[Show abstract][Hide abstract] ABSTRACT: Insulin resistance is a pathological condition that arises when insulin signaling is impaired, forcing β-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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Autoimmune hematological disorders include all conditions in which blood components are attacked by the immune system. The
autoimmune cytopenias are a typical example, including: autoimmune thrombocytopenic purpura, autoimmune hemolytic anemia,
Evans syndrome, and autoimmune neutropenia. Other autoimmune hematological disorders include acquired thrombotic thrombocytopenic
purpura which is linked to the presence of anti-ADAMTS 13 autoantibodies, and acquired hemophilia – due to the presence of
anticoagulation factor antibodies. All these conditions are characterized by their acute onset and often need urgent medical
attention. This chapter addresses the clinical, diagnostic, and treatment options of hematological autoimmune disorders in
the emergency setting.
KeywordsAcquired hemophilia-Anticoagulation factor autoantibodies-Autoimmune cytopenia-Autoimmune hemolytic anemia-Autoimmune neutropenia-Autoimmune thrombocytopenic purpura-Autoimmune thrombotic thrombocytopenic purpura-Autoimmunity-Emergency-Immune thrombocytopenia-Life-threatening disorders
[Show abstract][Hide abstract] ABSTRACT: 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%.
Expert Review of Hematology 04/2011; 4(2):143-51. · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leonardi and Rosa's (2010) research on the link between celiac disease and viral hepatitis (1) is well designed and fo-cuses on a very interesting topic. Several de novo or latent autoimmune disorders or diseases have been reported in cases of chronic viral hepatitis infections, especially Hepati-tis C (2). In this paper, we report 5 cases of established perni-cious anemia during chronic viral hepatitis infection. These cases were extracted from a retrospective (1996 to 2010) study of 82 cases of pernicious anemia in the University Hospital of Strasbourg, France, a tertiary reference center (personal communication in the French Congress of He-matology, Paris, December, 2010). Clinical characteristics of the 5 patients are described in table 1, particularly details on hepatitis infection, modalities of the interferon-alpha treat-ment, and data on the cobalamin deficiency related to the pernicious anemia. Data of 3 patients were previously pub-lished in the literature (3). It is important to note that, in one case, an association was found between pernicious anemia, true celiac disease, and chronic actve Hepatitis C infection. All the patients were successfully treated with regular in-tramuscular cyanocobalamin therapy (despite continuous administration of interferon-alpha in 2 cases). To the best of our knowledge, there are only a relatively small amount of cases (< 10 in our own data) documenting a relationship between symptomatic pernicious anemia and viral hepatitis infections. Our patients had established pernicious anemia with documented cobalamin deficiency (in accordance with recent criteria; (4)). They also have a clear chronic active viral hepatitis infection on liver biopsy (1 case of Hepatitis B and 4 cases of Hepatitis C). Moreover, one of our patients had a well-documented case of celiac disease with malabsorption and antitransglutamise antibodies, partially cured with nu-tritional restrictions (no gluten intake). The pathogenis (the link) of this association is not well known, but the role of the virus or of the interferon-alpha treatment as an immuno-modulatory agent is possible (5). However in our opinion, the fact that this association is exceptional led to the suspi-cion of a fortuitous association. Thus before any conclusions can be made, future studies similar to Leaonardi and Rosa (2010) are required. Nevertheless, it is important to be aware of the possibility of the association between pernicious ane-mia and chronic viral hepatitis infections because recogni-tion of this association can help prevent severe cobalamin deficiency.
[Show abstract][Hide abstract] ABSTRACT: L’hypervitaminémie B12 est une anomalie fréquente et sous-estimée.
Cliniquement, elle peut parfois s’accompagner paradoxalement de signes de carence traduisant en fait un déficit fonctionnel en rapport avec des anomalies qualitatives relatives à des défauts de captation et d’action tissulaires de la vitamine B12.
Le profil étiologique des hypervitaminémies B12 comporte majoritairement des entités pathologiques graves et pour lesquelles la précocité diagnostique est plus que déterminante au plan pronostique. Ces entités sont représentées essentiellement par les néoplasies solides, les hémopathies malignes et les hépatopathies.
