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Biomedical subjects

P Fossati

Publications and source records attributed to P Fossati.

At least 73 records · Page 4Linked to original sources

A kinetic colorimetric assay of gamma-glutamyltransferase.

We have explored a kinetic colorimetric method for measuring gamma-glutamyltransferase (EC 2.3.2.2) activity in serum, using L-gamma-glutamyl-3,5-dibromo-4-hydroxyanilide and glycylglycine as donor and acceptor substrates. The released product, 3,5-dibromo-4-hydroxyaniline, reacts with 2,5-dimethylphenol to produce a blue quinone monoimine in the presence of ascorbate oxidase (EC 1.10.3.3). This dye has peak absorption at 610 nm, whereas the donor substrate shows negligible absorption throughout the visible spectrum. The reaction can be run with all the reagents in a single working solution with serum as starter, or with the substrate solution as starting reagent. The sample/reagent volume ratio is 1:24. Adaptation of the method to several automated instruments gave good precision in all cases. Comparison with a method in which L-gamma-glutamyl-3-carboxy-4-nitroanilide is the donor substrate showed good correlation of results (r greater than or equal to 0.987). The dynamic range of the method exceeds the upper limits of the reference intervals for men (9-33 U/L) and women (8-25 U/L) by at least 18-fold.

Animals↗

[Catecholamines in the cardiovascular expression of pheochromocytomas. I. Physiological role of noradrenaline, adrenaline and dopamine].

The very diverse clinical expressions of pheochromocytoma are dependent upon type of catecholamine secreted and excreted by the tumor. The role of each of the three amines (adrenaline, noradrenaline, dopamine) is reviewed in relation to physiologic regulation of blood pressure: adrenaline and noradrenaline are pressor hormones and act on almost all blood pressure factors. They possess chronotropic and positive inotropic effects by their action on cardiac beta 1 adrenoceptors, a peripheral vasoconstricting action by interaction with vascular alpha 1 receptors and a direct effect on renin production and tubular resorption of sodium. Inversely, dopamine presents as a hypotensive agent, opposing effects of adrenaline and noradrenaline and possessing numerous sites of action: central hypotensive action on cardiovascular integration structures, inhibitory effect on sympathetic ganglionic neurotransmission, action on specific presynaptic receptors at nerve endings, reducing sympathetic vasoconstrictor tone and finally a direct vasodilator effect. Based on these recent physiologic data the role is discussed of hypersecretion of each amine in the cardiovascular expression of pheochromocytoma. Attention should be concentrated on the nature of hormonal hypersecretion of pheochromocytoma, and a determining role given to the type of catecholamine secreted by the tumor and to the relation between the different amines with respect to the blood pressure symptomatology of pheochromocytoma.

Adrenal Gland Neoplasms↗

[Sensitivity of bone to parathyroid hormone in type I pseudohypoparathyroidism. 6 cases].

The sensitivity of bone to parathormone in pseudoparathyroidism is not well known. Six patients with Type I pseudohypoparathyroidism (4 with Albright's osteodystrophy) had increased alkaline phosphatase levels (5 patients) and radiological signs of periosteal resorption in the hand in one case. All patients had histological signs of increased surfaces of resorption and periosteocytic lacunae, increased osteoid surfaces and relative osteoid volume with no change of the index of osteoid thickness. These changes are identical to those observed in hyperparathyroidism which leads on to the discussion of the role of the increased parathormone secretion induced by the lack of calcium on the remodeling of bone. Our six cases show that there is no bone resistance to parathormone. The diversity of bone changes in hyperparathyroidism, similar to that of primary hyperparathyroidism, is without doubt dependent on the degree of renal insensitivity to PTH through the inactivation of vitamin D.

Adolescent↗

Dopamine-secreting pheochromocytoma: an unrecognized entity? Classification of pheochromocytomas according to their type of secretion.

A pheochromocytoma that exclusively secretes dopamine (DA) rather than predominantly DA among a blend of catecholamines is as yet unreported. Of the 50 patients with pheochromocytoma who have undergone surgery, 32 underwent treatment within the last 5 years (when DA assay has been available). One half of these patients (15/32) exhibited DA secretion either in mixed catecholamines (12 patients) or exclusively (three patients). All three patients with exclusive DA-secreting tumors were normotensive. Without hypertension, the clinical investigation was a diagnostic challenge (unexplained cough or flank mass with inflammatory features). All three tumors were malignant and two were ectopic. Five of the 12 patients with mixed catecholamine-secreting tumors whose secretions included DA were hypertensive. Five other patients had flank mass and one had an unexplained cough. Tumors were rather large, and three of the tumors with mixed secretion were ectopic. Of the 12 patients, seven had tumors that were judged to be malignant. Three patients exhibited a dramatic decrease in blood pressure under alpha-blockade, which was not used in subsequent cases. Predominant or exclusive secretion of DA would explain the lack of hypertension due to its antiadrenergic action that inhibits the vasoconstrictive effects of other amines. Hypertension in patients with pheochromocytoma might depend on the ratio of DA/noradrenaline + adrenaline.

