Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis.

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNFalpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. METHODS: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. RESULTS: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. CONCLUSION: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. ClinicalTrials.gov number, NCT00639821.

ECG abnormalities in predicting secondary cerebral ischemia after subarachnoid haemorrhage.

BACKGROUND: Electrocardiographic (ECG) abnormalities frequently occur after subarachnoid haemorrhage (SAH), and have been linked with poor outcome. The pathogenesis behind this relation is unclear. We hypothesized that cardiac dysfunction may contribute to the development of delayed cerebral ischemia (DCI) and investigated if electrocardiographic repolarization abnormalities on admission, representing this cardiac dysfunction, are related to DCI. We also assessed the additional value of ECG characteristics to establish prognosticators for clinical outcome (WFNS, age and Hijdra score). METHOD: In a series of 121 consecutive patients with aneurysmal SAH we related individual repolarization-like ECG changes (ST and T-wave changes, QTc prolongation, a U-wave) to the occurrence of DCI by means of Cox proportional hazard modelling and to poor outcome (death or dependence) with logistic regression analysis. We used ROC curves to assess the additional prognostic value of the most important ECG characteristics to established prognosticators. FINDINGS: Only ST segment depression had a statistically significant relationship with the occurrence of DCI (HR 2.4 [95%CI 1.2-4.9]) in univariate analysis. In a similar analysis ST-elevation (OR 4.9; [95%CI 0.99-24.0]), ST-depression (OR 10.6; [95%CI 2.3-48.8]), T-wave inversion (OR 2.5; [95%CI 1.1-5.5]) and ischemic like ECG abnormalities (OR 8.3; [95%CI 3.0-22.2]) were significantly related to poor outcome. In multivariate models with extension of these ECG characteristics for establishing prognosticators the AUC of the ROC improved from 0.81 to 0.84. CONCLUSIONS: ECG abnormalities did not contribute to the prediction of DCI and have limited value in prognosticating poor outcome. The occurrence of DCI is not the explanation of this relationship between ECG characteristics and outcome.

[The combination of a fused tooth and a supernumerary central incisor: a possible treatment plan]. / Het samen voorkomen van een dubbeltand en een boventallig gebitselement. Een mogelijke behandeling.

An 8-year old boy was referred to the orthodontic department because of a fused tooth. The clinical and radiological examination showed that - besides the double tooth at the region of the 21 - there was a normal tooth 22 in eruption as well. Moreover a still impacted supernumerary tooth was present in the right upper front region. The treatment included the extraction of the fused tooth and an autotransplantation of the supernumerary tooth to the extraction site of the fused tooth. During the follow-up period the pulp showed a progressive obliteration starting at the crown level with a conservation of the vitality. Apexification of the root of the transplanted tooth proceeded successfully. Furthermore a review of the literature is given in this article on the aetiology and treatment of fused teeth and on the application of autotransplantation.

[Deontology in generalists-specialists relations in domestic emergencies]. / Déontologie des relations généralistes-spécialistes dans les urgences à domicile.

The deontological rules defining the relations between the general practitioners and specialists about domestic emergencies are clearly exposed in the code edited by the National Medical Council of Belgium. Ethical particularities exist. During an emergency situation, the patient could lose his freedom as well as his autonomy and might become a technical subject rather than an ethical person. The ethical values are in opposition with a medical practice trying to be more and more efficient with as a corollary, the necessity to have a full and permanent access to personal medical data.

[Clinical examination of the shoulder and diagnostic maneuvers]. / Examen clinique de l'épaule et manoeuvres diagnostiques.

The authors review in this article the anamnestic and examination steps of a patient suffering from chronic shoulder pain. They first remind the reader of the muscles intervening in the different shoulder's movements and then go over to the systematic review of the information disclosed by the disorders of the shoulder's motion, whether passively actively or against resistance. They describe the most important diagnosis tests. They finally describe an examination strategy that makes it possible to take a rational clinical decision.

Safe abortions in an illegal context: perceptions from service providers in Belgium.

Until April 1990 abortion was illegal in Belgium all circumstances. However, a small group of health professionals had long provided high-quality abortion services in outpatient facilities and in hospitals. This study is a qualitative analysis of perceptions among providers of safe abortion in Belgium before and after it was made legal there. The providers' personal, psychological, and ethical reactions to abortion are investigated, as well as their opinions on how their activities should be organized in order to minimize problems. Standardized questionnaires with closed and open questions were used; 143 questionnaires were completed. Emotional reactions were reported as being the most difficult aspects of practicing abortion. The experience of Belgian practitioners is of value for health professionals working in a legally restricted setting who are willing to assume some judicial risks to facilitate legal change while demonstrating the public health utility of low-cost, safe abortion.

PIP: Until April 1990, abortion was illegal in Belgium; still, in 1982, researchers estimated that 13,400-15,900 abortions were performed each year in public and private hospitals, abortion clinics, and family planning and abortion centers in Brussels and Wallonia. Recent estimates indicate that around 60% of abortions are performed in outpatient facilities, 32% in hospitals, and about 8% in private clinics in Belgium. The providers' personal, psychological, and ethical reactions to abortion were investigated in Belgium before and after abortion was made legal. 143 standardized questionnaires were completed: 86 by women and 57 by men. Nearly half of the respondents were physicians. The questionnaires covered aspects of the provision of medical abortion: 1) providers' objective reactions to the organization of services; 2) providers' subjective reactions to abortion service, including self-image, perception of legal restrictions, perception of clients attitudes, personal values, personal motivations, and feelings about their own role in the practice. Many of those who had decided to work in abortion services initially considered doing so to be a normal part of their job to help women cope with unwanted pregnancies. Nearly two-thirds of the respondents expressed a negative emotional reaction to requests for repeat abortions; one-third were accepting or neutral. 70% of physicians appeared to be emotionally affected by repeat abortions compared to 47% of nonphysicians. The providers believed that various factors affect the quality of abortion services, as reported by 109 providers, including the high number of abortions performed (reported by 36% of providers in hospitals and 23% in outpatient clinics); a high turnover of personnel (22% and 41%, respectively); lack of staff collaboration (20% and 11%); and the legal situation (4% and 8%). 95% of all 143 respondents expressed the view that conscientious objection to performing abortion is legitimate.