Implication of the HLA-DRB3 gene in Graves' disease: predominance of allele Dw24.

Using RFLP, the present study sets off to determine the MHC class II gene polymorphism in Graves' disease, in order to define the HLA-related genetic susceptibility. Considering the preferential link between Graves' disease and the HLA-DR3 antigen, 42 HLA-DR3 Graves' disease patients were studied and compared with 42 HLA-DR-matched controls. Hybridization with a DQ alpha probe of DNAs digested by Taq I revealed a polymorphism of the DR3 haplotype with an overrepresentation of a 2.1 kb(U) fragment in patients, but this was merely a sign of the linkage disequilibrium between U and B8DR3. Hybridization with the DR beta probe of DNAs digested by Taq I yielded more facts. It revealed the overrepresentation of the Dw24 specificity (Taq I:9.8 kb) in DR3 Graves' disease patients. This study thus enabled us to determine precisely the susceptibility linked to the DR3 haplotype, implicating the DRB3 gene and its Dw24 allele, which appear to be the most reliable markers of the disease, providing a higher relative risk than B8DR3.

[Value of the assay of plasma carcinoembryonic antigen and thyrocalcitonin in the detection of medullary cancer of the thyroid with amyloid stroma. Results of a familial survey of 47 subjects]. / Intérêt du dosage de l'antigène carcino-embryonnaire et de la thyrocalcitonine plasmatique dans le dépistage du cancer médullaire de la thyroïde à stroma amyloïde.

During a study of 80 subjects from the same family, 47 persons underwent clinical examination and blood sampling for carcinoembryonic antigen and thyrocalcitonin. A preliminary investigation had shown that two members of the family had histologically confirmed amyloid stroma MTC, 2 others had probable malignant disease, 3 children died of intestinal obstruction in the neonatal period, and a fourth child operated for megacolon when 3 days old was the descendant of 2 subjects with probable thyroid carcinoma. Three years later, the study was updated and concentrated on the patients with the highest risk of developing malignant disease. The diagnosis was confirmed in one patient considered to have probable MTC. One case of malignant disease was discovered in a child considered to be normal 6 years previously. Three other patients, considered to be normal 6 years before had very probable MTC. These results indicated that familial investigations including plasma calcitonin measurements after pentagastrin stimulation, are valuable when amyloid stroma MTC is diagnosed in one member of the family. This test should be repeated periodically. The surgical indications in patients with abnormal responses should take into consideration the psychological context.

[Graves' disease. Predominance of the DRw3 antigen (author's transl)]. / Maladie de Basedow. Prédominance de l'antigène DRw3.

HLA-A, B, C antigens were studied in 86 white european patients with Graves' disease, using a lymphocyte toxicity microtechnique and the results were compared with those obtained in 356 healthy subjects. HLA-D (DR) antigens were studied by the same technique after prolonged incubation and the results were compared with those of 100 healthy controls. The incidence of DRw3 was 51.16% in the patients as against 20% in controls, the difference being highly significant (pc--PC less than 0.0003) - corrected p = p multiplied by the number of antigens tested. There was also a significant (pc less than 0.001) increase in HLA-BB: 44.19% against 22.47%, and in HLA-A1: 40.7% against 28.93% (pc less than 0.03). Conversely, there was a decrease in the incidence of HLA-B12: 12.79% against 31.74% (pc less than 0.01). B8 was found to be associated with DRw3 in 37 of the 86 patients, but in only 13 of the 100 controls (p less than 0.00003). There was no correlation between the HLA antigens and the clinical features of the disease (presence or absence of goitre and exophthalmos, severity of clinical or biological symptoms). These results are in agreement with those of other studies reporting an increase in HLA-B8. The increase in HLA-A1 is probably due to an accentuation of the unbalanced linkage with B8. The major finding was the predominance of the DRw3 antigen, also found by other authors working with a mixed lymphocyte culture. It seems therefore possible that the putative Graves' disease susceptibility antigen is present on the sixth chromosome, near to HLA-D (DR).

Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity.

OBJECTIVE: To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet. DESIGN: A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study. SUBJECTS: In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMI >or=28 kg/m(2)) were randomized to treatment with orlistat (n=346) or placebo (n=350). MEASUREMENTS: Body weight, anthropometry, lipid and glycemic control parameters and blood pressure. RESULTS: After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lost >or=10% of their initial weight (P=0.04). A significantly greater number of patients receiving orlistat treatment maintained this >or=10% weight loss compared to those receiving placebo (28.1 vs 13.8%; P<0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18 mmol/l; P<0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%; P<0.001). CONCLUSION: A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.