Adrenal Gland Neoplasms↗

[Catecholamines in the cardiovascular expression of pheochromocytoma. II--Study of free urinary catecholamines in 14 pheochromocytomas. Classification of pheochromocytomas according to type of secretion].

Studies were conducted in 14 patients with pheochromocytoma over a 3-year period. Circumstances of detection of these tumors varied greatly and were sometimes misleading, hypertension being an inconstant finding in the clinical history and was not always the predominant feature. Biologic exploration involved assay of excretion of free urinary noradrenaline (NA), adrenaline (AD) and dopamine (DA) using a HPLC technique as well as assay of total methoxy derivatives and urinary vanilmandelic acid. Validity of each assay in the diagnosis of pheochromocytoma could be evaluated and only the total free methoxy derivatives gave false negative results. Hormonal secretion of pheochromocytoma is often mixed, but sometimes predominant or exclusive for a single catecholamine. Relative increases of the different catecholamines, evaluated from the ratios DA/NA and DA/NA + AD, are an important factor since a relation exists between blood pressure induced symptomatology and equilibrium between hypotensive hormone (DA) and pressor amines (NA + AD); 3 types of pheochromocytoma can be described: NA-induced with paroxysmal or permanent hypertension but without typical metabolic and cardiac disorders, and with a very reduced DA/NA + AD ratio during hypertensive crises; AD-induced without permanent hypertension but with a mainly orthostatic hypotension and episodes of cardiovascular collapse following hypertensive attacks and with an AD/NA ratio greater than 1; finally the DA-induced lesion in which hypertension is never associated and manifestations are misleading and atypical with an elevated DA/NA + AD ratio.

Adrenal Gland Neoplasms↗

Phosphate determination by enzymatic colorimetric assay.

A direct colorimetric assay for inorganic phosphate in serum is described. The system is based on utilization of the enzymes, purine-nucleoside phosphorylase and xanthine oxidase, to generate superoxide ions. The superoxide is measured in the presence of an electron mediator compound with 3-(4',5'-dimethyl-2-thiazolyl)-2,4-diphenyl-2H-tetrazolium bromide as the chromogen. The high absorbance of this chromogen between 550 and 660 nm affords useful results with a sample/reagent volume ratio as low as 1:100. A single working reagent is used, and the reaction is complete in 15 min at room temperature. The standard curve is linear for inorganic phosphate concentrations as high as 4.9 mmol/liter. Analytical recovery of phosphate in human sera averages 100%. Within-run precision study gives CV less than or equal to 1.0%. The results of this method compare closely (r greater than 0.99) with those obtained by the semidine method (recommended standard). The method lends itself to automation.

Colorimetry↗

Acute effects of bromocriptine on gonadotropin secretion in polycystic ovary syndrome.

Thirty-two women presenting with polycystic ovary syndrome (PCO) were studied on 3 consecutive days. On day 1, plasma androstenedione, testosterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), estrone (E1), estradiol, serum prolactin (PRL), and PRL response to thyrotropin-releasing hormone were determined. On day 2 the patients were given two placebos at 1-hour intervals; then serum PRL, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and the LH and FSH responses to LH-releasing hormone (LH-RH) were determined. On day 3 the patients were given two 2.5-mg tablets of bromocriptine (BRCR) at 12-hour intervals; then serum PRL, LH, and FSH and the LH and FSH responses to LH-RH were again determined. After BRCR, mean values of basal serum PRL (P less than 0.001), LH (P less than 0.05), and FSH (P less than 0.001) and the FSH response to LH-RH (P less than 0.01) fell with respect to the values determined on day 2. Our group of patients was heterogeneous regarding the effects of BRCR upon the LH response to LH-RH. Of 32 women undergoing the trial, 17 did not respond to BRCR (change of the LH response to LH-RH less than 33% with respect to day 2). They were called "nonresponders." Among the 15 who responded to BRCR, 10 decreased their LH response greater than or equal to 33% ("decreasers") and 5 increased their LH response greater than or equal to 33% ("increasers"). Decreasers had mean values of serum PRL, plasma E1, DHEA-S, and 17-OHP higher than nonresponders (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

Comparative investigations in 26 impotent and 26 nonimpotent diabetic patients.

