Regulatory objectivity in action: Mild cognitive impairment and the collective production of uncertainty

In this paper, we investigate recent changes in the definition and approach to Alzheimer’s disease brought about by growing clinical, therapeutic and regulatory interest in the prodromal or preclinical aspects of this condition. In the last decade, there has been an increased interest in the biomolecular and epidemiological characterization of pre-clinical dementia. It is argued that early diagnosis of dementia, and particularly of Alzheimer‘s disease, will facilitate the prevention of dementing processes and lower the prevalence of the condition in the general population. The search for a diagnostic category or biomarker that would serve this purpose is an ongoing but problematic endeavour for research and clinical communities in this area. In this paper, we explore how clinical and research actors, in collaboration with regulatory institutions and pharmaceutical companies, come to frame these domains as uncertainties and how they re-deploy uncertainty in the ‘collective production’ of new diagnostic conventions and bioclinical standards. While drawing as background on ethnographic, documentary and interview data, the paper proposes an in-depth, contextual analysis of the proceedings of an international meeting organized by the Peripheral and Central Nervous System Drug Advisory Committee of the US Food and Drug Administration to discuss whether or not a particular diagnostic convention — mild cognitive impairment — exists and how best it ought to be studied. Based on this analysis we argue that the deployment of uncertainty is reflexively implicated in bioclinical collectives’ search for rules and conventions, and furthermore that the collective production of uncertainty is central to the ‘knowledge machinery’ of regulatory objectivity

Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT. (Blood. 2012;120(16):3353-3359)National Institutes of Health Intramural Research Program, National Heart, Lung, and Blood InstituteAA and Myelodysplastic Syndrome International FoundationFrance HPNFAPES

FunctionaL coLopathy: still relevant? Let’s move to irritabLe boweL syndrome.

editorial reviewedFunctionaL coLopathy: stiLL reLevant? Let's move to irritabLe boweL syndrome. summary : Irritable bowel syndrome is a functional disorder that is frequently encountered in general practice as well as in specialized consultations. Diagnostic criteria have been well established but there is currently no specific diagnostic test. The various gastroenterology societies have recently published recommendations for diagnostic and therapeutic management adapted to the pathophysiology and the availability of treatments in different countries. This article summarizes the main lines of these recommendations and in particular those of the Belgian consensus

Genetics and environment in chronic inflammatory bowel diseases

peer reviewedInflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa homeostasis have been identified. Environmental studies have been less numerous up to now and only smoking and appendectomy have been validated, as protector for ulcerative colitis, while smoking is clearly associated with an increased risk and more severe forms of Crohn's disease. An important role is also currently suspected for the intestinal flora and the dysbiosis described in inflammatory bowel disease could contribute to the triggering or the persistence of the inflammation. New therapeutic strategies are currently studied, particularly aiming at targeting immune, inflammatory or homeostatic pathways corresponding to the predisposing gene variants

Physiologie de la cellule enterochromaffin-like (ECL) dans la régulation de la sécrétion gastrique acide

Cette mise au point rappellera d'abord les grands mécanismes de la sécrétion gastrique acide en insistant sur le rôle pivot de l'histamine. Une question qui demeurait encore non résolue était de savoir quelle était la cellule fundique qui produisait de l'histamine dans les conditions physiologiques. Deux cellules seront envisagées, les mastocytes et les cellules ECL qui sont des cellules endocrines exclusivement localisées dans le fundus. Quelques arguments seront développés, dont ceux provenant de notre expérience, permettant de penser que la cellule ECL contient de l'histamine. L'article se terminera par un essai d'intégration de la cellule ECL dans le schéma de la sécrétion gastrique acide en montrant son rôle essentiel potentiel

Physiology of Enterochromaffin-Like Cells in the Regulation of Gastric Acid Secretion

peer reviewe

Long-term evolution and predictive factors of mild inflammatory bowel disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). AIM: Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. METHODS: Retrospective study of IBD patients registered in the database of the university hospital CHU of Liege, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. RESULTS: Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. CONCLUSIONS: In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC