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To investigate the potential of back propagation (BP) neural networks (NNs) in the discrimination of benign from malignant thyroid lesions.The study was performed on May-Grünwald-Giemsa-stained smears obtained by fine needle aspiration (FNA). Using a custom image analysis system, 26 features that describe the size, shape and texture of the nucleus were measured from each cell. The cases were distributed according to categories, as follows: 25 cases of goiter and follicular adenomas, 1 case of follicular carcinoma, 12 cases of papillary carcinoma, 6 cases of oncocytic adenoma, 3 cases of oncocytic carcinoma and 4 cases of Hashimoto thyroiditis. From each case about 100 nuclei were measured; they formed a pool of 13,850 feature vectors. Out of this pool, 2,770 vectors were randomly selected to form the training set, and the remaining 11,080 vectors formed the test set.The application of a BP NN on the nuclear measurements permitted correct classification of 90.61% nuclei. Classification at the patient level was performed using a hypothesis test for proportion and two different hypothesis values, one equal to the overall accuracy of the NN and one equal to 50%. The second method permitted correct classification of 98% of patients.These results indicate that the use of NNs combined with image morphometry and statistical techniques may offer useful information on the potential malignancy of thyroid cells and may improve the diagnostic accuracy of FNA of the thyroid gland, especially in cases classified as suspicious for malignancy.

Diabetic patients (3% of the French population) have a higher risk of coronary and peripheral vascular disease than non-diabetic subjects and develop long-term microvascular renal and retinal complications. Abnormalities of coagulation, haemostasis and fibrinolysis have been demonstrated in diabetics and contribute to these complications. The prescription of antithrombotics is therefore common in these patients. Platelet antiaggregants (aspirin and ticlopidine) are effective in primary and secondary prevention in reducing the overall number of vascular events (reduction of 17% in the last ATC meta-analysis) and of coronary and cerebrovascular complications in particular. Two studies have shown a preventive effect of antiaggregants on diabetic retinopathy in its initial stages. With regards to the value of the use of these agents, there are few complications which may be limited by appropriate measures. One problem lies in the choice of aspirin dosage, most studies having been performed with high doses ranging from 500 to 1,300 mg per 24 hours. It is therefore difficult to recommend doses less than 300 to 500 mg per 24 hours. The prescription of anticoagulants (heparin, vitamin-K antagonists) is not associated with more problems in diabetics than in non-diabetics. The same applies to the use of thrombolytics in the acute phase of myocardial infarction: the risk of haemorrhages, especially intraocular, is only theoretical, only one case (regressive) having been reported to date. In conclusion, diabetes is more a priviledged indication than a contra-indication to the use of antithrombotic, platelet inhibitor, anticoagulant and thrombolytic agents.

The following study has been undertaken to establish if antiradicalar agents (1) and serum selenium are linked to hypertension and micro and macrovascular complications in diabetic patients. We also addressed the question of any nutritional role of selenium in diabetes, by searching for any relation between selenium and BMI (Body Mass Index) in patients with type 1 insulin dependent (IDDM) and type 2 non insulin dependent (NIDDM).

Objectif Evaluer l’incidence de la retinopathie diabetique a 3 ans grâce au reseau de telemedecine Ophdiat, et les facteurs de risques cliniques et biologiques associes. Materiels et methodes Il s’agit d’un etude retrospective portant sur 254 patients ayant beneficie de 2 depistages de la retinopathie diabetique a 3 ans d’intervalle grâce aux retinophotographies effectuees sur le reseau de telemedecine Ophdiat. Ce depistage a ete realise lors d’un bilan annuel clinique et biologique complet en diabetologie. Resultats L’incidence a 3 ans est de 14 % (IC 9,6–18,4 %). La duree du diabete et la presence d’une microalbuminurie sont les 2 facteurs significativement associes a l’incidence de la retinopathie (p Discussion Il s’agit des premieres donnees francaise d’incidence de la retinopathie diabetique. Comparee aux autres etudes epidemiologiques, l’incidence retrouvee est peu elevee compte tenu de la duree du diabete, mais il s’agit d’une population hospitaliere au suivi regulier presentant un diabete bien equilibre. Lors du depistage de la retinopathie diabetique, la presence d’une microalbuminurie est une donnee sous evaluee en pratique ophtalmologique.

