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H Allannic

Publications and source records attributed to H Allannic.

At least 37 records · Page 2Linked to original sources

Combined analysis of islet cell antibodies which cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in subjects at risk for IDDM.

With regard to progression to diabetes, ICA cross-reactive with mouse pancreas, antibodies to the M(r) 64,000 islet antigen (64K), antibodies immunotrapping brain GAD activity, and IAA were analysed in 53 ICA-positive first-degree relatives of IDDM patients and 18 ICA-positive schoolchildren without a family history of diabetes. Sera from 29 (55%) relatives did not bind to mouse pancreas, whereas 24 (45%) displayed cross-species reaction. ICA titres on human and mouse pancreas were weakly correlated in the overall population (p < 0.05) but more strongly (p < 0.01) in only those subjects who displayed antibodies on tissues from both species. GAD and 64K antibodies were detected in 31% and 35% of relatives. In schoolchildren, the frequencies of cross-species reactive ICA (22%), GAD antibodies (6%), 64K antibodies (22%), and IAA (6%), were lower (p < 0.05) than in relatives. A strong correlation (p < 0.0001) was observed between GAD and 64K antibodies. GAD or 64K antibodies were strongly correlated with ICA on human pancreas (p < 0.0001) but poorly with ICA on mouse pancreas (p = 0.05). After pre-incubation of sera with brain homogenate, ICA titres were unaffected on mouse pancreas but reduced on human pancreas. ICA-positive subjects who displayed neither cross-species reactive ICA nor GAD or 64K antibodies were more frequent (p < 0.05) among schoolchildren than relatives, whereas subjects who displayed all antibody specificities were more numerous (p < 0.04) in relatives. All relatives with ICA binding only to human pancreas, as well as all schoolchildren, permanently displayed an AIRG higher than the first control percentile and remained non-diabetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Combined analysis of islet cell antibodies that cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in type I diabetic patients.

OBJECTIVE: A combined analysis of whether islet cell autoantibodies (ICAs) are cross-reactive with mouse pancreas, with glutamate decarboxylase (GAD) antibodies, and with 64K antibodies was performed in a large sample of recently diagnosed type I diabetic patients. The disappearance rates of these different autoantibodies were compared in some patients after onset of the disease. The aims were to determine patterns in GAD/64K antibodies with regard to cross-species reaction of ICA and to assess whether GAD could contribute to ICA positivity in mouse and human pancreases and whether the simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma. RESEARCH DESIGN AND METHODS: ICA detected by immunofluorescence in human and mouse pancreases, antibodies immunoprecipitating the 64K rat islet antigen, and antibodies immunotrapping brain GAD activity were quantified at diagnosis of diabetes in 95 patients and in sequential samples during 1 year after diagnosis in 13 patients. The contribution of GAD to ICA positivity in mouse and human pancreases was evaluated by the analysis of correlations between tests and by the ability of brain homogenate to block ICA reactivity in pancreases from both species. RESULTS: ICAs were detected in human pancreases in sera from 63 (66%) patients, among which 61% bound also to a mouse pancreas. GAD and 64K antibodies were strongly correlated (P < 0.0001) and were detected in 69 and 73% of the patients, respectively. All but two patients with ICA in human pancreas also displayed either ICA in mouse pancreas or GAD/64K antibodies. Among 32 patients without ICA in human pancreas, 54% displayed either GAD/64K antibodies or ICA in mouse pancreas. Only 16% of the patients displayed neither ICA nor GAD/64K antibodies. A correlation (P < 0.005) was found between ICA in human and mouse pancreases. GAD or 64K antibodies were strongly correlated with ICA in human pancreas (P < 0.0001), but not with ICA in mouse pancreas. After preincubation of six sera with GAD-containing brain homogenate, ICA titers were unaffected in mouse pancreas but reduced in human pancreas. ICA titers in mouse pancreas were decreased after 3 months (P < 0.01) in diabetic patients, contrasting with the stability of ICA in human pancreas and GAD antibodies by 1 year after diagnosis. CONCLUSIONS: According to cross-species reaction, we confirm the heterogeneity of ICA in a large series of type I diabetic patients, ICAs that cross-reacted with mouse pancreas being more frequent than ICAs without cross-species reactivity. GAD and 64K antibodies were also present in a majority of patients. The simultaneous search for all the antibody specificities enhances the detection of autoimmune stigma so that only a few patients did not display any autoantibody at diagnosis. GAD is not the target of ICAs in mouse pancreas, whereas GAD accounts for ICA positivity in human pancreas. The conclusion that ICAs in mouse pancreas are not GAD-reactive is reinforced by the fact that they are more transient after onset of diabetes than are GAD antibodies or the complex mixture of ICAs in human pancreas.

