163 research outputs found
Cardiac arrest due to lymphocytic colitis: a case report
<p>Abstract</p> <p>Introduction</p> <p>We present a case of cardiac arrest due to hypokalemia caused by lymphocytic colitis.</p> <p>Case presentation</p> <p>A 69-year-old Caucasian man presented four months prior to a cardiac arrest with watery diarrhea and was diagnosed with lymphocytic colitis. Our patient experienced a witnessed cardiac arrest at his general practitioner's surgery. Two physicians and the emergency medical services resuscitated our patient for one hour and four minutes before arriving at our university hospital. Our patient was defibrillated 16 times due to the recurrence of ventricular tachyarrhythmias. An arterial blood sample revealed a potassium level of 2.0 mmol/L (reference range: 3.5 to 4.6 mmol/L) and pH 6.86 (reference range: pH 7.37 to 7.45). As the potassium level was corrected, the propensity for ventricular tachyarrhythmias ceased. Our patient recovered from his cardiac arrest without any neurological deficit. Further tests and examinations revealed no other reason for the cardiac arrest.</p> <p>Conclusion</p> <p>Diarrhea can cause life-threatening situations due to the excretion of potassium, ultimately causing cardiac arrest due to hypokalemia. Physicians treating patients with severe diarrhea should consider monitoring their electrolyte levels.</p
Presymptomatic risk assessment for chronic non-communicable diseases
The prevalence of common chronic non-communicable diseases (CNCDs) far
overshadows the prevalence of both monogenic and infectious diseases combined.
All CNCDs, also called complex genetic diseases, have a heritable genetic
component that can be used for pre-symptomatic risk assessment. Common single
nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome
currently account for a non-trivial portion of the germ-line genetic risk and
we will likely continue to identify the remaining missing heritability in the
form of rare variants, copy number variants and epigenetic modifications. Here,
we describe a novel measure for calculating the lifetime risk of a disease,
called the genetic composite index (GCI), and demonstrate its predictive value
as a clinical classifier. The GCI only considers summary statistics of the
effects of genetic variation and hence does not require the results of
large-scale studies simultaneously assessing multiple risk factors. Combining
GCI scores with environmental risk information provides an additional tool for
clinical decision-making. The GCI can be populated with heritable risk
information of any type, and thus represents a framework for CNCD
pre-symptomatic risk assessment that can be populated as additional risk
information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the
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Mucosal atrophy in collagenous colitis: a case report
<p>Abstract</p> <p>Background</p> <p>Mucosal atrophy as a potential cause of impaired colonic compliance has not yet been described as a complication in Collagenous Colitis (CC).</p> <p>Case presentation</p> <p>We present a 51-year-old female patient with a 20-year history of diarrhea and diagnosed with CC ten years prior to her presentation. We reviewed reports from three colonoscopies performed after the diagnosis. Overall 12 biopsies obtained in the last two colonoscopies were re-analyzed by two pathologists blinded to the aim of the study. Besides the typical histological findings of CC, the endoscopic appearance was normal, and no histological signs of atrophy were found during the first colonoscopy. Surprisingly, the second and third colonoscopy revealed a region of advanced segmental mucosal atrophy in the cecum with the mucosal height normalizing toward the transverse colon. This pattern of atrophy was inversely related to the pattern of sub-epithelial collagen deposition, which increased toward the rectum.</p> <p>Conclusion</p> <p>If no chance occurrence, our observation supports the idea that additional factors, probably luminal in nature, may be co-responsible for the mucosal atrophy in this case. Thus, mucosal atrophy in the proximal colon appears to be a new candidate among the growing list of rare complications associated with long standing CC.</p
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Shotgun Metaproteomics of the Human Distal Gut Microbiota
The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes
Collecting a set of psoriasis family material through a patient organisation; clinical characterisation and presence of additional disorders