Ceci rend compte de l’importance potentielle que pourrait avoir le dosage de la vitamine B12 comme marqueur précoce dans l’orientation diagnostique de ces affections.
Une approche codifiée est nécessaire afin de déterminer les indications potentielles de la recherche d’une hypervitaminémie B12 et la conduite à tenir pratique à adopter devant la découverte d’une hypervitaminémie B12.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia.
La Presse Médicale 12/2010; 39(12):e273-9. · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Our experience and the present analysis support the use of oral cobalamin therapy in clinical practice.
Expert Opinion on Pharmacotherapy 02/2010; 11(2):249-56. · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectif
Nous avons évalué l’efficacité et la tolérance de la vitamine B12 par voie orale chez des patients avec une carence en vitamine B12 de diverses causes.
Cette étude rétrospective a inclus des patients qui ont été traités par cyanocobalamine administrée par voie orale pendant au moins 3 mois, à des posologies allant de 125 à 1000 microg par jour. La concentration sérique en vitamine B12 (critère principal) et les paramètres hématologiques (critère secondaire) ont été analysés avant et après traitement et les résultats comparés entre les 2 groupes. La tolérance du traitement a été analysée.
Vingt patients avec une maldigestion des cobalamines alimentaires et 11 avec une anémie de Biermer ont été inclus. Après 3 mois de traitement, la concentration sérique de vitamine B12 a augmenté significativement chez tous les patients, en moyenne de 161,6 ± 79,3 pg/mL dans le groupe maldigestion (p < 0,00005) et de 136,7 ± 67,4 pg/mL dans le groupe des patients avec une maladie de Biermer (p < 0,0001), sans différence entre les 2 groupes. Les paramètres hématologiques ont eu tendance à se normaliser chez plus de 90 % des patients et ce indépendamment de la cause de la carence en vitamine B12. Un patient a eu une urticaire.
Nous avons confirmé l’efficacité de la vitamine B12 par voie orale comme traitement de la carence en vitamine B12 et cela quelle que soit la cause de cette carence.
Ce qui était connu•La plupart des essais cliniques ont confirmé la non-infériorité de la voie orale par rapport à la voie parentérale de la vitamine B12 au cours du syndrome de maldigestion des cobalamines alimentaires avec une normalisation des différents paramètres étudiés (vitamine B12 sérique, homocystéine, acide méthyl malonique) et des anomalies hématologiques.•Une régression des signes cliniques a été observée chez la plupart des patients.•L’efficacité de la vitamine B12 par voie orale est discutée dans la maladie de Biermer.
Ce qu’apporte l’article•La vitamine B12 administrée par voie orale a été efficace pour traiter la carence en vitamine B12.•L’efficacité a été observée quelle que soit la cause de la carence.
[Show abstract][Hide abstract] ABSTRACT: The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment.
PubMed was systematically searched for English and French articles published from January 1990 to January 2007.
Prospective randomized studies (n = 3), a systematic review by the Cochrane group (n = 1) and prospective studies in well-determined population (n = 5) provide evidence that oral cyanocobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature may not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment.
This present review confirms the previously reported efficacy of oral cyanocobalamin treatment in elderly patients.
Annales d Endocrinologie 09/2009; 70(6):455-61. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Idiosyncratic drug-induced thrombocytopenia is a relatively rare and potentially serious side-effect in its moderate and profound forms (platelet count less than 100 x 10(9)L). It may be of central or peripheral mechanism, with consumption or immunological destruction. The main incriminated molecules are heparins, quinidine, sulfonamides and gold salts. Hemorrhagic manifestations are the rule and their severity is related to the level of thrombocytopenia and the involved molecule. Heparin-induced thrombocytopenia is more often associated with thrombotic events. Diagnosis relies on medical history and clinical criteria, which also establish the level of imputability. The role of serological tests is not yet clear but seems to be particularly interesting in difficult diagnostic situations and in heparin-induced thrombocytopenia. The treatment is based on the discontinuation of the incriminated drug and on supportive measures that depend on the severity of the clinical features.
La Revue de Médecine Interne 05/2009; 30(10):866-71. · 0.90 Impact Factor