[Immunocytochemistry in the classification of pituitary adenoma. 1300 cases].
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Biomedical subjects
Publications and source records attributed to G Turpin.
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OBJECTIVES: Increased levels of serum lipoprotein (a) in heart transplant patients has been recently shown to be related to early recurrence of coronary artery disease. In order to evaluate the effect of the ischaemic origin of the heart disease we compared lipoprotein (a) levels observed in heart transplant patients who underwent transplantation due to ischaemic heart disease and non-obstructive cardiomyopathy with those in healthy control subjects. METHODS: Serum levels lipoprotein (a) were measured in 62 cardiac transplantation recipients who had a hyperlipidemia. The results were compared with those of 212 control subjects matched for age and who were referred for hyperlipidemia. RESULTS: In the whole population 40 patients had been operated on for coronary heart disease and 22 for idiopathic cardiomyopathy. The two populations did not differ with regard to their cardiovascular risk factors except for the smoking status. The mean Lp(a) values were significantly higher in the subjects with coronary heart disease as compared with those with idiopathic cardiomyopathy (0.33 +/- 0.24 and 0.21 +/- 0.17 mg/dl respectively; p < 0.05). The latter were not different from the control group (0.22 +/- 0.19 mg/ml). We did not find any difference between the two populations concerning the drugs taken by the patients (especially cyclosporine), LDL-cholesterol, creatinine, fasting blood glucose and TSH. CONCLUSION: Our data confirm the relation between coronary atherosclerosis and high lipoprotein (a) levels.
POEMS syndrome is a rare systemic multi-organ disease usually reported in Japanese patients. The clinical course is slow with a 5-year survival of 60%. Death is caused by polyneuropathy and or anasarka. We observed four cases in our ward (all males, aged 39, 57, 54 and 54 years) who all presented at least four characteristic clinical signs. Gynecomasty together with impotency was seen in all patients. All had hypogonadism and borderline hyperprolactinaemia. Hyperoestrogenism was seen in two. In three patients, rare endocrinopathies were part of the POEMS syndrome. One patient had diabetes mellitus. The clinical course was variable and a function of the effectiveness of plasmocyte dyscrasia therapy. Little work has been done on endocrinopathies in POEMS syndrome. In most cases, gonadotrope function is impaired with gynecomasty and impotency in men, amenorrhoea in women. Generally the hypogonadism is hypogonadotropic. Hyperoestrogenism is frequent and prolactin levels are normal or high with an exaggerated response to thyroid releasing hormone stimulation. The aetiology of POEMS syndrome is unknown. Current research is based on an immunologic theory based on the discovery of high levels of interleukin 6 in POEMS patients with or without Castleman's disease. The cytokine would affect the different organs and lead to clinical expression. Corticosteroids are usually effective in most patients, particularly in reducing the oedema and controlling the polyneuropathy.
Several recent studies have confirmed the pathogenic effect of endogenous hypertriglyceridaemia (type IV) on atherosclerosis and thrombosis. Our understanding of the pathophysiological mechanism involved in these hypertriglyceridaemias is constantly improving. Iatrogenic hypertriglyceridaemia can be caused by several classes of drugs including synthetic oestrogens, especially the oestrogen-progesterone contraceptives, and to a lesser extent natural oestrogens taken orally as replacement treatment during menopause, certain hypotensive drugs (non-cardioselective beta-blockers and thiazidic diuretics), corticosteroids, retinoids, cyclosporine, enzyme inductors and iodine produces (by iodine-induced hypothyroidism). All these situations should be recognized and when high lipid levels are observed treatment protocols should be modified or interrupted. Whether associated with a rise or a fall in cholesterol-LDL, such conditions should always taken into consideration due to the increased risk of atherosclerosis, thrombosis or even acute or subacute pancreatitis.
