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OBJECTIVE: The aim of the study was to determine the respective impact of thyroxine and growth hormone on in vivo skeletal mitochondrial function assessed via post exercise phosphocreatine recovery. DESIGN: The hind leg muscles of 32 hypophysectomized rats were investigated using (31)P nuclear magnetic resonance spectroscopy at rest and during the recovery period following a non tetanic stimulation of the sciatic nerve. Each rat was supplemented with hydrocortisone and was randomly assigned to one of the 4 groups: the group Hx was maintained in hypopituitarism., the group HxT was treated with 1 µg/100g/day of thyroxine (T4), the group HxG with 0.2 IU/kg/day of recombinant human GH (rGH) and the group HxGT by both thyroxine and rGH. Inorganic phosphate (Pi), phosphocreatine (PCr) and ATP were directly measured on the spectra, permitting the calculation of the phosphorylation potential (PP). RESULTS: At rest, the rats treated with rGH or T4 exhibited higher PCr levels than rats Hx. The recovery rates of PCr and PP were higher in rats treated with T4 than in T4-deprivated rats, suggesting improved mitochondrial function. The rats treated by both T4 and rGH showed higher PCr and PP recovery than those maintained in hypopituitarism or treated with T4 or rGH alone. CONCLUSIONS: The study demonstrates that in contrast to T4, GH given alone in hypophysectomized rats does not improve in vivo mitochondrial oxidative metabolism. Growth hormone potentiates T4 effects on oxidative metabolism.

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PURPOSE: Uveitis may rarely reveal sarcoidosis in Caucasian patients. Our objective was to analyze the clinical manifestations, and the outcome in a group of patients in whom uveitis was the presenting manifestation of sarcoidosis. METHODS: Retrospective study including 23 patients (mean age: 50.3±14.5 years) diagnosed with sarcoidosis after an episode of uveitis. Granulomatous lesions were documented in 14 patients. RESULTS: Ophthalmological examination revealed anterior uveitis (n=5), intermediate uveitis (n=2), posterior uveitis (n=25) and panuveitis (n=11). Ocular inflammation was bilateral in 16 patients (69,6%), typical aspects of granulomatous uveitis were found in only 16 eyes over 39 (41%), posterior uveitis was found in 18 eyes (46.2%), with an averaged visual acuity of 5/10. Macular oedema was noted in five patients. Suggestive signs of ocular sarcoidosis were present in 43% of the patients. Stage 1 or 2 pulmonary involvement (n=22), musculoskeletal (22%), skin (13%), or spleen (9%) involvements were the most common findings. Oral corticosteroids were necessary in 91.3% of the patients, immunosuppressive agents in 26.1%, with a prolonged treatment greater than two years in 58%. The visual prognosis was good, with visual acuity greater than 6/10 in 96% of the cases if the ocular inflammation spared retina and choroid. However, a visual acuity less than 6/10 was observed in 44% of the cases when the posterior segment was involved. CONCLUSION: Sarcoidosis may be revealed by an intraocular inflammation, with typical patterns in only 43% of the cases. Sarcoidosis should therefore be included in the differential diagnosis of every uveitis. Oral corticosteroids are required in almost all cases, owing to ocular involvement rather than visceral involvement.

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OBJECTIVES: Older people have an increased risk of low molecular weight heparin accumulation leading to an increased bleeding risk. The objective of this study was to assess whether reduced glomerular filtration rate (GFR), estimated by the Cockcroft-Gault or modification of the diet in renal disease (MDRD) equations, indicates drug accumulation by increased anti-Xa levels in older subjects receiving prophylactic enoxaparin treatment. DESIGN: Cohort study. SETTING: Acute geriatric units in Nancy Hospital. PARTICIPANTS: Ninety-two consenting consecutive patients, 65 and older, confined to bed for an acute medical condition requiring enoxaparin for prevention of venous thromboembolism, and hospitalized for at least six days were enrolled. MEASUREMENTS: Serum creatinine and peak plasma anti-Xa levels 3 to 4 hours after the daily injection of enoxaparin were measured at days 3, 6, 9 and 12 (first dose of enoxaparin at day one). Analyses of variance for repeated measures were used to evaluate significant predictors of peak anti-Xa activity in univariate and multivariate analyses. RESULTS: A significant correlation was observed between anti-Xa activity and GFR estimated with the Cockcroft formula r=0.43. Following univariate analysis, the three factors associated with higher anti-Xa levels were a lower Cockcroft-Gault GFR (p=0.0002), female gender (p=0.0003) and a lower bodyweight (p<.0001). No significant association between anti-Xa levels and MDRD GFR (p=0.33) was observed. Following multivariate analysis, female gender (p=0.02), bodyweight (p=0.04) and Cockcroft GFR (p=0.05) remained independent determinants of anti-Xa levels. CONCLUSION: In hospitalized patients older than 65 years old, the Cockcroft-Gault equation, in contrast to the MDRD equation, is able to predict the risk of higher anti-Xa levels.

