Increased prevalence of irritable bowel syndrome in patients with bronchial asthma

AbstractIrritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract. IBS may represent a primary disorder of gastrointestinal motility, accompanied with motor dysfunction in various extraintestinal sites. Recent studies suggest that IBS is associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS patients than in control subjects. The aim of our study was to assess the prevalence of IBS in a cohort of asthmatic patients. We evaluated 150 patients with bronchial asthma (71 males and 79 females, aged 45.1±14.9 years) and two control groups including 130 patients with other pulmonary disorder and 120 healthy subjects. All subjects enrolled (asthmatic and controls) completed the Greek version of the Bowel Disease Questionnaire (BDQ). BDQ is a, previously validated, self-report instrument to measure gastrointestinal symptoms. Diagnosis of IBS was based on Rome II criteria. The IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%,P <0.001) and healthy ones (25/120, 20.8%, P<0.001). For all subjects studied, the prevalence of IBS was significantly higher in females (78/214, 36.4%) than in males (38/186, 20.4%, P<0.001). The IBS prevalence in asthmatic males was 29.5% vs. 15.2% in male patients with other pulmonary disorders (P=0.002) and 14.2% in male healthy subjects (P=0.002). The IBS prevalence in asthmatic females was 51.8% vs. 28.1% in females patients with other pulmonary disorders (P<0.001) and 26.5% in females healthy subjects (P<0.001). None of the asthma medications were associated with increased or decreased likelihood of IBS. We conclude that patients with bronchial asthma have an increased prevalence of IBS. Further studies are needed to clarify the potential pathogenetic mechanisms underlying the association between IBS and asthma

Selection and Presentation of Imaging Figures in the Medical Literature

Background: Images are important for conveying information, but there is no empirical evidence on whether imaging figures are properly selected and presented in the published medical literature. We therefore evaluated the selection and presentation of radiological imaging figures in major medical journals. Methodology/Principal Findings: We analyzed articles published in 2005 in 12 major general and specialty medical journals that had radiological imaging figures. For each figure, we recorded information on selection, study population, provision of quantitative measurements, color scales and contrast use. Overall, 417 images from 212 articles were analyzed. Any comment/hint on image selection was made in 44 (11%) images (range 0–50% across the 12 journals) and another 37 (9%) (range 0–60%) showed both a normal and abnormal appearance. In 108 images (26%) (range 0–43%) it was unclear whether the image came from the presented study population. Eighty-three images (20%) (range 0–60%) had any quantitative or ordered categorical value on a measure of interest. Information on the distribution of the measure of interest in the study population was given in 59 cases. For 43 images (range 0–40%), a quantitative measurement was provided for the depicted case and the distribution of values in the study population was also available; in those 43 cases there was no over-representation of extreme than average cases (p = 0.37). Significance: The selection and presentation of images in the medical literature is often insufficiently documented; quantitative data are sparse and difficult to place in context

Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes

To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4[superscript +] T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell–specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer’s and Parkinson’s disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants

Sex-Specific Association of the Putative Fructose Transporter SLC2A9 Variants With Uric Acid Levels Is Modified by BMI

OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

BACKGROUND: Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. METHODS: We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. RESULTS: Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. CONCLUSIONS: Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis

Background: The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.Methods: In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls.Results: The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05).Conclusion: This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase