Prediction of type-1 diabetes : evaluation of assays for ß-cell antibodies

Type·1 diabetes mellitus is an autoimmune disease. The clinical manifestation is the end-point of a subclinical process that destroys the insulin producing B·cells in the islets of Langerhans (prediabetes). Prediabetes may last months to years and theoretically gives the unique opportunity for prevention of the disease. This requires the availability of an effective therapy and the possibility to reliably identify individuals who are eligible for such a therapy. In order to develop intervention strategies, studies on the pathogenesis of Type-1 diabetes are required. At the clinical manifestation of the disease B-cell autoimmunity has been present for years. As a consequence disease-initiating events will have disappeared and the immune response and pathophysiology of the B-cells may have changed due to the ongoing destruction process. Thus, studies of the prediabetic phase are a prerequisite. The identification of those who are at high risk to develop the disease is therefore an important key to further studies on the pathogenesis of Type-1 diabetes. In addition, clinical trials of potential prevention strategies require the development of reliable techniques to identify such individuals. Using a combination of genetic markers and autoantibodies against B-cell antigens, prediction is possible in first·degree relatives of patients with Type-1 diabetes. For relatives baring high genetic risk markers and being positive for more than one B-cell autoantibody the risk to proceed to diabetes exceeds 60%. However, the majority of new cases of Type-1 diabetes occur in the general population and it is not clear whether prediction in the general population is as efficient as in first degree relatives. This thesis aims to: • Decipher the natural course of B-cell autoantibodies and their relation to disease progression in established diabetes and prediabetes • Improve knowledge on the applicability of antibodies for the prediction of Type-1 diabetes in the general population • Improve the performance of screening by technical evaluation of assays to detect GAD· and IA2·antibodies in seru

Autism and theory of mind in interactive spaces.

How is an Interactive Media Arts practice placed to explore what is often considered a scientific field of research? This paper is a discussion on the main areas of study situating an observational PhD study on non-verbal children with autism. The author suggests that in fact an arts practice allows for more sensitive research and allows natural emergence to explore and facilitate the expression of Theory of Mind and physical consciousness

A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands

Type 1 diabetes has a substantial genetic component, with consistent evidence for a susceptibility locus in the HLA-DR/DQ region (chromosome 6p) and the insulin gene region (chromosome 11p). Genome scans have identified >18 other genomic regions that may harbor putative type 1 diabetes genes. However, evidence for most regions varies in different data sets. Given the genetic heterogeneity of type 1 diabetes, studies in homogeneous genetically isolated populations may be more successful in mapping susceptibility loci than in complex outbred populations. We describe a genome-wide search in a recently Dutch isolated population. We identified 43 patients that could be traced back to a common ancestor within 15 generations and performed a genome-wide scan using a combined linkage- and association-based approach. In addition to the HLA locus, evidence for type 1 diabetes loci was observed on chromosome 8q24 (marker D8S1128) and on chromosome 17q24 (marker D17S2059). Both the 8q and 17q localization are supported by allele-sharing at adjacent markers in affected individuals. Statistical evidence for a conserved ancestral haplotype was found for chromosome 8q24

IgE cross-reactivity measurement of cashew nut, hazelnut and peanut using a novel IMMULITE inhibition method

Tree nut-allergic individuals are often sensitised towards multiple nuts and seeds. The underlying cause behind a multi-sensitisation for cashew nut, hazelnut, peanut and birch pollen is not always clear. We investigated whether immunoglobulin E antibody (IgE) cross-reactivity between cashew nut, hazelnut and peanut proteins exists in children who are multi-allergic to these foods using a novel IMMULITE®-based inhibition methodology, and investigated which allergens might be responsible. In addition, we explored if an allergy to birch pollen might play a role in this co-sensitisation for cashew nut, hazelnut and peanut. Serum of five children with a confirmed cashew nut allergy and suffering from allergic symptoms after eating peanut and hazelnut were subjected to

Endophthalmitis after strabismus surgery: incidence and outcome in relation to age, operated eye muscle, surgical technique, scleral perforation and immune state

Purpose: Identify risk factors for endophthalmitis after strabismus surgery (EASS) and relate these to incidence and outcome. Methods: Ophthalmologists, who had operated, diagnosed or treated EASS, completed a case record form with 71 questions in six domains: Preoperative, Surgery, Perforation, Postoperative, Outcome and Experts’ opinion. To estimate the age-specific incidence per number of strabismus operations in the Netherlands during 1994-2013, the age distribution of Dutch cases was compared with the age-specific rates of strabismus surgery in the Dutch Registry of Strabismus Operations and with population data. Exploratory data analysis was performed. The immune state was evaluated in six patients. Five enucleated eyes were studied histopathologically. Results: None of the 26 patients (27 eyes with EASS) were between 9 and 65 years old, except for one patient with retinal haemorrhage followed by endophthalmitis. In the Netherlands during 1994-2013, the rate of EASS was approximately one per 11 000 strabismus operations, but one per 4300 for children aged 0–3 and one per 1000 for patients 65 and older. Endophthalmitis was diagnosed on postoperative day 1–4 in children aged 0–3. In all 15 children aged 0–5, the 16 affected eyes were phthisical, eviscerated or enucleated. The involved eye muscle had been recessed in 25 of 27 cases. It was a medial rectus in 15 of 16 children aged 0–6. It was a lateral (6), inferior (2) or medial (1) rectus in elderly. Scleral perforation went unnoticed in all children (no record in three) and in two of seven elderly (no record in two). Histopathology showed transscleral scarring compatible with scleral perforation in four patients but, in a two-year-old girl who had EASS together with a transient medial rectus palsy, the sclera underneath the former suture tract was not perforated but did contain the long posterior ciliary artery. Conclusions: Endophthalmitis after strabismus surgery (EASS) affects children and elderly, with a grave outcome in young children. It occurs after recession of the medial rectus muscle in children, and it may occur without scleral perforation. Age and perforation influence many other parameters that determine the occurrence and fulminance of EASS

Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans

Contains fulltext : 21889___.PDF (publisher's version ) (Open Access

Toward a data-driven evaluation of the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis: is it sensible to look at levels of rheumatoid factor?

OBJECTIVE Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus; based on paper patients), and finally a common sense-based approach (evaluation of the former phases). Now the individual items that make up these criteria are being evaluated. This study was undertaken to analyze the item "autoantibodies," in particular rheumatoid factor (RF) level. METHODS Three separate cohorts comprising a total of 972 patients with undifferentiated arthritis were studied for RA development (according to the 1987 American College of Rheumatology criteria) and arthritis persistence. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were compared between different levels of RF and the presence of anti-citrullinated protein antibody (ACPA). A similar comparison was made in 686 RA patients for the rate of joint destruction and achievement of sustained disease-modifying antirheumatic drug-free remission during 7 years of followup. The variation in RF levels obtained by different measurement methods in the same RF-positive sera was explored. RESULTS Compared to high RF levels, presence of ACPA had a better balance between positive LR and negative LR and between PPV and NPV for RA development. The additive value of ACPA assessment after testing for RF level was higher than vice versa. The association between high RF level and RA severity was not as strong as that between ACPA antibodies and RA severity. The RF level obtained by different methods in the same patients' sera varied considerably. CONCLUSION Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACPA positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA.Pathophysiology and treatment of rheumatic disease