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Biomedical subjects

P Fossati

Publications and source records attributed to P Fossati.

At least 19 recordsLinked to original sources

[Insulin resistance and polycystic ovary syndrome].

The causes and consequences of the insulin resistance that accompanies the polycystic ovary Syndrome (PCOS) are still controversial. The hyperandrogenism does not appear any more as a causal factor but on the contrary is likely to be a consequence, via the ovarian effects of hyperinsulinism. These are still not clearly understood in their molecular aspects, but their reality is undoubtful in view of some clinical studies which showed an improvement following by the reduction of hyperinsulinism. Therefore, the aetiopathogenic role of the insulin resistance in PCOS becomes more and more obvious but it cannot be split from the likely implication of the intra-ovarian growth factors, and more especially the IGF 1 which could act synergistically with it. Moreover, the presence of LH seems to be still a pre-requisite to the ovarian action of insulin. The therapeutical incidences of these hypothesis are obvious and should improve in the next future the medical management of PCOS.

Androgens

Kinetic colorimetric assay of lipase in serum.

We describe a kinetic colorimetric method for assaying lipase (EC 3.1.1.3) activity in serum by using a natural long-chain fatty acid 1,2-diglyceride. In the presence of colipase, deoxycholate, and calcium ions, pancreatic lipase hydrolyzes the clear substrate solution to produce a 2-monoglyceride, which in turn releases glycerol by the action of a 2-monoglyceride lipase. Glycerol is then assayed by a sequence of enzymatic actions (glycerol kinase, glycerol phosphate oxidase, and peroxidase) that produce a violet quinone monoimine dye with peak absorption at 550 nm. The method features zero-order reaction kinetics, provides a simple and rapid assay with an extended dynamic range, is specific and precise, gives results that correlate well (r greater than or equal to 0.99) with those of methods in which emulsified triolein is the substrate, and lends itself readily to automation. For all these reasons, the method seems highly suitable for routine use in clinical laboratories.

Calcium

Polycystic ovarian disease: contribution of vaginal endosonography and reassessment of ultrasonic diagnosis.

OBJECTIVE: We evaluated the superiority of vaginal ultrasonography (US) on the abdominal US for the diagnosis of polycystic ovarian disease (PCOD). DESIGN: The US pattern of ovaries was prospectively investigated by abdominal US and, whenever possible, by vaginal US. SETTING: Primary care, institutional. PATIENTS: One hundred forty-four women in whom PCOD was suspected on endocrine grounds and 62 other patients presenting with primary hyperprolactinemia (n = 23) or hypothalamic anovulation (n = 39). MAIN OUTCOME MEASURE: Vaginal US allowed a better analysis of the ovarian stroma. RESULTS: The external ovarian features of PCOD were observed by both routes in less than one third of the 144 patients with PCOD. The internal ovarian features of PCOD were much more frequently observed by vaginal US than by abdominal US (polycystic pattern: 66.7% versus 38.1%, P less than 0.05; increased ovarian stroma: 57.1% versus 4.8%, P less than 0.001). In the 62 patients without PCOD, US features of PCOD were observed in less than 10% of them, except for the uterine width/ovarian length ratio less than 1 and the polycystic pattern (abdominal US: 17% and 34%; vaginal US: 11% and 50%, respectively). CONCLUSIONS: An increased ovarian stroma seems to be the most sensitive and specific US sign of PCOD, providing that it can be investigated by vaginal US.

Abdomen

Heterozygous hypobetalipoproteinemia with fasting chylomicronemia.

We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.

Adult

[Gonadotropic adenoma. Clinical and hormonal characteristics].

The main clinical and hormonal features of gonadotropin secreting adenomas (GSA) are reviewed through the literature and our personal data. There is still no agreement about their definition and frequency. The most classical clinical presentation is that of men aged 50 years or more, bearing a large pituitary adenoma, the only biological expression of which is a moderately elevated serum FSH level. Female cases are less recognised and are underestimated because the serum LH and/or FSH elevated levels are not informative in menopausal women. The assay of the alpha subunit may help in these cases. In premenopausal women, few of them having been described so far, the GSA may be revealed by an amenorrhea-galactorrhea syndrome with a mild hyperprolactinaemia which may result from different mechanisms. The absence of gonadal hyperactivity, and, conversely, the frequent hypogonadism associated with GSA lead the clinician to raise some questions: are all GSA able to secret gonadotropins? How is the bioactivity of the LH and/or FSH secreted by GSA? How reliable are the radioimmunoassays routinely used for measurement of LH and FSH in patient's serum? Furthermore, therapeutical management of GSA is still impaired by the lack of documented medical treatments which could control their growth and prevent their recurrence.

