Study of iron metabolism disturbances in an animal model of insulin resistance

The relationship between iron and insulin-resistance (IR) is documented by the positive correlation between iron stores and IR. Moreover, some patients exhibited a hepatic iron overload associated with IR (HIO-IR) but the mechanism involved in this overload is not known. Thus, we studied the iron metabolism disturbances in an animal model of IR and the influence of provoked hyperglycemia/hyperinsulinemia on plasma iron parameters. Wistar rats were fed a control or a high-fat/high-energy (HF/HE) diet. Plasma glucose, insulin, iron, transferrin and transferrin saturation (TS) were measured during intra-peritoneal glucose test tolerance (IPGTT) compared to saline. Hemogram, tissue iron concentrations and hepatic hepcidin mRNA expression were determined at the end of experiment. HF/HE rats exhibited higher body and liver weights, increased IR-index and hemoglobin concentration. Iron content was lower in the spleen of HF/HE rats and tended to decrease in the liver as compared to controls. Transferrin values were higher and these of TS lower in HF/HE group. The hepcidin mRNA was 3.5-fold lower in HF/HE rats than in controls. IPGTT had no effect on iron status parameters in both groups. As reflected by higher hemoglobin concentration, IR could increase erythropo?esis which enhances iron requirement. Iron stores and TS value decreased leading to a down-regulation of hepcidin expression which increased iron absorption. Hepcidin expression should be investigated in metabolic syndrome and hepatic iron overload associated with IR.     

Les chélateurs du fer : quand et comment les utiliser chez l’adulte ?

Iron overload can lead to tissue damage derived from free radical toxicity. Phlebotomy is the treatment of choice for treating iron overload. However, iron chelating therapy can be used if phlebotomies are impossible, mainly because of anemia. In thalassemia major, iron chelating therapy has dramatically improved life expectancy; it is also used in sickle cell disease and myelodysplastic syndromes. Desferioxamine is the gold standard of iron chelation, but parenteral administration and the burden of a daily infusion pump hinder optimal compliance. Deferiprone is orally active but should be administered three times a day. It has the advantage of removing toxic iron from myocardium, but agranulocytosis (1 %) can limit its use. Deferasirox is orally active in a single daily dose, is well tolerated but its cardiac effect is limited. Iron chelating therapy can be considered if serum ferritin is above 1000 μg/L and if liver iron concentration assessing by MRI exceeds 80 μmol/g. MRI is a very important mean to monitor cardiac iron load. If the relaxing parameter T2* is lower than 20 ms, a cardiac effective iron chelator agent or an association with deferoxamine should be used. Benefit/risk ratio should be closely evaluated, mainly in myelodysplastic syndromes.     

Mesenteric venous thrombosis. A retrospective study of 23 cases

Mesenteric venous thrombosis is uncommon. Diagnosis is difficult and much remains to be learned about clinical aspects, etiology and treatment options. PATIENTS AND METHODS: We conducted a retrospective study over 5 years concerning patients with isolated mesenteric venous thrombosis or with extension to the portal vein. RESULTS: Twenty-three patients (12 women), mean age 55 years, were included. Abdominal pain (96%), bowel obstruction (35%), fever (26%), diarrhea (17%), gastrointestinal bleeding (13%) were the most common symptoms at presentation. In 78% of patients, at least one underlying condition was identified: thrombophilia, oral contraceptive, cancer, paroxysmal nocturnal hemoglobinuria, essential thrombocythemia, intra-abdominal processes. CT scan and ultrasound diagnostic sensitivity were 89% and 57% respectively. Outcome was favorable for the 18 patients treated with anticoagulants (associated with surgery in 4 patients). Three patients with neoplasm died early. CONCLUSION: Mesenteric venous thrombosis must be kept in mind as a possible diagnosis in patients with abdominal pain. Predisposing factors are frequently associated and should be searched for. Early diagnosis, using CT scan or ultrasound, enables immediate anticoagulation and seems to improve outcome.     

Non infectious endocarditis: retrospective study (6 cases)

