northern Tanzania

Two cross-sectional studies with a 6-year interval were undertaken in two primary schools in neighbouring villages in Mwanga District, Tanzania, to determine the prevalence of schistosome and soil-transmitted helminth infections before and 6 years after treatment. Within this interval, health-related interventions such as one mass treatment of the villagers, health education, improvement of sanitation and access to safe water were undertaken in the villages. In 1996, urinary schistosomiasis occurred in Kileo (n=284) and Kivulini (n=350) in 37.0 and 86.3% of the schoolchildren. Intestinal schistosomiasis was found in 22.9 and 43.5% of the children. The infection with soil-transmitted helminths ranged between 2.7 and 18.1% in both villages. After 6 years, the prevalence of urinary schistosomiasis in schoolchildren remained nearly constant in Kileo (33.5%; n=544), but dropped from 86.3% to 70.0% in Kivulini (n=514). In the latter village the proportion of children heavily infected with Schistosoma haematobium (> or = 50 eggs/10 ml urine) decreased from 53.8% to 34.4%. With the exception of hookworm infection, soil-transmitted helminthiasis and intestinal schistosomiasis were significantly less seen in 2002 compared to the baseline. The previous chemotherapy of schoolchildren and villagers in 1996 and 1998, respectively, might have led to a reduced transmission of schistosomiasis in the following years. However, the reduction of prevalence of soil-transmitted helminthiasis is more likely to be the result of health-related interventions.     

High Mycoplasma genitalium organism burden is associated with shedding of HIV-1 DNA from the cervix

We assessed the relationship between infection with Mycoplasma genitalium, an emerging sexually transmitted pathogen, and cervical shedding of human immunodeficiency virus (HIV)-1 DNA among 303 HIV-1-positive Kenyan women. HIV-1 shedding was detected by qualitative polymerase chain reaction (PCR) in 154 women (51%); M. genitalium was detected by qualitative PCR in 52 (17%), and organism burden was determined by quantitative PCR. Women with high M. genitalium organism burdens (more than the median of 3195 genomes/mL) were 3-fold more likely to shed HIV-1 DNA than were M. genitalium-negative women (adjusted OR, 2.9 [95% confidence interval, 1.1-7.6]), yet this did not appear to be mediated by traditional measures of cervical inflammation (elevated polymorphonuclear leukocyte count).     

Negotiating compliance in heart failure: remaining issues and questions.

Living with heart failure (HF) means living with a chronic illness characterized by periods of acute decompensation alternating with periods of relative stability. Improved medical care for patients with cardiovascular diseases, coupled with the aging of the populations in the developed world, has resulted in a steadily increasing prevalence of HF. Rehospitalization rates are high for this patient population. In 20-64% of the cases, poor compliance by patients with the prescribed HF treatment is a contributing factor to hospitalization. This article uses a review of the literature on HF non-compliance, including the prevalence, barriers, consequences, and the long-term outcomes of non-compliance with HF therapy, to illustrate remaining issues and questions. Original studies published in English or German between 1966 and June 2004 identified by combining patient compliance, non-compliance, adherence, self-care, rehospitalization, patient education, and management programs, with heart failure in the search strategy are included. Creative approaches to achieving a true partnership between providers and patients are needed if clinical outcomes are to improve.     

Epidemiological and ecological aspects related to malaria in the area of influence of the lake at Porto Primavera dam, in western São Paulo State, Brazil