Adolescent↗

[Treatment of Basedow disease with synthetic antithyroid drugs. Evaluation of the effect of the duration of medical treatment on its long term efficacy].

The modalities of Graves' disease by antithyroid drugs are controversial. In particular, the duration of treatment is of great interest. Physicians managing Graves' disease patients have used variable periods of treatment. Some have proposed a few month short time therapy while others recommend an average of two years; others physicians did not used fixed periods but propose various criteria for the follow up (TSH us, early iodine uptake, TSAb, TBIAB); the treatment being stopped when these markers normalized. The present analysis clearly suggests that long term treatment (eighteen months) improves the prognosis of the disease and that longer therapeutic periods are not necessary. For the future we have to identify the best remittance markers, the aim being to propose drug withdrawal according to the individual evolution of these markers.

Antithyroid Agents↗

[Susceptibility of LDL to lipid peroxidation in non-insulin-dependent diabetes mellitus with or without macroangiopathy].

Since oxidized LDL may play a role in the genesis of atheroma, which is the primary complication of non-insulin-dependent diabetes mellitus (NIDDM), we investigated whether the LDL of diabetic patients were more prone to oxidation than those of healthy controls. We therefore studied the susceptibility of LDL to oxidation by phenylhydrazine (LDL-PO) in NIDDM patients with or without macroangiopathy, and in controls. Results showed that the LDL of patients with macroangiopathy (n = 50) were more susceptible to oxidation than those of both NIDDM patients without vascular complications (n = 50) and controls (n = 50). In diabetic patients, there was a positive correlation between LDL-PO and the following parameters: total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B. In contrast, there was no correlation between LDL-PO and the parameters of glycemic control (fasting glucose, HbAlc). After analyzing the composition of LDL, it appeared that LDL-PO values in diabetic patients were positively correlated with those of all LDL constituents. The increase in LDL-PO observed in the group of NIDDM patients with macroangiopathy could be a consequence of an increase in the LDL triglyceride content in these patients.

Apolipoproteins B↗

Plasma malondialdehyde in type 1 and type 2 diabetic patients.

Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substances (TBARS) in 117 diabetic patients and 53 controls. Patients were divided into groups and subgroups according to the type of diabetes (type 1 and type 2) and the existence or not of vascular complication (macro- or micro-angiopathy). Results showed that TBARS concentrations were significantly higher in type 1 (P < 0.0001) and type 2 (P < 0.001) diabetic patients than in the control group. The plasma TBARS concentrations in type 1 and type 2 diabetic patients did not differ significantly. Among the patients with vascular disease, type 2 diabetic patients with macroangiopathy had significantly higher TBARS concentrations than patients with no vascular complication (P < 0.05). Whichever the type of diabetes, there was no correlation between TBARS concentrations and glycaemic control: glycosylated haemoglobin, fasting blood glucose. This study confirmed the existence of lipid peroxidation disorders in diabetic patients.

Adult↗

[Detection of subjects at risk of type 1 diabetes. GOFEDI. Groupe Ouest-France pour l'Etude du Diabète Insulino-dépendant].

