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Biomedical subjects

C Broussolle

Publications and source records attributed to C Broussolle.

At least 37 records · Page 2Linked to original sources

[Hepatitis C virus infection and thyroid diseases].

INTRODUCTION: The combination of hepatitis C virus (HCV) infection and thyroid diseases raises several issues that are the prevalence of thyroid autoimmunity in patients with chronic hepatitis C, the prevalence of HCV infection in patients with autoimmune thyroid diseases, and the effects of interferon alpha treatment on thyroid function in chronic HCV hepatitis. CURRENT KNOWLEDGE AND KEY POINTS: The prevalence of anti-thyroid auto-antibodies ranges from 4.6 to 15% in HCV infection, which is considered as significant by various authors. Results have to be interpreted according to the following: the type of auto-antibodies detected, the age, sex, ethnic origin of the population studied, and characteristics of the control population. Recent data are suggestive of a high prevalence of anti-thyroid auto-antibodies in females with HCV infection. An increased prevalence of HCV infection in patients with Hashimoto's thyroiditis is not confirmed. During treatment of chronic hepatitis C, interferon alpha induces thyroid dysfunctions (3 to 15% of the cases) with various clinical presentations. Hypothyroidism is more common (two out of three cases) than hyperthyroidism (one out of three cases). Hyperthyroidism followed by hypothyroidism has also been described. Clinical symptoms vary, ranging from subclinical to severe manifestations. Thyroid dysfunction may be delayed after discontinuation of the interferon treatment. Hypothyroidism is easily cured by L-thyroxine replacement therapy when necessary, and regression may be observed following discontinuation of interferon treatment. Each case of hyperthyroidism has to be precisely evaluated. Development of anti-thyroid antibodies or an increase in anti-thyroid antibodies titers is often observed during interferon alpha treatment, thus suggesting the existence of immunological mechanisms at the origin of thyroid dysfunction. Furthermore, interferon would directly act on iodine. FUTURE PROSPECTS AND PROJECTS: Clinical studies are still necessary to better clarify the links between HCV infection and thyroid autoimmunity, and to determine risk factors for the development of thyroid dysfunction during interferon alpha therapy. The effects of HCV and interferon alpha on thyroid autoimmunity and function have to be investigated in basic research.

Adult↗

Feasibility of intraperitoneal insulin therapy with programmable implantable pumps in IDDM. A multicenter study. The EVADIAC Study Group. Evaluation dans le Diabète du Traitement par Implants Actifs.

OBJECTIVE: To report the overall French experience, obtained through the collaboration of seven centers (EVADIAC [Evaluation dans le Diabète du Traitement par Implants Actifs] register), on the safety, feasibility, and efficacy of intraperitoneal insulin therapy by programmable implantable pumps, using three different devices. RESEARCH DESIGN AND METHODS: This is a multicenter prospective study involving 224 type I diabetic patients implanted with a programmable implantable pump (cumulative follow-up: 353 patient-years; mean duration: 1.5 +/- 0.9 years [mean +/- SD]. The Infusaid and the Promedos devices are equipped with a side port and refilled with U100 insulin (Hoechst 21 PH); the Minimed pump is not equipped with a side port and is refilled with U400 insulin (Hoechst 21 PH). Metabolic data and adverse events were recorded in a central register run by EVADIAC. RESULTS: A total of 29 local pump-pocket events (8/100 patient-years) and 9 pump failures (2.5/100 patient-years) occurred. The major technical problems were 1) pump flow rate reduction related to insulin aggregates, reversible after alkaline rinsing of the pump, and 2) 47 catheter obstructions requiring laparoscopic or conventional surgery. Pump therapy was abandoned in only 11 patients. HbA1c (7.4 +/- 1.8 vs. 6.8 +/- 1.0%, P < 0.001), mean glycemia (8.7 +/- 1.5 vs. 7.8 +/- 1.0 mmol/l, P < 0.001), and blood glucose SDs (3.8 +/- 0.8 vs. 3.3 +/- 0.8 mol/l, P < 0.001) decreased significantly after 6 months and remained lower than baseline thereafter. CONCLUSIONS: Intraperitoneal insulin infusion using an implantable programmable pump is a feasible and relatively safe technique that may improve metabolic control and glycemic stability. Long-term studies, however, are needed to demonstrate whether or not the improvement in glycemic control could be sustained for several years.