To determine the causes of diabetic impotence the same investigations were performed in 26 impotent and 26 nonimpotent diabetics. The rates of abnormalities found were almost identical in the 2 groups in regard to Doppler examination of the penile arteries, conduction velocities of the median nerves, latency times of the bulbocavernosus reflex and cystometrograms. Conversely, urine flow rates (24 of 25 versus 2 of 26 patients) and Minnesota Multiphasic Personality Inventory (14 of 23 versus 0 of 14 patients) were almost exclusively abnormal in the impotent diabetics. In addition, inadequate sex-specific attitudes were found in 60 per cent of the impotent diabetic men, which was the proportion found in a carefully selected sample of psychogenically impotent nondiabetic men. The distribution of the abnormalities found suggests that in most diabetic patients impotence results from the addition of a subtle abnormality of the autonomic nervous system in almost every case or psychological and arterial factors.

Adult↗

Hyperprolactinemia and sexual function in men.

Male hyperprolactinemia (HPRL) is known to induce different types of sexual dysfunctions. In order to determine the incidence of HPRL among patients referred for sexual dysfunction, serum prolactin (PRL) was assayed in 1053 clinically idiopathic cases. Among 850 cases complaining of erectile impotence, 10 with marked HPRL (1.1%, PRL above 35 ng/ml) were found, of whom 6 cases were associated with a pituitary adenoma. 17 mild HPRL (2%, PRL 20-35 ng/ml) were also found. Among 124 cases with premature ejaculation, 13 (10%) mild HPRL were found. Serum PRL was normal in 51 cases complaining of an ejaculation without orgasm, and 27 patients exclusively complaining of reduced sexual desire. Our results lay stress on the fact that serum PRL must be assayed in every case of clinically idiopathic erectile impotence. Indeed, 5 of the 10 marked HPRL patients would have been misdiagnosed if we had only assayed this hormone when plasma testosterone was below the normal range. Moreover, in order to shed some light on the mechanisms by which HPRL disturbs male sexual function, the sexual behaviour of 17 markedly HPRL males was compared to their serum levels of PRL and testosterone, first before treatment, then at regular intervals during treatment. Our main conclusion is that impotence cannot be totally explained by a decrease in plasma testosterone, because this steroid hormone was within the normal range 7 of the 16 impotent patients. Moreover, when serum PRL was lowered by bromocriptine, 6 patients recovered their potency before plasma testosterone clearly increased, and in 3 of those patients before it reached the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Medical treatment of hyperprolactinemia.

The current treatment of choice for primary hyperprolactinemia is medical. This is true not only for idiopathic forms, but also for micro- and macroprolactinomas, which are the most frequent causes of this pathology. Although questioned by some authors, the slow evolution of the illness, the rarity of transformation of a microadenoma into a macroadenoma, and the possibility of spontaneous cure cause most authors to favor medical treatment, with which they observe both normalization of gonadal function and tumor regression. By retrospective analysis of 95 hyperprolactinemic patients (72 women and 23 men including 26 cases of suspected microadenoma and 44 macroadenomas) treated with 3 dopamine agonists (bromocriptine, metergoline and CU 32085) between 1975 and 1983, and with the help of large series published in the literature, we have tried to review the present knowledge of this subject. After a quick review of different medications, we will consider their prolactin-suppressing effects, their influences upon gonadal and gonadotropic functions, and their antitumoral action. More specific problems will then be discussed: side effects, resistance, possibility of cure, the evolution of the prolactinoma, the place of medical therapy relative to surgery, and contraception in association with dopaminergics.

Adenoma↗

Treatment of human hyperprolactinaemia with a new dopamine agonist: CU 32085 (mesulergin).

CU 38085 (mesulergin) was given at doses ranging from 0.5 to 5 mg/day to 37 patients with pathological hyperprolactinaemia of varying aetiology. The effectiveness of this drug on the suppression of hyperprolactinaemia and on the recovery of gonadal functions was equivalent to that of bromocriptine previously given to a different group of 83 hyperprolactinaemic patients. Tumour shrinkage during treatment with CU 32085 was ascertained in two cases of macroprolactinoma. Histological examination after adenomectomy revealed extensive peri-vascular fibrosis in both cases. In most patients, the efficient doses of CU 32085 were 5-fold lower than those of bromocriptine. After acute oral administration in 10 previously untreated patients, 0.5 mg of CU 32085 had a more prolonged suppressive effect on Prl levels than 2.5 mg of bromocriptine (approximately 18 vs 12 h). According to this, 0.5 mg CU 32085 once a day was sufficient to maintain Prl levels within the normal range in 16 patients. Side-effects were similar in nature and frequency to those induced by bromocriptine and seemed to be dose-dependent. They can be avoided by slowly increases of dose at initiation of treatment.

Administration, Oral↗