The so-called type 1 (insulin-dependent) diabetes is an autoimmune disease occurring in genetically predisposed subjects. The clinical onset of the disease is preceded by a subclinical period during which insulin-producing cells are progressively destroyed by immunological effectors. This prediabetic phase can be detected by the presence of autoantibodies directed against islet cells and sometimes associated with anti-insulin antibodies in children, and later on by the disappearance of the early insulin secretion peak in response to intravenous glucose. It is at this prediabetic phase that immunomodulators specific to the antipancreas process and devoid of side-effects will be used, when available, and that an early insulin therapy will be instituted.

Biomarkers↗

[Is thyroid hormone useful in the prevention of nodular recurrence after hemithyroidectomy?].

The frequency of recurrence of thyroid nodule following hemithyroidectomy is variably assessed according to the individual authors. Few studies put a figure to ultrasonographic recurrence, clinical recurrence only being taken into account: its percentage ranges from 10 to 20%, increasing with the time lapse after thyroidectomy. Attempts to prevent recurrence are based on an approach of the physiopathology of thyroid nodules. Clinical and epidemiological studies of patients with goiters suggest that TSH may play a role in the generation of goiters, as has been confirmed by experimental work. However, several other local autocrine or paracrine growth factors may also be involved in the generation of goiters, including IGF I and IGF II (Insulin Growth Factors), FGF (Fibroblast Growth Factor), EGF (Epidermal Growth Factor), TGFB (Transforming Growth Factor beta). On the basis of the possible role of TSH in goiter generation, some teams have advocated a postoperative course of thyroid hormones aimed at limiting thyreostimulin production. These studies, most of them retrospective studies, do not allow drawing a meaningful conclusion because their methods are open to criticism and the results observed are disparate. On a whole, although thyroid hormone therapy is often used after hemithyroidectomy, the physiopathological bases of its prescription are disputable, and the results obtained in terms of recurrence of nodules are not conclusive enough. It is therefore desirable to set up randomized studies.

Humans↗

[Severe oligospermia with normal FSH. Comparison between radioimmunologically and immunoradiometrically determined levels of LH].

We have noted in a group of oligospermic patients with normal FSH levels and normal sized testes that there can be a significant drop in the LH levels estimated by IRMA, compared with a control group of fertile men. On the other hand, there is no correlation between IRMA and RIA levels of LH in oligospermic men when there is such a correlation in the control group. As oligospermia is usually testicular in origin preliminary results suggest that there may be a disturbance of gonadotrophin secretion in one type of oligospermia and we intend to continue this preliminary study.

Adult↗

[Screening and prevention of type 1 diabetes].

Insulin-dependent diabetes mellitus is preceded by a prodromal phase during which insulin-secreting cells are progressively destroyed by immunological factors. Among genetically predisposed and high risk subjects, this phase of prediabetes can be identified by detection of immunological and metabolic markers. For these prediabetic subjects, specific immunomodulators, without adverse effect, will be available.

Biomarkers↗

No major monoclonal lymphocyte population in the thyroid of patients with Graves' disease: study of gene rearrangement by restriction fragment length polymorphism and polymerase chain reaction.

The present study aimed at determining the mono-, oligo-, or polyclonal nature of intrathyroid lymphocytes at the DNA level in patients with Graves' disease. Two techniques were used to seek monoclonal rearrangement in DNA derived from intrathyroidal lymphocytes obtained from six patients. The first was restriction fragment length polymorphism using two specific probes from the B-chain of T-cell receptor and the other from the heavy chain immunoglobulin gene; the second was polymerase chain reaction using a couple of specific primers from the variable and joining regions of heavy chain immunoglobulins. The results for the patients with Graves' disease were compared with those obtained for circulating T-and B-lymphocytes, granulocytes (negative controls), and T- and B-leukemic cells (positive controls). The results with restriction fragment length polymorphism favored a polyclonal origin for the lymphocytes in all cases, since no rearrangement was visualized. The results with polymerase chain reaction were analogous, and the technique was 10 times more sensitive in the detection of rearrangement.

Adult↗

[Pregnancy in the diabetic woman. Incidence of malformations, of macrosomia, update on obstetrical management].

Perinatal mortality for infants born to diabetic mothers has dropped in the years from the 1950's when it was 20% to less than 3% by the end of the 1980's. In spite of this considerable reduction which is due to careful observation and multidisciplinary management in this type of pregnancy, the congenital malformation rate is 4 times greater than with the general population (3%) and the rate of spontaneous abortions is double (13%). The caesarean section rate is 5 times higher (18%). In bringing out a retrospective study we have attempted to analyse the endocrinological and obstetrical features of the cases.

Cesarean Section↗

[Synthetic antithyroid drugs and Basedow's disease or the choice of a therapeutic strategy].

We present the conclusions of two prospective studies of patients examined at their first manifestation of Graves' disease and treated with antithyroid drugs (ATD). The purpose of the first study was to investigate the effects of long-term treatment: the patients were given carbimazole in degressive doses without hormone replacement for 18 months, the followed up for 2 to 6 years after drug withdrawal. The second study was designed to determine the effect of treatment duration on the prognosis: the patients were given an ATD according to the same protocol for a duration randomly set at either 6 or 18 months, then seen again 2 years after ATD withdrawal. The results showed that after 18 months of treatment at least 50 percent of the patients could be expected to remain in remission for 6 years. Remissions were less frequent when treatment was shorter (41.7 percent after the 6 month treatment versus 61.8 percent after the 18 month treatment, with a 2 years' follow-up; P less than 0.05). The relapses that occurred came early: 70 percent of them took place within the first post-treatment month. This article also provides evidence of high T3 and/or T4 levels without signs of thyrotoxicosis during the post-treatment clinical course; these exclusively biochemical relapses spontaneously disappeared and may have been expressing epidoses of active thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acute insulin response to intravenous glucose, glucagon and arginine in some subjects at risk for type 1 (insulin-dependent) diabetes mellitus.

The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a "normal" (n = 11; Group IIa) or a "low" insulin response to i.v. glucose (n = 10; Group IIb). Groups I and IIa displayed similar insulin responses to the three secretagogues. In contrast, Group IIb demonstrated lower insulin responses to both glucagon and arginine than control subjects (p less than 0.007 and p less than 0.04 respectively) or than "normo-responders" to glucose (p less than 0.007 and p less than 0.04 respectively). In Group IIb however, arginine-stimulated insulin release was increased compared to the response to glucose (p less than 0.006), while glucagon and glucose led to non-statistically different responses. Five "low-responders" developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p less than 0.05 and p less than 0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the "low-responders" who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p less than 0.006) or did not (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of thyroperoxidase and microsomal antibody assays in sera from patients with Graves disease.

Anti-microsomal (anti-Mic Ab) and anti-thyroperoxidase antibody activities (anti-TPO Ab) were compared by using commercially available radioassay kits. Sera were collected from 52 patients with Graves disease before and after administration of carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). The two antibody concentrations were significantly correlated, both before treatment (r = 0.835, P less than 0.001, n = 52) and at the end of treatment (r = 0.584, P less than 0.001, n = 52). Twenty-nine (Group I) of the 52 patients were in remission for two years after drug withdrawal, whereas 23 (Group II) relapsed. Within each group, the anti-Mic and anti-TPO Ab concentrations were significantly correlated (Group I: r = 0.781, P less than 0.0001; Group II: r = 0.866, P less than 0.0001). Relapse vs nonrelapse was linked to the antibody positivities measured before treatment: 91% vs 65% (chi 2 = 4.75, P less than 0.02) for anti-Mic Ab and 87% vs 62% (chi 2 = 4.05, P less than 0.02) for anti-TPO Ab. We conclude that assays of anti-Mic and anti-TPO Ab are equally reliable analytically and equally informative clinically. Because of its rapid implementation, the anti-TPO assay may advantageously replace anti-Mic Ab assay, especially for forming a prognosis of Graves disease.

Autoantibodies↗

Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration.

A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