BACKGROUND: The aim of the present study was to describe the clinical characteristics of a population of psoriatics sampled from a patient organisation and not from hospitals or out-patient clinics. Furthermore, we wanted to compare siblings with and without psoriasis regarding the occurrence of other diseases. METHODS: At the end of 1991, we initiated a project which aimed to study genetic factors leading to psoriasis. Firstly, we sent questionnaires to all the members of the Swedish Psoriasis Association. We then examined 1,217 individuals (570 with psoriasis) from 310 families, in their homes in the southern part of Sweden. All the available family members were examined clinically and asked about the course of the skin disease and the occurrence of other diseases. The eight hundred members of the proband generation were divided into two groups, with or without psoriasis, and their clinical features were compared. RESULTS: Most individuals in this study population had a mild form of psoriasis. The siblings with psoriasis had joint complaints significantly more frequently than their siblings without the skin disease and those with joint complaints had more widespread skin disease. Among the other studied concomitant diseases (iritis, heart or hypertension disease, endocrine disease, inflammatory bowel disease and neurological disease), we were not able to find any difference. Seventy-seven of 570 persons were found to be in remission (13.5%). Females had a mean onset 2.5 years earlier than males. We were not able to find any correlation between the extent of the skin disease and age at onset. Twice as many persons with joint complaints were found among those with psoriasis than among those without, 28% versus 13%. Almost half (48%) the psoriatics who also had joint complaints had psoriasis lesions on their nails. Endocrine disorders were found in 9% of those without any allele for Cw6, but only in 1% of those who had Cw6. In fact, none of 183 Cw6 carriers had diabetes, as compared to the population prevalence of 3–5% in Sweden. CONCLUSION: With the exception of joint complaints, persons with psoriasis, collected from a patient organisation, did not have an increased frequency of (studied) co-existing diseases
Low bone mass in microscopic colitis
<p>Abstract</p> <p>Background</p> <p>Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis.</p> <p>Aims</p> <p>The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis.</p> <p>Methods</p> <p>Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays.</p> <p>Results</p> <p>Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm<sup>2</sup>; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm<sup>2</sup>; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm<sup>2</sup>). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients.</p> <p>Conclusions</p> <p>Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.</p
Functional Studies on the IBD Susceptibility Gene IL23R Implicate Reduced Receptor Function in the Protective Genetic Variant R381Q
Genome-wide association studies (GWAS) in several populations have demonstrated significant association of the IL23R gene with IBD (Crohn's disease (CD) and ulcerative colitis (UC)) and psoriasis, suggesting that perturbation of the IL-23 signaling pathway is relevant to the pathophysiology of these diseases. One particular variant, R381Q (rs11209026), confers strong protection against development of CD. We investigated the effects of this variant in primary T cells from healthy donors carrying IL23RR381 and IL23RQ381 haplotypes. Using a proprietary anti-IL23R antibody, ELISA, flow cytometry, phosphoflow and real-time RT-PCR methods, we examined IL23R expression and STAT3 phosphorylation and activation in response to IL-23. IL23RQ381 was associated with reduced STAT3 phosphorylation upon stimulation with IL-23 and decreased number of IL-23 responsive T-cells. We also observed slightly reduced levels of proinflammatory cytokine secretion in IL23RQ381 positive donors. Our study shows conclusively that IL23RQ381 is a loss-of-function allele, further strengthening the implication from GWAS results that the IL-23 pathway is pathogenic in human disease. This data provides an explanation for the protective role of R381Q in CD and may lead to the development of improved therapeutics for autoimmune disorders like CD
Metabolomics Reveals Metabolic Biomarkers of Crohn's Disease
The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention
Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study
<p>Abstract</p> <p>Background</p> <p>Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population.</p> <p>Methods</p> <p>We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, <it>NOD2</it>, <it>IL23R</it>, <it>IRGM</it>, <it>ATG16L1</it>, <it>PTGER4</it>, <it>NKX2-3</it>, <it>IL12B</it>, <it>PTPN2</it>, <it>TNFSF15 </it>and <it>STAT3</it>, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value.</p> <p>Results</p> <p>Three <it>NOD2 </it>SNPs, two <it>IL23R </it>SNPs, and one SNP each at <it>IRGM </it>and <it>PTGER4 </it>were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16).</p> <p>Conclusions</p> <p>CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.</p
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