Adult↗

[Hyperthyroidism at elevated thyreostimulin. A case with pituitary resistance to thyroid hormones].

Simultaneous elevation of thyreostimulin and thyroid hormones values, when associated with clinical hyperthyroidism, raises a dual problem of diagnosis and treatment. We report a case of hyperthyroidism with elevated thyreostimulin in a young adult man. The values of free triiodothyronin and free thyroxin were elevated and the thyroxin binding globulin was normal. A normal pituitary tomodensitometry, the normal values of the alpha sub-unit of thyreostimulin and the dynamic tests of thyreostimulin secretion allowed us to rule out the hypothesis of a pituitary adenoma. Non-tumoral inappropriate secretions of thyreostimulin are at present regarded as syndromes of resistance to thyroid hormones. Their biological translation is a simultaneous elevation of thyreostimulin and thyroid hormones. Peripheral resistance, which is rarely complete, finds its expression in clinical hyperthyroidism or in normal clinical condition, whereas pituitary resistance, which causes the lack of feedback on the secretion of thyreostimulin expresses itself by clinical hyperthyroidism, sometimes with goitre owing to the trophic action of thyreostimulin on the thyroid. Generalized syndromes of resistance are the most common. Our patient had a selective pituitary resistance to thyroid hormones and less than thirty cases are reported in the literature. Treatment with a beta-blocker remains indicated when facing clinical evidence for hyperthyroidism and oral triiodothyronin seems to be able to slow down the inappropriate secretion of thyreostimulin. Regarding our patient who experienced a clinical and biological relapse after the stopping of the treatment, we join many authors who recommend a prolonged treatment.

Adult↗

French multicentre experience of implantable insulin pumps. The EVADIAC Study Group. Evaluation of Active Implants in Diabetes Society.

Limitations of intensive diabetes treatment with subcutaneous insulin include achievement of only near-normoglycaemia and increased risk of hypoglycaemia. Programmable implantable pumps permit variable rates of intraperitoneal insulin infusion. The French experience represents 224 type I adult diabetic patients followed up for 353 patient-years in seven centres. Compared with pre-implantation values with intensive subcutaneous insulin, glycaemic control was significantly improved with implantable pumps: glycosylated haemoglobin fell from 7.4 (1.8)% to 6.8 (1.0)% at 6 months (mean, SD, p < 0.001). The incidence of severe episodes of hypoglycaemia decreased from 15.2 to 2.5 per 100 patient-years (p < 0.001). Intraperitoneal insulin delivery with implantable pumps improved the risk-benefit ratio of intensive insulin.

Adolescent↗

[Sleep apnea syndrome in obese patients: are there any predictive factors ?].

The aim of this study was to determine whether clinical, spirometric, or arterial blood gas data could predict sleep apnea syndrome (SAS) among obese patients with at least one functional complaint. Eighty three obese patients, 46 males and 37 females, aged 53.2 +/- 13.7 years, with a body mass index (BMI) above 30 kg/m2 were investigated with: clinical questionnaire; pulmonary function tests; arterial blood gas measurements; nocturnal monitoring of oronasal airflow, thoracic and abdominal movements, and arterial oxygen saturation. Thirty five patients (42.2%) had a SAS, 18 (26.7%) had nocturnal oxygen desaturations, and 30 (36.1%) had a normal nocturnal monitoring. There were 63% males in the SAS group and 32% in the group without SAS (P < 0.01). Age, weight, frequency of systemic hypertension, frequency of each clinical symptom, spirometric and arterial blood gas data were identical in the two groups. In conclusion, rate of SAS is very high in obese patients presenting a BMI above 30 and at least one functional complaint. No predictive test is identified.