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OBJECTIVES: A measurement of cell DNA content would be highly useful in determining the malignant nature of thyroid tumours in cases without distinctive features such as metastases, capsule invasion or emboli. Abnormal cell ploidy can be recognized with flow cytometry, but it is not known whether such results have diagnostic value. We therefore compared--in a double blind prospective study--the results of flow cytometry and pathologic diagnosis in fresh tumoural and non-tumoural thyroid cells. METHODS: Fifty unselected cold thyroid nodules were obtained from 50 consecutive patients (40 women, 10 men; age 18-80 years; mean 46) who underwent surgery within a 6 month period. Surrounding non-tumoural tissue was also obtained in 46 of them. Cell ploidy and the percentage of cells in each cell phase was determined with flow cytometry for both tumoural and nontumoural tissues. Two pathologists, unaware of the flow cytometric results, independently established the histologic diagnosis according to the WHO classification. RESULTS: The pathologic diagnosis was carcinoma in 7 cases (papillary carcinoma 6, vesicular carcinoma 1) and benign adenomas in 43 (29 macrovesicular, 11 microvesicular, 3 oncocytal). All the non-tumoural tissue samples were diploid. All 7 carcinomas were diploid and 10 of the 43 benign adenomas were aneuploid (4 near-diploid, 3 hyperploid, 1 near-tetraploid, 2 multiploid). The mean proliferation index was increased in 5 diploid tumours. CONCLUSION: These findings confirm that cell ploidy measured by flow cytometry is of no diagnostic value in the thyroid gland. It was also revealed that aneuploidy in adenomas may be related to tissue rearrangements of undetermined prognostic significance.
NHS targets for training clinical psychologists have not been met. Unless training resources are increased there will continue to be a shortfall in service provision. In order to ascertain those areas where training resources are most needed, a postal questionnaire survey of all British clinical psychology training courses was conducted. There was a 73 per cent response rate. Results showed that major areas of need are: (1) increased recruitment of course staff whose major responsibility is training, rather than an over reliance on clinical psychologists who have major NHS responsibilities; (2) greater representation of specialist areas; some priority services such as work with older adults or people with learning disabilities are under-represented; and (3) more equitable pay--not all university courses offer salaries on clinical scales.
The functional study of SRIH receptors was performed in ectopic GHRH-secreting tumors from two patients with acromegaly; patient 1 presented with multiple endocrine neoplasia type 1 with GHRH- and insulin-secreting pancreatic tumors, and patient 2 presented with a multihormone-secreting carcinoid tumor (including GHRH and alpha-subunit secretion, as demonstrated by clinical and immunohistochemical studies). In both cases, plasma GH levels were responsive to octreotide. In patient 2, plasma GHRH and alpha-subunit levels were responsive to octreotide. In vitro perifusion studies of a tumor fragment from patient 1 also showed inhibition of GHRH secretion by SRIH. A high density of specific SRIH-binding sites was visualized by autoradiography in GHRH tumors from both patients. SRIH specific binding was much higher in the GHRH tumors (6.6-8.4 fmol/surface unit) than in the insulinoma (1.9 fmol/surface unit). The binding inhibition constant (IC50) was in the nanomolar range (0.9-3 nmol/L) in the GHRH tumors. SRIH-14 inhibited forskolin-stimulated adenylate cyclase in the GHRH tumors from both patients, but not in the insulinoma. The functional SRIH receptors negatively coupled to adenylate cyclase present in ectopic GHRH-secreting tumors mediate the inhibitory effect of octreotide on GHRH secretion and on previously underrecognized ectopic alpha-subunit secretion from carcinoid tumors.
Each hyperlipidemia patient requires individual management. Treatment choices are thus made for each patient on the basis of evaluation of their overall cardiovascular risk. This evaluation involves four types of characteristics: those which cannot be changed (age, gender), classical lipid and non-lipid risk factors, and finally cardiovascular status with two types of evaluation (clinical status and sub-clinical, atherosclerosis). Three examples are presented here, enabling more precise assessment of lipid risk: syndrome X which shows to what extent risk factors are often associated, combined familial hyperlipidemia which emphasises the importance of family history, and lipoprotein (a). The latter is a risk factor relatively inaccessible to treatment but which enables better evaluation of the risk of the patient and choice of a stricter treatment goal when it is very high.