In addition to their initially recognized antiviral activity, interferons are known to have a number of effects on the immune system. The role of alpha-interferon (alpha-IFN) has been evaluated in 8 studies, including 573 patients, aimed at determining the prevalence, clinical course and predictive factors of autoimmune dysthyroidism in patients treated with alpha-IFN. Two major categories of patients were treated with alpha-IFN: those with cancer and those with chronic viral hepatitis. Two types of interferon were used: human leukocyte IFN and recombinant IFN. Among the 542 patients in which thyroid function was evaluated, 47 (8.7%) had clinical or biological dysthyroidism: hypothyroidism in 25 (53%), hyperthyroidism in 13 (28%) and biphasic hyper-hypothyroidism in 9 (19%). The delay to onset was known in 44 patients (mean 9 months, range 1.5 to 23 months). Dysthyroidism was temporary in certain patients and did not require treatment, but antithyroid drugs were required in others. The prevalence of antithyroglobulin and/or antimicrosomal antibodies varied from 0 to 20% (mean 13.7%). The prevalence of antithyroid stimulating hormone receptor antibodies appeared to be lower than that of antithyroid antibodies. The pathogenic mechanism of dysthyroidism in patients given alpha-IFN remains unknown, but could result from the induction of antithyroid antibodies or an increase in pre-existing levels. Abherent expression of HLA-DR antigens on the surface of the thyrocytes has been proposed as a possible factor, although gamma-IFN and not alpha-IFN leads to the expression of class II antigens. It has also been shown that alpha-IFN induces the expression of class I antigens on thyrocytes, indicating that the observed dysthyroidism might result from an over-expression of class I antigens which would facilitate direct activation of cytotoxic T cells. In summary, alpha-IFN can induce dysthyroidism in about 1 out of 10 patients, probably by the induction or stimulation of autoimmune phenomena. The positive predictive value of antithyroid antibodies is modest, about 60%, but the negative predictive value is high at 93%. Thyroid function should be monitored closely in patients given alpha-interferon.

Beta-cell dysfunction is prominent in Type 2 (non-insulin-dependent) diabetes mellitus. Four types of abnormalities have been described. Oscillatory pattern of insulin-secretion is impaired, with a loss of high frequency pulses and with a reduction in amplitude of slow oscillations. This impairment takes place early in the course of the disease, as does the loss of the first phase of insulin secretion after intravenous glucose. Quantitative (insulin deficiency in relative and absolute terms) and qualitative abnormalities (excess in proinsulin and in 32-33 split proinsulin) have been also observed in Type 2 diabetes. One or several genetic defects seem to be responsible for the development of this beta-cell dysfunction and for Type 2 diabetes mellitus.

The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.

In patients with insulin-dependent (Type 1) diabetes mellitus abnormal endothelial cell proliferation was considered as one of the possible explanations for the occurrence of retinopathy. Since monocyte-derived factors have been proposed to be involved in endothelial cell growth regulations we have measured the effect of monocyte-conditioned medium (MO-CM) on endothelial cell proliferation and the production of Tumor necrosis factor alpha and interleukin 1-beta, cytokines known to alter endothelial cell functions. The effect of MO-CM in 20 patients with Type 1 diabetes and proliferative retinopathy on endothelial cell proliferation estimated on [3H] thymidine incorporation, was lower to that observed with the MO-CM in 20 normal controls but the difference did not reach the statistical level of significance. The basal tumor necrosis factor alpha secretion expressed by monocytes was significantly lower in the MO-CM from Type 1 diabetes patients (median: 0.49, range 0.13-2.86 ng/10(6) monocytes) than in the MO-CM from the control subjects (median: 1.84, range: 0.13-7 ng-10(6) monocytes) p0.02. The increase in interleukin 1-beta and in tumor necrosis factor alpha production after lipopolysaccharide stimulation were similar in the 2 groups. A low basal tumor necrosis factor production per monocyte may contribute to the development of the diabetic complications as it is involved in several cellular regulation processes.

Among high density lipoprotein particles, LpAI particles which contain apolipoprotein A1 alone, appear to be involved in cholesterol transport from peripheral tissues to the liver. The aim of this cross-sectional study was to examine serum LpAI particle concentrations in Type 1 and Type 2 diabetic patients with renal lesions of differing grades, in comparison with normal controls and with nondiabetic patients presenting with chronic renal failure. LpAI concentrations and LpAI-to-apo A1 ratios were increased in Type 1 diabetic patients with normal albumin excretion. In Type 1 and in Type 2 diabetic patients with increased urinary albumin excretion, LpAI concentrations and LpAI-to-apo A1 ratios were found to be not different from those of normal controls. In diabetic and in nondiabetic patients with chronic renal failure, LpAI concentrations were decreased. These abnormalities may contribute to the development of macrovascular complications.