Adult↗

Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans.

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.

3-Hydroxybutyric Acid↗

Effects of D-beta-hydroxybutyrate and long- and medium-chain triglycerides on leucine metabolism in humans.

Ketone bodies and/or fatty acids might play a protein-sparing role during prolonged fasting or parenteral nutrition. To assess this problem, we studied whole body leucine metabolism, using L-[1-13C]leucine in normal postabsorptive volunteers who received either long-chain triglycerides (LCT, 0.15 g.kg-1.h-1, 6 subjects), a 50-50 mixture of medium-chain triglycerides (MCT) and LCT (0.15 g.kg-1.h-1, 6 subjects), D-beta-hydroxybutyrate (540 mumol.kg-1.h-1, 6 subjects), or saline (4 subjects). Leucine concentration decreased only with MCT-LCT. Leucine flux decreased by 10-20% from basal in all groups. Leucine oxidation, which was corrected for the contribution to 13CO2 of the 13C natural abundance of the infused substrates, decreased during LCT infusion (0.31 +/- 0.02 to 0.24 +/- 0.01 mumol.kg-1.min-1, P less than 0.01), but was unaffected by MCT-LCT (despite plasma free fatty acid levels similar to those obtained with LCT), D-beta-hydroxybutyrate, or saline infusion. Therefore, 1) the effect of fatty acids on amino acid oxidation is not mediated by ketone bodies, 2) it depends on the fatty acid chain length, 3) long-chain fatty acids but not medium-chain fatty acids could play a protein-sparing role during parenteral nutrition.

3-Hydroxybutyric Acid↗

Evaluation of the fructosamine test in obesity: consequences for the assessment of past glycemic control in diabetes.

The effect of obesity in diabetic and nondiabetic states on serum fructosamine levels, as measured by the nitro blue tetrazolium reduction method, was investigated. In 26 nondiabetic obese subjects, the mean (SD) fructosamine (1.78 +/- 0.16 mmol/L) and protein corrected fructosamine concentrations (25.7 +/- 2.5 mumol/g) were significantly lower than in nondiabetic lean control subjects (2.06 +/- 0.18 mmol/L and 30.5 +/- 2.5 mumol/g, respectively; p less than 0.01). Hemoglobin A1C, blood glucose and serum protein concentrations were normal in obese subjects. Interference from hypertriglyceridemia, hemolysis, or drugs was excluded. In diabetic subjects, fructosamine correlated with hemoglobin A1C, but the least-squares regression lines were different in 16 nonobese and in 19 obese patients, so that for the same hemoglobin A1C value, fructosamine level was 16% lower in obese compared to nonobese diabetic subjects. In vitro studies showed a significant decrease in 14C-glucose incorporation in serum proteins of obese nondiabetic subjects compared to control subjects. Similarly, the rate of formation of fructosamine in sera of obese nondiabetic subjects incubated with 12 mmol/L and 30 mmol/L glucose concentrations was slower than in sera of control subjects. In conclusion, fructosamine is underestimated in obesity, both in diabetic and nondiabetic patients, and its validity as an index of glycemic control may be impaired in obese subjects. This decrease is due to an alteration in the glycation process itself.

Adult↗

Regulation of insulin synthesis in an insulin-producing cell line (RINm5F): long-term experiments.

