Regular smoking and asthma incidence in adolescents

RATIONALE: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence. OBJECTIVES: To determine whether regular smoking is associated with the new onset of asthma during adolescence. METHODS: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma. MEASUREMENTS AND MAIN RESULTS: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% CI], 1.7-8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% CI, 3.2-24.0). CONCLUSIONS: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.     

Quality of case reports of adverse drug reactions with psychotropic drugs: a 25‐year review

Case reports of adverse reactions with psychotropic drugs can be useful in raising hypotheses, to be tested with more rigorous study designs. However such reports have significant methodological drawbacks, making it hard to determine causality. We undertook a systematic assessment of the quality of case reports and small case series published within Human Psychopharmacology over 25 years. For reports of adverse drug reactions, modified Bradford Hill criteria for causality (for consistency, strength, specificity, temporal relationship and plausibility) were used to ascertain the quality of the account. Reports which had been cited at least 10 times by December 2010 were examined in detail, to assess their overall contribution in extending understanding and influencing clinical practice. Of 40 reports of adverse drug reactions, only seven were sufficiently robust for confidence in probable or possible causality. Nine reports had been cited more than 10 times: the five most frequently cited reports of adverse drug reactions described movement disorders, suicidal thoughts and discontinuation symptoms with SSRIs: clinical relevance was high, but their quality was not markedly greater than less frequently cited reports. Nearly all reports of adverse drug reactions, published in a single journal over 25 years, were insufficiently robust to demonstrate probable causality. Reports that are cited frequently become influential because of their potential clinical relevance, rather than due to their methodological quality. Copyright © 2013 John Wiley & Sons, Ltd.     

Stoichiometric imbalance in the receptor complex contributes to dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension

Heterozygous germline defects in a gene encoding a type II receptor for bone morphogenetic proteins (BMPR-II) underlie the majority of inherited cases of the vascular disorder known as pulmonary arterial hypertension (PAH). However, the precise molecular consequences of PAH causing mutations on the function of the receptor complex remain unclear. We employed novel enzymatic and fluorescence activity based techniques to assess the impact of PAH mutations on pre-mRNA splicing, nonsense-mediated decay (NMD) and receptor complex interactions. We demonstrate that nonsense and frameshift mutations trigger NMD, providing further evidence that haplo-insufficiency is a major molecular consequence of disease-related BMPR2 mutations. We identified heterogeneous functional defects in BMPR-II activity, including impaired type I receptor phosphorylation, receptor interactions and altered receptor complex stoichiometry leading to perturbation of downstream signalling pathways. Importantly, these studies demonstrate that the intracellular domain of BMPR-II is both necessary and sufficient for receptor complex interaction. Finally and to address the potential for resolution of stoichiometric balance, we investigated an agent that promotes translational readthrough of a BMPR2 nonsense reporter construct without interfering with the NMD pathway. We propose that stoichiometric imbalance, due to either haplo-insufficiency or loss of optimal receptor-receptor interactions impairs BMPR-II mediated signalling in PAH. Taken together, these studies have identified an important target for early therapeutic intervention in familial PAH.     

Molecular epidemiology of human herpesvirus 8 variants in Kaposi's sarcoma from Iranian patients

Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological and molecular information about HHV-8 variants circulating among the Iranian population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS biopsies from Iranian patients mainly affected by classic KS. DNA samples were subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K, respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out of 41) fall into the large C clade with only 2 belonging to the A clade. In conclusion, HHV-8 variants identified among classic Iranian KS are largely related to Eurasian genotypes previously identified in KS from Mediterranean, Middle East, and East Asian regions.     

Patient-Reported Outcome and Clinical Scores Are Equally Accurate in Predicting Mucosal Healing in Ulcerative Colitis: A Prospective Study

Digestive Diseases and Sciences - Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity. We aimed to determine how strong...