PubMed Health⌕ Search

Biomedical subjects

R Sapin

Publications and source records attributed to R Sapin.

At least 19 recordsLinked to original sources
PubMed2003

[Sub-clinical hypothyroidism, towards the end of a controversy?].

DEFINING THE PROBLEM: Sub-clinical hypothyroidism, defined as a moderate and isolated increase in TSH levels, is a common syndrome and is the first phase of a progressive disease. However its treatment remains controversial. Some anamnestic, clinical and biological (anti-thyroperoxidase antibodies) parameters contribute in identifying the patients most likely to progress towards overt hypothyroidism. WHAT CAN BE EXPECTED OF TREATMENT? Several clinical studies have described cardiovascular, neuromuscular and lipid disorders in these patients, but administration of levothyroxine has provided varying results and does not enable the distinction between a pharmacological-like intrinsic effect of the thyroid hormone and the true benefits imputable to the correction of TSH, in the absence of any large interventional study. More studies are required to better identify the patients who will benefit most from hormone replacement.

Humans↗
PubMed2001

The HLA-DQB alleles and amino acid variants of the vitamin D-binding protein in diabetic patients in Alsace.

BACKGROUND: The HLA-DQB1 chain, in particular the amino acid in position 57, and genetic variants of the vitamin D-binding protein (DBP) have been reported to be associated with type 1 diabetes. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: codons 416 GAT --> GAG (Asp --> Glu) and 420 ACG --> AAG (Thr --> Lys). We compared distribution of DQB1 alleles and amino acid variants of DBP in type 1 diabetic patients (n = 44) in the Alsacian population and in healthy controls (n = 58). METHODS: The second exon of the DQB1 gene and exon 11 of DBP were analyzed by restriction mapping after polymerase chain reaction. RESULTS: A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) was observed in diabetic subjects as compared to controls (94.3 vs. 32.8%; p < 0.001). Combinations other than Ala/Ala carried the highest relative risk (OR = 52; p < 0.001). The analysis of the polymorphism in exon 11 of DBP showed a significant difference in the allele frequency of the HaeIII site, but not of the StyI site between patients and controls. Allele frequencies of HaeIII in diabetic subjects were 36% and 64% for Asp and Glu respectively (p < 0.001; chi(2) = 29.5). The frequency of Asp/Asp and Glu/Glu genotypes was increased in controls and diabetic subjects respectively. DBP alleles in individuals carrying the DQB1 NA combination revealed that 46.6% of diabetics were DBP Asp/Glu, but this was not statistically significant using the Fisher exact test (16/31 vs. 0/3; p = 0.23). CONCLUSIONS: The study of the DQB1 chain confirmed the value of alleles encoding for an amino acid different from Asp in position 57 (NA) in the susceptibility to type 1 diabetes. The allele frequency of the HaeIII site, but not of the StyI site, differed between patients and controls (HaeIII p < 0.001; StyI p > 0.05).

Adolescent↗
PubMed2001

Serum thyroxine binding capacity-dependent bias in five free thyroxine immunoassays: assessment with serum dilution experiments and impact on diagnostic performance.

OBJECTIVES: To assess the presence and magnitude of a serum thyroxine binding capacity (sBC)-dependent bias in five free thyroxine (FT(4)) immunoassays, compared with equilibrium dialysis (ED). The exhibited bias is confronted with clinical results from previous studies to evaluate its impact on FT(4) determination in sera with various sBC. DESIGN AND METHODS: The sera of three pregnant women and three non thyroidal ill (NTI) patients were serially diluted in an inert buffer to progressively decrease the sBC. FT(4) values were measured in diluted and undiluted samples with the six assays. RESULTS: As a function of increasing dilution performed on pregnancy sera, except for ED and Vitros ECi FT(4,) the other four FT(4) assay results decreased to different degrees, in the following order: two-step GammaCoat RIA< Elecsys< ADVIA:Centaur< Amerlex-MAB RIA. In sera from NTI patients, the decrease was more marked and found at high dilution with the Vitros ECi assay. Data from previous studies showed that FT(4) measured with biased assays were decreased only in samples from very severely NTI patients with low sBC and that FT(4) results in pregnancy sera with high sBC were not significantly biased. CONCLUSIONS: The dilution test is a sensitive alarm to assess sBC-dependent bias in FT(4) assays. For all FT4 assays and particularly when a bias is observed, documentation should be sought on the diagnostic performance of the assay and supported by a detailed clinical study including samples with low sBC. Physicians should still be educated about the limitations of FT(4) assays.