PURPOSE: If there is cardiac valve vegetation and the blood cultures are negatives we need to look for slow growing bacteria, fungi, Legionella pneumophilia, Bartonella henselae and quintana, Brucella melitensis and abortus, Coxiella burneti, Chlamydiae pneumoniae by serologic tests. The diagnosis of non- infectious endocarditis could be considered only if these results were negative. The main purpose of this study was to describe the clinical and echocardiographic signs of non-infectious endocarditis cases observed in two different wards. METHODS: This study was done retrospectively during a five-year period in a cardiology and an internal medicine wards. The selection criteria are: the proof of at least one cardiac valve vegetation, observed on echocardiography, negative blood cultures and negative serologic tests as described above. RESULTS: Six non-bacterial endocarditis were described. Four Libman-Sacks endocarditis, two associated with a primary antiphospholipid syndrome revealed by an acute ischemia of leg for one patient and by an eclampsia for another and the other two associated with a systemic lupus erythematous revealed by fever for one patient and by neurologic symptoms for the other. One fibroblastic endocarditis associated to an essential hypereosinophilia and one marastic endocarditis associated to a metastatic mucin-producing cancer. CONCLUSIONS: For these six cases, a complete physical examination, a CBC for hypereosinophylia, a dosage of antiphospholipid antibodies and a thoraco-abdominal CT-scan allowed the etiologic diagnosis of non infectious endocarditis. Libman Sacks endocarditis associated with an antiphospholipid syndrome is the main etiology for which a long-term anticoagulation treatment was not followed.     

Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature

To describe the main characteristics and outcome of autoimmune thrombocytopenic purpura (AITP) in patients with common variable immunodeficiency (CVID), we analyzed data from 21 patients and reviewed additional cases from the literature. To be included in this study, patients had to have CVID and a previous history of AITP with a platelet count < or = 50 x 10(9)/L at onset. A complete response to treatment was defined by a platelet count > or = 150 x 10(9)/L, and a partial response by a platelet count >50 x 10(9)/L with an increase of at least twofold the initial level. The median platelet count at AITP diagnosis was 20 x 10(9)/L (range, 2-50 x 10(9)/L). The median age at AITP diagnosis was 23 years (range, 1-51 yr), whereas the median age at CVID diagnosis was 27 years (range, 10-74 yr). CVID was diagnosed before the onset of AITP in only 4 patients (19%), 3 of whom were being treated with intravenous immunoglobulin (i.v.Ig) replacement therapy. CVID was diagnosed more than 6 months after AITP in 13 cases (62%), and the 2 conditions were diagnosed concomitantly in 4 cases. Eleven patients (52%) had at least 1 autoimmune manifestation other than AITP, among which autoimmune hemolytic anemia (7 cases) and autoimmune neutropenia (5 cases) were preeminent. Seventeen of the 21 patients (80%) received at least 1 treatment for AITP; 13 patients received corticosteroids alone and 7 (54%) achieved at least a partial response; 8 patients received i.v.Ig at 1-2 g/kg alone or in combination with steroids, leading to a short-term response rate of 50%. Four patients underwent a splenectomy (2 complete responses, 2 failures); 2 additional splenectomies were performed for associated autoimmune hemolytic anemia. With a mean follow-up of 5.6 years after the surgical procedure, none of the 6 splenectomized patients had a life-threatening infection. With a median follow-up after AITP onset of 12 years, 13/21 patients (62%) were in treatment-free remission (7 complete responses, 6 partial responses), 7 patients (23%) were in remission while on prednisone < or = 20 mg/day with or without azathioprine, and only 1 patient still had a platelet count <50 x 10(9)/L. Five patients had died at the time of the analysis; none of the deaths was related to a hemorrhage. Severe infections including 3 fatal bacterial infections and 2 opportunistic infections occurred in 6 patients during or after treatment of AITP. In conclusion, AITP, alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with CVID, and is not prevented by i.v.Ig substitutive therapy. Since AITP frequently precedes the diagnosis of CVID, testing for immunoglobulin levels should be performed in every patient diagnosed with AITP. Steroids and splenectomy seem to have the same efficacy as in idiopathic AITP, but the increased risk of severe infections must be taken into consideration.     

Successful treatment with azathioprine of relapsing Rosai-Dorfman disease of the central nervous system

Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytosis that usually presents with lymphadenopathy. Although isolated involvement of the CNS was considered to be uncommon, numerous cases have been reported in recent years. For RDD of the CNS, the treatment consists, in general, of surgery. In cases of partial resection or relapse, chemotherapy regimens, corticosteroids, and/or radiotherapy have yielded negative results. The authors describe the case of a 57-year-old man with a history of chronic Q fever who presented with aphasia and partial seizure. Computed tomography of the brain revealed a left frontotemporal lesion that was suggestive of a meningioma. The lesion was partially resected and histopathological evaluation revealed the presence of RDD. Nineteen months later, a Jacksonian seizure prompted MRI evaluation, which disclosed a local recurrence of the tumor. Computed tomography and FDG-PET demonstrated that the RDD involved no other site, but the presence of ileitis, noted on ileoscopy, led to the diagnosis of Crohn disease. Treatment with the purine analog azathioprine was initiated, leading to an objective and sustained response in both the RDD tumor and ileitis over 35 months of follow-up. This case report highlights the potential use of a purine analog in cases of relapsing RDD of the CNS and a possible common defect of macrophage regulation in RDD, Crohn disease, and Q fever.