Metabolic inflammation: connecting obesity and insulin resistance.

Insulin resistance is a pathological condition that arises when insulin signaling is impaired, forcing ß-cells to produce more insulin in order to cope with body demands and to maintain glucose homeostasis. When the pancreas is no more able to support an appropriate insulin secretion, insulin resistance becomes decompensated and hyperglycemia is detected. One of the mechanisms leading to insulin resistance is low-grade inflammation that involves a number of protagonists such as inflammatory cytokines, lipids and their metabolites, reactive oxygen species (ROS), hypoxia and endoplasmic reticulum stress, and changes in gut microbiota profiles. We review here the molecular aspects of metabolic inflammation converging to insulin resistance and secondarily to type 2 diabetes. We also discuss the place of high-sensitivity C-reactive protein (hsCRP) in the assessment of metabolic inflammation and potential therapeutic interventions aimed to impede inflammation and therefore prevent insulin resistance.

Gender-related analysis of the clinical presentation, treatment response and outcome in patients with immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) frequently occurs in young adults, particularly women in their third or fourth decade. The female predominance suggests that sex hormones may play a role in the different aspects of ITP. In this paper, we report a gender-related analysis of patients with ITP, specifically examining the clinical manifestations, responses to treatment and overall outcomes of the patients. METHODS: We included patients with "ITP" attending the departments of onco-hematology or internal medicine B (university hospital of Strasbourg, France) between 1990 and December 2010 The gender-related analysis was retrospective. RESULTS: We studied in 225 consecutive cases of established ITP with a follow-up period of 1.7 to 112 months The mean age of the patients was 44 years; 156 patients were female. The analysis revealed no significant statistical differences regarding patient characteristics between the female and male groups, with the exception of the following characteristics: the bleeding score, which altered in the presence of meno- and/or metrorrhagia and hematuria in female patients (P=0.03); the presence of anemia (P=0.04); and the detection of antinuclear and/or antiphospholipid antibodies (P=0.02). During the follow-up, no statistically significant difference was found regarding outcome or treatment response in relation to gender among these 225 patients (all P>0.05). DISCUSSION: Gender does not appear to affect the manifestation of immune thrombocytopenia, the outcome or response to treatment. However, further large-scale randomized trials are needed to confirm these findings.

[Hypervitaminemia B12 (high level of cobalamin): physiopathology, role and interest in clinical practice]. / Hypervitaminémie B12 : physiopathologie et intérêt en pratique clinique.

Hypervitaminemia B12 or high serum level of cobalamin B12 is a frequent and clinical underestimated abnormality. Clinically, it can be sometimes paradoxically accompanied by signs of deficiency reflecting a functional deficit in relation to qualitative abnormalities related to defects in tissue uptake and action of vitamin B12. Etiological profile of hypervitaminemias B12 has mostly serious disease entities and for which early diagnosis is crucial to the plan rather than prognostic. These entities are represented mainly by solid malignancies, hematological malignancies and liver diseases. This reflects the potential significance that may have the dosage of vitamin B12 as an early marker of diagnosis of these diseases. Codified approach is needed to determine the potential indications of the search for a hypervitaminemia B12 and practice what to do to pass before the discovery of a high serum level of cobalamin.

Clinical presentation and management of drug-induced agranulocytosis.

OBJECTIVE: In this article, we report and discuss the clinical presentation and management of idiosyncratic drug-induced agranulocytosis (neutrophil count <0.5 × 10(9)/l). RESULTS/CONCLUSIONS: Idiosyncratic drug-induced agranulocytosis remains a potentially serious adverse event owing to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia and septic shock in approximately two-thirds of all hospitalized patients. However, several prognostic factors have recently been identified that may be helpful in practice to identify 'susceptible' patients. Old age (>65 years), septicemia or shock, metabolic disorders such as renal failure and a neutrophil count below 0.1 × 10(9)/l are currently consensually accepted as poor prognostic factors. In this potentially life-threatening disorder, modern management with broad-spectrum antibiotics and hematopoietic growth factors (particularly granulocyte colony-stimulating factor) is likely to improve prognosis. Thus, with appropriate management, the mortality rate from idiosyncratic drug-induced agranulocytosis is currently approximately 5%.

[Oral vitamin B12: Efficacy and safety data in 31 patients with pernicious anemia and food-cobalamin malabsorption]. / Efficacité et tolérance de la vitamine B12 par voie orale chez 31 patients avec une maladie de Biermer ou une maldigestion des cobalamines alimentaires.

OBJECTIVE: The aim of this study is to validate the efficacy and safety of oral cobalamin therapy in the treatment of cobalamin deficiency related to various causes. PATIENT AND METHOD: It's a retrospective study, including 31 patients with documented cobalamin deficiency related to food-cobalamin malabsorption (n=20) and pernicious anemia (n=11). These patients were treated at least for 3 months with oral cyanocobalamin, between 125 to 1000microg per day. Serum cobalamin levels and hematological parameters were compared before and after the therapy and in relation with the nature of cobalamin deficiency. Safety data were also recorded. RESULTS: After 3 months of therapy, the serum cobalamin levels have significantly increased in all the patients, with a mean of +161.6±79.3pg/mL in the food-cobalamin malabsorption group (P<0,00005) and +136.7±67.4pg/mL in the pernicious anemia group (P<0,0001). Hematological parameters have been normalized in 90 % of the patients, independently of the cause of the cobalamin deficiency. Only 1 patient presented an urticarial reaction. CONCLUSION: This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia.

Efficacy of oral cobalamin (vitamin B12) therapy.

IMPORTANCE OF THE FIELD: Cobalamin (vitamin B12) deficiency is particularly common in the elderly (> 15%). Management of cobalamin deficiency with cobalamin injections is well codified at present, but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption. AREAS COVERED IN THIS REVIEW: The objective of this review is to evaluate the efficacy of oral cobalamin treatment in elderly patients. To reach this objective, PubMed data were systematically searched for English and French articles published from January 1990 to July 2008. Data from our research group on cobalamin deficiency (Groupe d'Etude des CAREnce vitamine B12 - CARE B12) were also analyzed. WHAT THE READER WILL GAIN: Three prospective randomized studies, a systematic review by the Cochrane group and five prospective cohort studies were found and provide evidence that oral cobalamin treatment may adequately treat cobalamin deficiency. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume and reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections. TAKE HOME MESSAGE: Our experience and the present analysis support the use of oral cobalamin therapy in clinical practice.

[Food-cobalamin syndrome]. / Syndrome de non-dissociation de la vitamine B12 de ses proteines porteuses ou de maldigestion des cobalamines alimentaires.

Food-cobalamin malabsorption is a new well-characterized syndrome. In association with pernicious anemia, it is the leading etiology of cobalamin deficiency in adult, especially in elderly patient. Currently, it is an exclusion diagnosis that requires a well-codified clinical strategy for diagnosis. There are several causes of food-cobalamin malabsorption, mainly gastric disorders and drugs (metformin and anti-acid drugs). Current treatment modality includes oral cobalamin administration with lower doses than in pernicious anemia. Studies are in the way to better characterize the food-cobalamin malabsorption in a clinical practice perspective and to validate the usefulness of oral cobalamin therapy.