Blood Proteins↗
PubMed2001

High antigenicity of intraperitoneal insulin infusion via implantable devices: preliminary rat studies.

Intraperitoneal insulin infusion of Genapol stabilized insulin via implantable devices significantly improves diabetes control and hypoglycemia frequency in type 1 diabetes while it increases insulin antibody levels. Causes for this particular antigenicity remain unknown. The role of insulin modifications occurring in the reservoir on the antigenicity observed was assessed by comparing the antigenicities of the insulin coming from the vial or from the pump reservoir. Rats were injected intraperitoneally with insulin sampled either from a vial (group 1) or from a pump reservoir during a refill of a clinical trial (group 2). Two control groups, one without insulin, the second one receiving a mixture of silicone and insulin were also studied. Human insulin antibody levels were assessed by RIA 10 days after 4 weekly immunizations. AIA levels were higher in group 1 compared to group 2 (P = 0.003 for the first experiment, P = 0.04 in the second experiment). The increased antigenicity of the insulin sampled from the implanted pump might be due to the insulin modifications occurring during the storage in the device. Insulin aggregates could be involved in this antigenicity since they are known to be antigenic and their concentration was shown to be related to the amplitude of the antigenic response.

Animals↗
PubMed2000

Concordance of eight kits for antithyroid peroxidase autoantibodies determination.

Numerous methods are proposed to quantify antithyroid peroxidase autoantibodies. No standardization exists but most assays use the standard MRC 66/387 with a calibration factor. Costs of the tests vary between the different kits. We evaluated the concordance of eight peroxidase autoantibodies assay kits in two centres, using a panel of sera from 269 subjects: controls (n=100), patients with autoimmune thyroid disease (n=77; Graves' disease, Hashimoto's thyroiditis), patients with non-autoimmune thyroid disease (n=69; nodular goiter, differentiated thyroid carcinoma) and individual sera with thyroglobulin antibodies only (n=23). The concordance between the eight methods was high, ranging from 88.3% to 98.8% with the total panel of sera. The majority of assays demonstrated high diagnostic performance. We encountered some false-positive results at borderline positive levels, and the nonrecognition of some sera by competitive assays.

Autoantibodies↗
PubMed2000

Contribution of total and intact proinsulins to hyperinsulinism in subjects with obesity, impaired glucose tolerance or type 2 diabetes.

The recent development of specific radioimmunoassays of insulin (Ins) and proinsulin (PI) led some authors to question the classical data on insulinosecretion in patients with abnormal glucose tolerance. The aim of this work was to determine the participation of intact proinsulin (iPI) and its split fragments to total insulinsecretion in obese subjects and in various stages of glucose intolerance determined by an oral glucose load according to the WHO recommendations. Five groups were constituted: non obese controls (C), obese subjects with normal glucose tolerance (O), non obese subjects with impaired glucose tolerance (I), obese subjects with impaired glucose tolerance (OI) and diabetic patients (D). The basal level of total Proinsulin (tPI) of D and OI was significantly higher than that of C, but the tPI/Ins ratio did not differ between the five groups. After glucose load, this ratio tended to be higher in D, but not significantly. No statistical difference between groups was observed for the iPI/Ins ratio. These results indicate that the determination of tPI is at least as informative or more than that of iPI. Furthermore, the proportionally constant participation of PI to insulin secretion observed in various stages of glucose intolerance suggests that the results obtained in the past with non specific insulin radioimmunoassays remain valid.

Adolescent↗
PubMed1999

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗
PubMed1998

Evaluation of Elecsys free triiodothyronine assay: relevance of age-related reference ranges.

