A pilot double‐blind randomised placebo‐controlled trial of the effects of fixed‐dose combination therapy (‘polypill’) on cardiovascular risk factors

Aim: Our objective was to investigate the effects and tolerability of fixed‐dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels. Methods: This was a double‐blind randomised placebo‐controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8‐week placebo run‐in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed‐dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL‐cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention‐to‐treat basis. Results: At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL‐cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels. Conclusion: The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.     

Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma

The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies. A previous study from China suggested that BRCA2 might play a role in the etiology of ESCC. We screened for mutations in the coding region of the BRCA2 gene in the germline DNA of 197 Turkmen patients with ESCC. A nonsense variant, K3326X, was identified in 9 of 197 cases (4.6%) vs 2 of 254 controls (0.8%) (OR=6.0, 95% CI=1.3-28; P=0.01). This mutation leads to the loss of the C-terminal domain of the BRCA2 protein, a part of the region of interaction with the FANCD2 protein. We observed nine other BRCA2 variants in single cases only, including two deletions, and seven missense mutations. Six of these were judged to be pathogenic. In total, a suspicious deleterious BRCA2 variant was identified in 15 of 197 ESCC cases (7.6%).     

Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran

The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (+/-2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05-2.73), in those who used opium only (2.12, 1.21-3.74), and in those who used both tobacco and opium (2.35, 1.50-3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.     

Brugia malayi infective larvae fail to activate Langerhans cells and dermal dendritic cells in human skin

Filarial infection in humans is initiated when a mosquito deposits third‐stage parasite larvae (L3) in the skin. Langerhans cells (LCs) and dermal dendritic cells (DDCs) are the first cells that the parasite encounters, and L3s must evade these highly effective antigen‐presenting cells to establish infection. To assess LC and DDC responses to L3 in human skin, we employed three models of increasing physiologic relevance: in vitro‐generated LCs, epidermal blister explants and full‐thickness human skin sections. In vitro‐generated LCs expressed TLR1‐10 and robustly produced IL‐6 and TNF‐α in response to PolyI:C, but pre‐exposure to L3s did not alter inflammatory cytokine production or TLR expression. L3s did not modulate expression of LC markers CDH1, CD207, or CD1a, or the regulatory products TSLP or IDO in epidermal explants or in vitro‐generated LC. LC, CD14+ DDC, CD1c+ DC and CD141+ DC from human skin sections were analysed by flow cytometry. While PolyI:C potently induced CCL22 production in LC, CD1c+ DC, and CD141+ DC, and IL‐10 production in LC, L3s did not modulate the numbers of or cytokine production by any skin DC subset. L3s broadly failed to activate or modulate LCs or DDCs, suggesting filarial larvae expertly evade APC detection in human skin.     

Hepatitis B/C virus co-infection in Iran: A seroepidemiological study.

Background/aims: As hepatitis B and C virus have the same transmission routes, dual infection may occur. The aim of this study was to determine the seroprevalence of HCV in HBsAg-positive subjects. Methods: 139 HBsAg-positive subjects were enrolled in the study. Serum samples were tested using ELISA method for anti-HCV antibodies. Chi-square and Fisher's exact tests were used to compare the proportions. Results: There were 68 (48.9%) males and 71 (51.1%) females. The mean age was 41.89+/-11.30 years. One case was excluded because of inadequate blood sampling. Anti-HCV antibody was positive in 17 (12.3%) of the 138 remaining subjects. Seropositivity of HCV was similar between female and male patients (p=0.69). Conclusion: The seroprevalence of co-infection with hepatitis B virus and hepatitis C virus in our study was higher than such reports from some countries (Italy), but was in line with worldwide prevalence (>10%).     

Terrorist attacks in the largest metropolitan city of Pakistan: Profile of soft tissue and skeletal injuries from a single trauma center

BACKGROUND: Pakistan has been hugely struck with massive bomb explosions(car and suicide bombs) resulting in multiple casualties in the past few years. The aim of this study is to present the patterns of skeletal and soft tissue injuries and to review the outcome of the victims who presented to our hospital.METHODS: This is a retrospective chart review from January 2008 to December 2012. The medical record numbers of patients were obtained from the hospital Health Information and Management Sciences(HIMS) as per the ICD-9 coding.RESULTS: During the study period, more than 100 suicide and implanted bomb blast attacks took place in the public proceedings, government offices, residential areas and other places of the city. Altogether 262 patients were enrolled in the study. The mean age of the patients was 31±14 years. The shrapnel inflicted wounds were present on to the upper limb in 24 patients and the lower limb in 50.CONCLUSION: Long bone fractures were the most common skeletal injuries. The fractures were complicated by penetrating fragments and nails which result in post operative infections and prolonged hospital stay.     

Synteny perturbations between wheat homoeologous chromosomes caused by locus duplications and deletions correlate with recombination rates

Loci detected by Southern blot hybridization of 3,977 expressed sequence tag unigenes were mapped into 159 chromosome bins delineated by breakpoints of a series of overlapping deletions. These data were used to assess synteny levels along homoeologous chromosomes of the wheat A, B, and D genomes, in relation to both bin position on the centromere-telomere axis and the gradient of recombination rates along chromosome arms. Synteny level decreased with the distance of a chromosome region from the centromere. It also decreased with an increase in recombination rates along the average chromosome arm. There were twice as many unique loci in the B genome than in the A and D genomes, and synteny levels between the B genome chromosomes and the A and D genome homoeologues were lower than those between the A and D genome homoeologues. These differences among the wheat genomes were attributed to differences in the mating systems of wheat diploid ancestors. Synteny perturbations were characterized in 31 paralogous sets of loci with perturbed synteny. Both insertions and deletions of loci were detected and both preferentially occurred in high recombination regions of chromosomes.     

Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage

T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCRalphabeta, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3zeta, p56lck, p59fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon-gamma (IFN-gamma), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3zeta, p56lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN-gamma, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions.