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Biomedical subjects

J Orgiazzi

Publications and source records attributed to J Orgiazzi.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Iodine consumption in France. National results of the Thyromobile project in a population of schoolchildren aged 6-14 years].

The "Thyromobile" project was initiated to update information on iodine supply in school-children aged 6-14 years in Europe. It involved 4 places in France: Lorraine, Rhône-Alpes, Languedoc-Roussillon, Midi-Pyrénées. Schools of the three former places had been investigated in 1986 during the Mornex's study whereas in the latter they had never been investigated in the past. With a mobile unit, all children (n = 1522) had a thyroid echography performed by the same trained investigator, and urinary iodine concentration was determined in 1458 of them. The mean +/- SD of urinary iodine concentration was 13.0 +/- 7.4 micrograms/dl, but 38% of urinary iodine concentrations were below 10 micrograms/dl and 10% were under 5 micrograms/dl. The prevalence of goitre was 4.1% in boys and 3.1% in girls. There was a negative correlation between urinary iodine concentration and thyroid volume (p < 0.001). Therefore, the results of the "Thyromobile" project show that the places, investigated in France, are not in an area of endemic goitre due to iodine deficiency. However, other epidemiological studies must be done to provide further information about iodine supply in all parts of France.

Adolescent↗
PubMed1995

[Reevaluation of antithyroid drug therapy in Graves disease].

Though antithyroid medical therapy has been used for several decades in the medical treatment of hyperthyroidism, only recently has attention been drawn towards prospective controlled trials concerning the effect in relation to dosage as well as the dosage related to side effects. A review is given in relation to recent investigations on treatment strategies in various parts of the world as well as the most frequently used strategies in Europe. Special attention is given to treatment principles in relation to pregnancy, children and adolescents as well as patients with eye symptoms. Antithyroid drug therapy of hyperthyroidism is a frequent and successful treatment strategy in Europe. Globally, there are still large discrepancies in the treatment strategies, related rather to conventions than to a rational attitude.

Antithyroid Agents↗
PubMed1995

Pancreatic lymph nodes are early targets of T cells during adoptive transfer of diabetes in NOD mice.

The circulation pathway of diabetogenic T lymphocytes prior to insulitis was investigated using adoptive transfer of diabetes in the non-obese diabetic (NOD) mouse model. Transferred T cells were distinguished from recipient T cells using two strains of mice congenic at the Thy1 locus. They were monitored in the pancreas and in several lymphoid organs including thymus, spleen, and lymph nodes from pancreatic, mesenteric, axillary, inguinal and lomboaortic areas, from Day 0 to Day 15 after the adoptive lymphocytic transfer. Immunohistochemical studies showed that at Day 2 post-transfer the pancreatic lymph nodes (PLN) and to a lesser extent the spleen, are the first two organs to be infiltrated. The amount of T cells of donor origin using quantitative flow cytometric analysis was 4% and 2.6% respectively. This percentage increased to 19% in the PLN at Day 15 and did not exceed 7% in the spleen. Analysis of the expression of IL-2 receptor present at the surface of activated T lymphocytes showed that 73% of donor T cells were activated in the PLN within 3 days post-transfer in contrast to 0% in the spleen. The accumulation and activation of T cells in the PLN may imply a role of these lymphoid organs in harbouring the diabetogenic T cells during the early steps of the disease.

Animals↗
PubMed1994

[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↗
PubMed1994

[Thyroid-stimulating hormone receptor and thyroid diseases].

Since the description of the structure of the TSH receptor using molecular biology techniques, it has become possible to analyse the role of anomalies of this receptor in thyroid disorders. Implicated in the pathophysiology of Graves' disease by indirect observations, the autoantigenic role of the TSH receptor has now been clearly confirmed. Nevertheless, the epitopes of the extracellular domain of the receptor corresponding to each type, stimulatory or epitopes of the extracellular domain of the receptor corresponding to each type, stimulatory or blocking, of anti-receptor toward activation or blocking. The events that induce and maintain autoimmunization to the receptor remain hypothetical, but the possible existence of soluble forms of the receptor opens new perspectives. In practice, however, assessment of TSH anti-receptor antibodies is useful in managing Graves' disease and in certain cases of primary myxoedema linked to the presence of blocking antibodies; it is mandatory in pregnant women for detection of foetal disease induced by maternal antibodies. The responsibility of the receptor is sought in other thyroid diseases such as toxic adenoma, rare forms of nonimmunologic, familial hyperthyroidism, simple goiter, nodules and lack of response to TSH. Recently, a mutation mapped into the 3rd intracellular loop has been shown in toxic adenoma. Such discoveries are as important for physicians (and patients) as for cellular biologists.

Autoantibodies↗
PubMed1994

[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↗
PubMed1994

Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism.

The thyrotropin receptor (TSHR), a member of the large family of G protein-coupled receptors, controls both the function and growth of thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non-autoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS-7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated.

Adenoma↗
PubMed1994

[Theoretical aspects of the treatment with antithyroid drugs].

Antithyroid drugs (thionamides such as carbimazole and its active metabolite methimazole, and propyl thiouracile) are taken up by the thyroid gland just as the other anions similar to iodide (perchlorate, thiocyanate, pertechnetate). Their target is the thyroid peroxidase. They block the iodation of tyrosine residues and the coupling of iodotyrosines into iodothyronines. However, beyond the inhibition of thyroid hormone synthesis, antithyroid drugs appear to have the capacity of interfering with the immunological abnormalities involved in Graves' hyperthyroidism: they cure 50% of the patients provided they are maintained for at least 12 months and they significantly decrease the titers of antithyroid antibodies in most of the patients. Potential immunomodulatory effects of antithyroid drugs seem to involve thyroid depletion of iodine which might reduce antigen expression, and scavenging of reactive free radicals generated from oxygen and/or iodide during peroxidation. A direct toxic effect of thionamides on immuno-competent cells seems unlikely. Whatever the mechanisms, more accurate elucidation of the immunomodulatory action of antithyroid drugs might contribute to a better understanding of the thyroid-immune derangements involved in the initiation or perpetuation of Graves' hyperthyroidism.

Adjuvants, Immunologic↗
PubMed1993

[Autoimmune diseases and treatment with interferon-alpha: review of the literature apropos of a case of hyperthyroidism].

We report a case of thyrotoxicosis in a male patient under alpha-interferon (INF-alpha) therapy. Data from the literature show that treatment with IFN-a alone or combined with interleukin-2 (IL-2) can induce dysthyroidism (hypothyroidism, hyperthyroidism, thyroiditis). The frequency of dysthyroidism under INF-alpha therapy ranges from 10 to 40% depending on the authors. During combined INF-alpha and IL-2 therapy these figures reach 20 to 91%. The presence of anthyroid antibodies before treatment makes it more probable that dysthyroidism will occur. The administration of INF-alpha can exacerbate or induce various autoimmune diseases.

Autoimmune Diseases↗
PubMed1993

Reassessment of antithyroid drug therapy of Graves' disease.

Antithyroid drugs have mainly been used to obtain euthyroidism in patients with chronic hyperthyroidism, whatever the cause, and for long-term medical treatment of hyperthyroidism due to Graves' disease. Endocrinologists are faced with the problem of potential side effects and a high relapse rate (30-50%) after an apparently successful treatment. Despite the use of antithyroid drugs for more than four decades, controlled prospective studies have only recently been carried out, comparing high- versus low-dose antithyroid drug treatment of Graves' disease. The present review focuses on differences in treatment regimens in various areas of the world, efficiency, side effects, and the possibility of predicting relapse at the end of antithyroid drug treatment. Several surveys have recently been taken concerning treatment strategy in various parts of the world. Despite the obvious limitations of surveys carried out by a questionnaire, these studies represent the first important efforts to analyze and compare medical strategies for the management of Graves' disease in Europe, the USA, and Japan, between 1986 and 1992. There were clear indications that American thyroidologists appear to be giving up on antithyroid drug therapy more readily and opting instead for generalized ablative treatment with radioactive iodine. In Europe, on the contrary, radioiodine remains largely limited to specific conditions, and antithyroid drugs still remain the major first-line therapy for Graves' disease. In the future, immunomodulation--either alone or in combination with antithyroid drugs--might improve the medical treatment of Graves' disease. Despite the well-known limitations of antithyroid drugs, their use is simple, safe, and advantageous; European endocrinologists thus challenge the American tendency to ablate almost all patients with radioiodine.

Antithyroid Agents↗
PubMed1992

Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals.

The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells.

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.

Adult↗
PubMed1991

[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↗
PubMed1991

Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse.

Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p less than 0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6 +/- 10% vs 2.3 +/- 2%, p less than 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