OBJECTIVE: This study aimed at evaluating Elecsys free triiodothyronine (FT3) assay performed on an Elecsys 2010 system, while paying special attention to age relationship in euthyroid subjects. DESIGN AND METHODS: FT3 levels were measured in 149 euthyroid control subjects aged between 2 and 92 years old, 33 hyperthyroid and particular euthyroid patients: female in the last 3 months of pregnancy (n = 30), nonthyroidal ill hospitalized in medical (NTlm, n = 31), or intensive care units (NTlc, n = 31) and amiodarone-treated (n = 27). RESULTS: FT3 was inversely related to age in controls (r = -0.67). Three reference ranges were used: below 20 years 4.5-9.0 pmol/L, between 20 and 60 years 3.9-7.2, and over 60 years 2.4-6.5. Compared to age-matched controls, FT3 decreased in pregnancy, NTlm, NTlc, and amiodarone groups. Use of age-related reference ranges improved the specificity markedly in amiodarone patients and to a lesser extent in NTlm and TClc patients. CONCLUSIONS: The reliability of the Elecsys FT3 assay was found to be satisfactory for clinical use, when the age of patients was taken into account.

Adolescent↗
PubMed1998

[Euthyroid sick syndrome: recent physiopathologic findings].

INTRODUCTION: Patients with nonthyroidal disease frequently exhibit abnormal thyroid function tests; this is referred to as euthyroid sick syndrome. The clinical significance of this syndrome is unknown: abnormal endocrine reaction with reduced triiodothyronine (T3) at the tissue level, or adaptation to stress protecting the body against exaggerated catabolism. CURRENT KNOWLEDGE AND KEY POINTS: Recent advances in the underlying mechanisms concern the role of deiodinase and of the transport of thyroid hormone in tissues. Various factors acting on deiodinase or on transport system, such as medications and nutritional factors, have been implicated. Considerable interest has raised concerning the role of cytokines. Some cytokines may act at every level of the thyrotropic axis, but their real action in vivo remains unclear. Nutritional factors have a great impact on thyroid hormone metabolism, but the mechanism of the decrease in T3 induced by starvation is not identified. The role of the decrease in type I hepatic deiodinase has been recently challenged. FUTURE PROSPECTS AND PROJECTS: Despite its complexity, euthyroid sick syndrome is a model for the study of thyroid hormone metabolism regulation. Characterisation of the thyroid hormone transport proteins will lead to significant advances in the understanding of the syndrome.

Animals↗
PubMed1998

Improved specificity of a new direct assay for urinary cortisol: application in corticoid treated patients.

Twenty four hours urinary free cortisol (UFC) excretion has been determined in 35 eucortisolic control patients, in seven of them before and after tetracosactide (Synacthen) stimulation and in 18 patients treated by anti-inflammatory steroids. Results of the new direct Immunotech RIA (DIm) were compared to those of the INCSTAR RIA kit with (ECA) or without methylene chloride extraction (DCA). In controls DIm UFC (106.2+/-45.8 nmol/24h) was significantly lower than DCA UFC (397+/-119 nmol/24h) and than ECA UFC (127+/-49 nmol/24h). After tetracosactide stimulation, median of DCA/DIm ratio decreased from 3.61 to 1.88 whereas ECA/DIm ratio did not change significantly (1.31 to 1.06). In treated patients most DCA and ECA results were over the upper limit of controls but only 5 DIm results were increased. DIm assay showed good specificity and practicability and may be used with benefit in the evaluation of the adrenal gland function.

Anti-Inflammatory Agents↗
PubMed1997

Anti-insulin antibodies in insulin immunometric assays: a still possible pitfall.

Insulin was assayed directly using radioimmunoassay and immunometric assay in 31 sera containing anti-insulin antibodies. Anti-insulin antibodies were determined by radio-binding-assay. Insulin measurements were compared with those of free (unbound to antibodies, polyethylene glycol precipitated) insulin measurements. Compared with free insulin concentrations, radioimmunoassay and immunometric assay yielded falsely increased insulin results. The degree of overestimation by radioimmunoassay and by immunometric assay correlated with the anti-insulin antibody value. Anti-insulin antibodies still remain a possible pitfall in the insulin-specific immunometric assays which are now being widely used.

False Positive Reactions↗