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PURPOSE: Leukocytosis is considered as an argument for infection. We have compared leukocytosis with the other data available with the white blood cell count. METHODS: White blood cell counts obtained from 187 patients (age: 18 to 81 years), admitted to an emergency room for abdominal pain, were analysed using an automate (Bayer Technicon H2, Dublin, Ireland), and compared with matched healthy subjects. The patients were classified into two groups: diseases of the biliary or of the urinary tract, and subsequently in two subgroups: infectious diseases (angiocholitis, cholecystis, pyelonephritis) or non-infectious diseases (hepatic and nephritic colic). RESULTS: Leukocytes and neutrophils were significantly increased, and eosinophils significantly decreased in all subjects by comparison with controls. These abnormalities were more important in infected patients. Lymphocytes were significantly decreased in infectious disease. For predicting infection, sensitivity and specificity of leukocytosis (> 1,000/mm3) were respectively 66% and 56%, while that of eosinopenia (< 100/mm3) were respectively 91% and 38%, and that of lymphopenia (< 1,200/mm3) respectively 58% and 73%. The probability of infection was less than 3% when neutrophils were less than 7,000/mm3, and eosinophils and lymphocytes respectively more than 100/mm3 and 1,200/mm3. CONCLUSION: This study shows that leukocytosis, eosinopenia or lymphopenia are poor indicators of infection, when considered alone or in combination. However, eosinopenia and lymphopenia appear as better criteria of infection than leukocytosis. A detailed analysis of the white blood cell count allows the exclusion of infection with an acceptable risk of error.

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INTRODUCTION: The clinical expression of Lyme disease is highly variable. If a patient presents clinical findings consistent with a systemic Lyme borreliosis, this disease must be considered in an endemic area because of its favorable outcome with adequate treatment. EXEGESIS: The authors report and discuss the case of a patient with an unusual history of dilated cardiomyopathy and supraventricular fibrillation followed by bilateral panuveitis. Enzyme-linked immunosorbent assay and Western blot were positive for Borrelia burgdorferi antigens. The diagnosis of Lyme disease was made after other infectious, inflammatory and autoimmune disorders were excluded by clinical, instrumental and biological investigations. The treatment by ceftriaxone and amoxicillin resolved the ophthalmologic manifestations and improved the cardiac condition. CONCLUSION: This report underlines the possibility of an unusual presentation of Lyme disease. Ophthalmologic and cardiac involvement should be known by clinicians.

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INTRODUCTION: Pancoast's syndrome is generally due to superior sulcus tumors, generally bronchial cancer. In rare cases, other causes are found, but these are potentially curable. CASE-REPORT: A 78-year old woman with a long history of tobacco intake presented with Pancoast's syndrome in the form of a locally invasive left apical lung mass. Despite her advanced age and the diagnosis of the high probability of lung cancer, a transparietal biopsy procedure was nevertheless performed, with the subsequent diagnosis of primary malignant pulmonary lymphoma. The patient was satisfactorily treated by combined chemotherapy. CONCLUSION: The present study has shown that malignant non-Hodgkin lymphomas should be considered in the etiology of the disease, and as a rare but potentially treatable cause of Pancoast's syndrome.

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We report here that antiinsulin receptor (anti-IR) autoantibodies (AIRs) from a newly diagnosed patient with type B syndrome of insulin resistance induced cellular resistance not only to insulin but also to insulin-like growth factor I (IGF-I) for the stimulation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase activities and of glycogen and DNA syntheses. The molecular mechanisms of this dual resistance were investigated. Patient AIRs bound the IR at the insulin-binding site and caused insulin resistance at the IR level by inducing a 50% decrease in cell surface IRs and a severe defect in the tyrosine kinase activity of the residual IRs, manifested by a loss of insulin-stimulated IR autophosphorylation and IR substrate-1 (IRS-1)/IRS-2 phosphorylation. In contrast, cell resistance to IGF-I occurred at a step distal to IGF-I receptors (IGF-IRs), as AIRs altered neither IGF-I binding nor IGF-I-induced IGF-IR autophosphorylation, but inhibited the ability of IGF-IRs to mediate tyrosine phosphorylation of IRS-1 and IRS-2 in response to IGF-I. Coimmunoprecipitation assays showed that in AIR-treated cells, IRs, but not IGF-IRs, were constitutively associated with IRS-1 and IRS-2, strongly suggesting that AIR-desensitized IRs impeded IGF-I action by sequestering IRS-1 and IRS-2. Accordingly, AIRs had no effect on the stimulation of mitogen-activated protein kinase activity or DNA synthesis by vanadyl sulfate, FCS, epidermal growth factor, or platelet-derived growth factor, all of which activate signaling pathways independent of IRS-1/IRS-2. Thus, AIRs induced cell resistance to both insulin and IGF-I through a novel mechanism involving a constitutive and stable association of IRS-1 and IRS-2 with the IR.

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We report the case of a 44-year-old woman, who experienced acute back pains, leg paraesthesia, and diplopia. Analysis of the cerebrospinal fluid revealed, in addition to increased protein and decreased glucose levels, an elevated number of large atypical cells, resembling lymphoma cells. Magnetic resonance imaging of the brain and spine was normal. High levels of antibodies against Borrelia burgdorferi were found in both serum and cerebrospinal fluid. The patient completely recovered with ceftriaxone therapy.

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We report the effects of enzyme replacement therapy in a patient with Gaucher's disease associated with a monoclonal gammopathy. Alglucerase induces a linear decline in immunoglobulin and beta 2-microglobulin levels. This observation suggests that this treatment decreases the chronic antigenic stimulation commonly found in Gaucher's disease.

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A diagnosis of sarcoidosis was evoked in a 61-year-old man on clinical and histologic bases. Nevertheless, a bile duct carcinoma was disclosed in association with the discovery of generalized sarcoid-like granulomas. This is only the third time that such an association has been described. HLA-B8, DR3, and DRw52 antigens were found, suggesting that altered immunologic mechanisms could play a role in the pathogenesis of this sarcoid-like reaction.

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