We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system.

Problems raised by diabetes in subjects above 65 years of age are of three kinds: diagnostic, therapeutic and social. Passed the age of 40, there is a regular physiological increase of glycaemia, and this must be taken into account to diagnose diabetes and to set the threshold for therapeutic intervention. The treatment of elderly people has its specific imperatives, due to feeding habits and age-related changes in hepatic and renal functions. The presence of complications, sometimes multiple, explains that the patient often takes several drugs, which increases the risk of interaction between these drugs and oral antidiabetics. The therapeutic objectives must be adjusted to these imperatives, and neither the diabetic... nor his doctor must be afraid of insulin. The social status of elderly patients must not be neglected: the help of private nurses and the training in diabetology of the patient's entourage often permit to postpone the date of institutionalization.

Multiple endocrine neoplasia type 2 (MEN 2) is transmitted as an autosomal dominant trait, with 3 different forms. MEN 2a consists of medullary thyroid carcinoma, phaeochromocytoma(s) and hyperparathyroidism. In MEN 2b, parathyroid hyperplasia is absent, but a Marfan-like syndrome and neuromas of the mucosae are present. In some families, the only manifestation of MEN 2 is a medullary thyroid carcinoma. These 3 forms seem to related to one or several gene(s) located in the pericentromeric region of chromosome 10. The histological lesions of MEN 2a are multifocal, bilateral and associated with hyperplasia (which affects C-cells in the thyroid gland). Screening for familial medullary thyroid carcinoma is based upon plasma calcitonin levels measured before and after a pentagastrin stimulation test. The demonstration of DNA markers near the gene(s) of the disease in chromosome 10 pericentromeric region makes it possible to identify, with good probability, the subjects at risk for the disease. It is only by determining the responsible gene(s) that subjects carrying the hereditary anomaly will be identified directly, without marker assays.

SUMMARY - The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established by intervention studies. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. This review focuses on the consequences of hyperglycemia on the formation of advanced glycation end-products (AGEs), and on the role of AGEs and of their specific receptors (RAGE) in the functional and anatomical alterations of the vascular wall. AGEs are formed during the Maillard reaction by the binding of aldoses on free NH2 groups of proteins, which, after a cascade of molecular rearrangements, result in molecules of brown color and specific fluorescence. Experimental studies have indicated that the binding of AGEs to RAGE activates cells, particularly monocytes and endothelial cells. Activated endothelial cells produce cytokines, and express adhesion molecules and tissue factor. The role of AGEs in increased oxidative stress, and in the functional alterations in vascular tone control observed in diabetes, in part related to a reduction in nitric oxide, is also discussed. The microvascular retinal, glomerular and nerve lesions induced by experimental diabetes in animals are prevented by an inhibitor of AGEs formation, aminoguanidine. The administration in diabetic animals of recombinant RAGE, which hinders AGEs-RAGE interaction, prevents hyperpermeability and vascular lesions. These data suggest a central role of AGEs and RAGE in the development of chronic complications of diabetes.

Resume Avec un test standard 40 ml de sherry (xeres) 12 h et 36 h apres la prise de 250 mg de chlorpropamide, nous avons observe une bouffee vasomotrice faciale (CPAF) chez 34 p. 100 des diabetiques non insulino-dependants (19/56), 10 p. 100 des diabetiques insulino-dependants (3/30) et 7 p. 100 des temoins (2/27). Le CPAF n'etait pas associe chez les diabetiques non insulino-dependants a une plus grande frequence d'antecedents de diabete au l er degre. Des biais de recrutement, des imperfections methodologiques semblent expliquer certains resultats contradictoires de la litterature concernant la prevalence du CPAF chez les diabetiques non insulino-dependants.

The case of a young Type 1 diabetic patient with subcutaneous insulin resistance, causing recurrent ketoacidosis, is reported. Intramuscular and intravenous insulin administration remained effective. After failure of CSII, continuous intramuscular insulin infusion was used during 10 months followed by a combination of insulin and a protease inhibitor aprotinin, with good results. After 18 months' aprotinin therapy, subcutaneous insulin resistance disappeared. The subcutaneous insulin resistance syndrome and the role of aprotinin are discussed.