The insulin-producing cell line RINm5F, has been used in short-term experiments to evaluate insulin secretion. We sought to maintain the responsiveness of these cells to stimuli for up to 2 days. We examined the course of new insulin synthesis over this period by measuring at intervals immunoreactive insulin (IRI) in two parts: IRI in the medium (M) and IRI extracted from the cells (C). Control cells were incubated in RPMI 1640/2.8 mM glucose/10% fetal bovine serum/200 micrograms/ml bacitracin (to prevent insulin degradation). The addition of dibutyryl cAMP 10 mM to the experimental dishes significantly increased total (M + C) IRI at 48 hr to 37% above the insulin content of the control dishes (p less than 0.01). Theophylline 10 mM increased total (M + C) IRI by 24% over control (p less than 0.05) after 24 hrs. Glucose, glyceraldehyde, leucine, arginine, glucagon and tolbutamide, other stimulants of insulin production, had no effect. Under the experimental conditions reported here, including the use of bacitracin, IRI synthesis can be studied for up to 48 hr.

Animals↗

Rapid effectiveness of prednisone and thionamides combined therapy in severe amiodarone iodine-induced thyrotoxicosis. Comparison of two groups of patients with apparently normal thyroid glands.

Treatment of amiodarone iodine-induced thyrotoxicosis is often unsuccessful. Nevertheless, severe forms require a rapidly efficient therapy. Twelve patients with severe amiodarone iodine-induced thyrotoxicosis, as demonstrated on clinical and biological findings, were studied. After amiodarone withdrawal, 6 patients (group A) were treated with thionamides alone (carbimazole 60 mg daily and benzylthiouracile 1.5 g daily), and 6 patients (group B) received in addition to the same antithyroid drugs prednisone, 0.50 to 1.25 mg/kg/day for 40 days; in group A, T4 levels did not change over the study period of 40 days; T3 levels decreased only after 30 days; clinical status did not improve. In group B: T3 and T4 levels decreased dramatically at 10 days of treatment, to values significantly lower than in group A; clinical improvement occurred mainly in patients treated with high doses of prednisone; elevated thyroglobulin levels diminished rapidly. Improvement was maintained after cessation of prednisone. The rapid effect of prednisone suggests an impairement of proteolysis of thyroglobulin possibly due to a lysosomal action.

Adult↗

Effects of diabetes type and treatment on zinc status in diabetes mellitus.

Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic patients (IRDM). Plasma zinc concentrations were in the usual range for healthy subjects in these three groups (15.3 +/- 0.9 mumol/L). Urinary zinc excretions were elevated in the IDDM group (18.3 +/- 4.1 mumol/24 h; p less than 0.01 vs normal) and in the NIDDM group (17.5 +/- 3.5 mumol/24 h; p less than 0.01 vs normal), but normal in the IRDM group (11.3 +/- 2.4 mumol/24 h). In 14 NIDDM patients treated with transient continuous sc insulin injections, urinary zinc decreased from 16.5 +/- 2.2 mumol/24 h before insulin treatment to 11.5 +/- 0.3 mumol/24 h after insulin treatment without any modification in plasma zinc concentrations.

Blood Glucose↗

[Physiopathology of non-insulin-dependent diabetes: current data and therapeutic consequences].

Non insulin-dependent diabetes mellitus results from the combination in varying proportions of low plasma insulin levels (insulinopenia), peripheral resistance to insulin and increased hepatic glucose production. Abnormalities of insulin secretion can be demonstrated without and after stimulation. Insulin resistance mainly occurs in skeletal muscle and is primarily due to a "postreceptor" defect. A pancreatic peptide, amylin, may participate in insulin resistance. Hepatic glucose production correlates with high fasting plasma glucose concentrations. Whatever its initial mechanism, hyperglycaemia maintains low insulin secretion and insulin resistance by its toxicity. In the light of these data, the effects of weight loss in obese non insulin-dependent diabetics have become clearer. The action of biguanides on insulin sensitivity is confirmed. Sulphonylureas have a pancreatic and an extrapancreatic action. The normoglycaemia obtained by intermittent insulin therapy can break the vicious circle of glucose toxicity. The use of prolonged insulin therapy is discussed. Finally, new compounds with an original mode of action offer hopes for the future.

Amyloid↗