A study was carried out in the area of influence of the Porto Primavera Hydroelectric Power Station, in western S?o Paulo State, to investigate ecological and epidemiological aspects of malaria in the area and monitor the profile of the anopheline populations following the environmental changes brought about by the construction of the lake. Mosquitoes captured were analyzed by standardized indicator species analysis (ISA) before and during different flooding phases (253 m and 257 m elevations). The local human population was studied by means of parasitological (thin/thick blood smears), molecular (PCR) and serological tests. Serological tests consisted of Enzyme Linked Immunosorbent Assay (ELISA) with synthetic peptides of the circumsporozoite protein (CSP) from classic Plasmodium vivax, P. vivax variants (VK247 and "vivax-like"), P. malariae and P. falciparum and Indirect Immunofluorescence Assay (IFA) with asexual forms of P. vivax, P. malariae and P. falciparum. The results of the entomological survey indicated that, although the Anopheles darlingi population increased after the flooding, the population density remained very low. No malaria, parasite infection or DNA was detected in the inhabitants of the study area. However, there was a low frequency of antibodies against asexual forms and a significant prevalence of antibodies against P. vivax, P. vivax variants, P. falciparum and P. malariae; the presence of these antibodies may result from recent or less recent contact with human or simian Plasmodium (a parallel study in the same area revealed the existence of a sylvatic cycle). Nevertheless, these results suggest that, as in other places where malaria is present and potential vectors circulate, the local epidemiological conditions observed could potentially support the transmission of malaria in Porto Primavera Lake if infected individuals are introduced in sufficient numbers. Further studies are required to elucidate the phenomena described in this paper.     

The discovery of α1-antitrypsin and its role in health and disease

α1-Antitrypsin (AAT) is the archetype member of the serine protease inhibitor (SERPIN) supergene family. The AAT deficiency is most often associated with the Z mutation, which results in abnormal Z AAT folding in the endoplasmic reticulum of hepatocytes during biogenesis. This causes intra-cellular retention of the AAT protein rather than efficient secretion with consequent deficiency of circulating AAT. The reduced serum levels of AAT contribute to the development of chronic obstructive pulmonary disease (COPD) and the accumulation of abnormally folded AAT protein increases risk for liver diseases. In this review we show that with the discovery of AAT deficiency in the early 60s as a genetically determined predisposition to the development of early-onset emphysema, intensive investigations of enzymatic mechanisms that produce lung destruction in COPD were pursued. To date, the role of AAT in other than lung and liver diseases has not been extensively examined. Current findings provide new evidence that, in addition to protease inhibition, AAT expresses anti-inflammatory, immunomodulatory and antimicrobial properties, and highlight the importance of this protein in health and diseases. In this review co-occurrence of several diseases with AAT deficiency is discussed.     

Novel therapeutic strategies in multiple myeloma: role of the heat shock protein inhibitors

Despite advances in understanding the molecular pathogenesis of multiple myeloma and promising new therapies, almost all patients eventually relapse with resistant disease. There is therefore a strong rationale for combining novel therapies that target intrinsic molecular pathways mediating multiple myeloma cell resistance. One such protein family is the heat shock proteins (HSP), especially the HSP90 family. Heat shock protein inhibitors have been identified as promising cancer treatments as, while they only inhibit a single biologic function, the chaperone-protein association, their effect is widespread as it results in the destruction of numerous client proteins. This article reviews the preclinical and clinical data, which support the testing of HSP90 inhibitors as cancer drugs and update the reader on the current status of the ongoing clinical trials of HSP90 inhibitors in multiple myeloma.     

Prognosis in the thrombolysis in myocardial ischemia III registry according to the Braunwald unstable angina pectoris classification

The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included. Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP. Clinical end points were compared at 6 weeks and 1 year. Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (4.1% vs 6.4% vs 13.4%, respectively; p <0.001) and 1 year (9.7% vs 16.7% vs 19.7%; p <0.001). Recurrent ischemia at 6 weeks followed the same gradient (13.2% vs 18.5% vs 20.8%; p <0.001). Patients with secondary UAP had similar extent of disease at angiography as primary UAP. Patients with nonresting UAP had lower rates of death or MI than patients with UAP at rest (3.0% vs 5.6%, p = 0.011 at 6 weeks, and 8.2% vs 12.5%, p = 0.004 at 1 year). Patients with ST-segment deviation and those who had received prior antianginal medical treatment also had worse outcomes. Thus, the Braunwald classification of UAP predicts prognosis with secondary UAP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events. Given their high risk for adverse events, patients with secondary UAP should be treated aggressively.