Results of subtotal thyroidectomy in 36 patients with Graves' disease emphasize the need for strict medical preparation, with the administration of corticoids more particularly, and the technical imperatives required during operation. Analysis of endocrine factors showed that euthyroidism was obtained in 76% of cases with a fairly stable state after 6 months. Hyperthyroidism was rare and developed before the end of the first year. Hypothyroidism, mainly biologic, was frequent during the immediate postoperative period but compensatory hypertrophy of remaining tissue was the usual outcome. It was persistent in 14% of cases, however, but easily compensated by substitutive therapy and a less severe complication than prolonged hyperthyroidism. Biologic hypocalcemia was also frequent but normal levels were reinstituted rapidly. Surgical treatment of Graves' disease is usually effective and rapidly performed, and is particularly indicated when socio-ethnic conditions make medical treatment difficult or impossible.

Medullary thyroid carcinoma is a rare and sometimes hereditary disease. The tumour can be diagnosed and followed up by measuring the amounts of calcitonin it secretes. The prognosis of this cancer largely depends on an early diagnosis and treatment. From the clinical and laboratory (calcitonin assays) data recorded in our department, we have endeavoured to determine the influence of a national multidisciplinary co-operative group (GETC: French medullary study group) on the diagnosis and prognosis of this malignancy. We are able to show that the number of medullary thyroid carcinomas detected (principally in their familial forms) has increased by 141 per cent after the GETC was created. Calcitonin levels at the time of diagnosis are significantly lower (P less than 0.05) in familial cases, which reflects an early detection. The same applies to post-operative calcitonin levels (P less than 0.005), so that in the long run a better prognosis can be expected. It seems therefore that together with a better knowledge of this cancer and its detection, the setting up of a national multidisciplinary co-operative group results in a better clinical and therapeutic approach of these patients, and particularly of the familial cases of medullary thyroid carcinoma.

Diabetes mellitus is associated with a high prevalence of atherosclerotic and microvascular disease (31). Platelets may play a part in the development of these vascular complications. Hyperag-gregability is frequently reported in diabetes mellitus (1, 2, 7–9, 11, 16, 20, 27). Some factors which could contribute to platelet hyperactivity have been studied.

The management of hyperthyroidism due to inappropriate secretion of TSH (IST) includes agents that selectively suppress TSH hypersecretion both in patients with TSH-secreting tumor [neoplastic IST (nIST)] in whom pituitary surgery was unsuccessful and in those with selective pituitary resistance to thyroid hormone action [nonneoplastic IST (nnIST)]. Among such agents, somatostatin administration has proven to be effective in blocking TSH hypersecretion, but its short plasma half-life prevented its use in long term therapeutic trials. The recent availability of a potent and long-acting analog of somatostatin (SMS 201-995, Sandostatin) prompted us to study its effects on serum TSH, alpha-subunit, and free thyroid hormone (FT4 and FT3) concentrations in five patients with nIST and three patients with nnIST. During short term SMS 201-995 administration (100 micrograms, sc, three times daily for 5 days) both serum TSH and alpha-subunit levels decreased in all patients with nIST (mean decrements, -86% and -85%, respectively), with concomitant normalization of serum FT4 and FT3 concentrations. In the three patients with nnIST, this treatment lowered serum TSH levels less well (mean decrement, -47%), although serum FT4 and FT3 levels normalized in one patient. Chronic SMS 201-995 (100 micrograms, sc, every 12 h for 1-7 months) treatment in four hyperthyroid patients (two with nIST and two with nnIST) resulted in a steady euthyroid state in both patients with nIST, with restoration of normal visual fields in one patient. In contrast, in both patients with nnIST, escape occurred after 2 weeks of therapy. We conclude that SMS 201-995 administration is effective treatment for patients with nIST, able to suppress TSH hypersecretion from the adenomatous thyrotrophs and, consequently, to restore clinical and biochemical euthyroidism in such patients. On the contrary, the inhibitory effects of SMS 201-995 on TSH secretion in patients with nnIST are weaker and transient.

A retrospective study of 94 patients, who had had doubtful results in the oral provoked-hyperglycemia test, was made after an average period of 23 months. It was found that 26 patients were diabetic, 34 were normal and 34 were still doubtful. The factors which influence the evolution of these cases are the sex, a family history of diabetes (before 60 years of age), and the return to normal weight of obese patients.