Plasminogen activator inhibitor type-1 (PAI-1) is a key determinant of the fibrinolytic capacity. Its activity correlates with most of the characteristic features of insulin resistance syndrome, i.e. obesity, high blood pressure and hyperlipidemia. We measured plasma PAI-1 antigen levels in 131 asymptomatic men (aged 44.2 +/- 11 years) who had been referred for hyperlipidemia. Those taking medication and those with a secondary hyperlipidemia were excluded. We confirmed the correlation between PAI-1 levels and the following variables: body mass index, blood pressure, triglyceride concentration, and blood glucose and insulin levels before and after an oral glucose tolerance test. We also found a significant and independent correlation between PAI-1 and the concentration of the hepatic enzymes glutamyl transferase, alanine aminotransferase and aspartate aminotransferase. Mild liver abnormalities (presumably steatosis) may thus be one of the factors accounting for high plasma PAI-1 levels in hyperlipidemic patients.
Severe hypercholesterolaemia include familial homozygous hypercholesterolaemia and certain heterozygous hypercholesterolaemias which become severe, due to spontaneous non-response to treatment or to iatrogenic side effects. Other causes include an associated overload in Lp(a) or uncontrolled atheromatous disease. Surgical treatment has been replaced by iterative LDL apheresis in these severe forms. Mean cholesterol and LDL cholesterol levels can be reduced by 41 to 63% and 49 to 68% respectively with LDL apheresis. In general, HDL cholesterol is protected in selective LDL apheresis. We observed similar decrease for apo B and LDL cholesterol levels. Fifty percent of the Lp(a) was removed in the 3 groups of patients studied.
Menopausal hormone replacement therapy is a physiological rather than a pharmacological approach. Large numbers of cohort studies have now clearly shown that relative coronary risk increases at the menopause in the absence of treatment, in particular regarding an early menopause, and decreases by approximately 50% with replacement therapy, provided the latter is based upon physiological estrogens (all studies on the other side of the Atlantic have involved equine conjugated estrogens). Micronized 17 beta estradiol and in the form of its valerate per os, and percutaneous or transdermal 17 beta estradiol are also available in France. There are beneficial effects on cholesterol fractions, and all the more so if the estrogen is given orally rather than percutaneously or transdermally: decrease in total cholesterol by decrease in the atherogenic fraction LDL-C and apoprotein B, increase in anti-atherogenic fraction HDL2-C and apoprotein A1. There is also a significant fall in lipoprotein (a), a particularly atherogenic lipoprotein if its plasma level exceeds 0.30 g/l and also thrombogenic because of decreased fibrinolysis. Increases in triglycerides are seen only when estrogens are taken orally.
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Hypothyroidism is a classical cause of hypercholesterolaemia. As we sometimes met patients with hyperlipidaemia whose thyroid state was unknown, we carried out a prospective study aimed at evaluating the frequency of hypothyroidism in a population of 1210 hyperlipidemic patients who were referred to our out-patient clinic at the La Pitié Hospital, Paris, for metabolic and cardiovascular assessment. The proportion of subjects with high thyroid-stimulating hormone (TSH) levels was 12, 56 percent, which is distinctly higher than the figures reported in previous studies in patients who were not selected for lipid abnormalities. Among those with high TSH levels, 16 had overt hypothyroidism with a low free T4 level. Analysis of lipid parameters showed that hypertriglycidaemia was frequent and did not confirm the hyperHDLaemia classically observed in hypothyroidic populations. We conclude that screening for hypothyroidism by measuring TSH values is of particular importance in patients with hyperlipidaemia, especially in the group of women over 50 years of age.
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