Adenoma

Experience of a six-month treatment with sandostatin at increasing doses in acromegaly.

The French Sandostatin/Acromegaly Study Group performed a multicentric, prospective, open-label trial of incremental doses with the aim of obtaining the best antisecretory effect. Forty-two patients (24 women, 18 men) aged 22-71 years were involved, either after unsuccessful surgery and/or radiotherapy (30 patients), or as primary treatment (12 patients). Doses were increased from 3 x 100 to 3 x 500 micrograms/day, according to the results of hormonal investigations (GH profiles and Sm-C) performed each month and for each dose, and tolerability. Four patients dropped out because of major digestive troubles. Recurrent pain at the injection site and minor gastrointestinal disorders were noted in some patients. Asymptomatic gallstones appeared in 4 patients. Carbohydrate tolerance and insulin secretion (determined by diurnal plasma glucose and insulin profiles) were not significantly altered by the various SMS doses. Clinical improvement was determined by the scoring of the symptoms. Mean plasma GH concentrations were significantly reduced for each SMS dose, compared to pretreatment values. Fifteen patients obtained 75% of GH values less than or equal to 2 micrograms/l. In 9 patients the highest dose failed to bring GH below 10 micrograms/l. Sm-C normalized in 17/31 patients. After 6 months of treatment a tumor reduction of 20-50% was found in 7 patients and greater than 50% in 5 patients. We conclude that (1) the tolerability of SMS is compatible with long-term treatments; (2) clinical improvement and biological criteria of efficacy are obtained in 3/4 acromegalic patients treated by SMS, and that (3) some patients are resistant to SMS and the increase in the dose does not improve the result.

Acromegaly

Adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in alcohol dependence disorder. Preliminary report.

A 100-micrograms bolus of synthetic ovine corticotropin-releasing factor was administered intravenously to 10 nondepressed inpatients suffering from an alcohol dependence disorder. The test was performed during withdrawal and after 4 weeks of abstinence. During withdrawal, the plasma cortisol responses of alcoholic patients and 7 control subjects were similar, except for an earlier decrease of cortisol in the former group. However, after 4 weeks of abstinence, the cortisol response was significantly lower in alcoholic patients than in controls. These abnormalities observed during discontinuance of alcohol consumption may reflect adaptive mechanisms of the hypothalamic-pituitary-adrenal activity which may be previously altered by chronic alcohol intoxication.

Adrenal Cortex

Enzymatic assay of magnesium through glucokinase activation.

We describe an improved enzymatic method for assaying magnesium in serum, plasma, or urine. Magnesium participates as an Mg.ATP complex in a reaction catalyzed by glucokinase (EC 2.7.1.2) coupled to an NADP+-dependent glucose-6-phosphate dehydrogenase (EC 1.1.1.49) reaction. The increase of absorbance at 340 nm, due to the NADPH produced, is proportional to the amount of the activated glucokinase, which in turn is related to the concentration of magnesium in the sample. The method is characterized by a zero-order reaction kinetics, affording a simple and rapid assay with good sensitivity and linearity (up to 2.06 mmol/L) and by working solutions that are stable (refrigerated) for one month. The method is reliable, produces test results that compare closely with those of the atomic absorption spectrophotometry (r greater than or equal to 0.99), is suitable for routine work, and lends itself to automation.

Drug Stability

One-step protocol for assays of total and direct bilirubin with stable combined reagents.

We describe an improved colorimetric method for assays of total and direct bilirubin in serum. Bilirubin reacts with diazotized sulfanilic acid in an acidic medium to form a blue azopigment. Total bilirubin is assayed in the presence of reaction accelerators (caffeine, urea, and citric acid), direct bilirubin in their absence. The azo compound so formed is read at the same wavelength (570 nm) in both assays. A sample blank is run in parallel. Standard curves are linear for total and direct bilirubin concentrations up to 513.0 and 256.5 mumol/L, respectively. The method is characterized by (a) use of the same protocol for both assays, i.e., a one-step procedure with short reaction time (5 min at room temperature), and (b) use of a single working solution, which, refrigerated, is stable for one month. The method is reliable, yields results that compare closely with those of the classical Jendrassik--Gróf method, is suitable for routine use, and lends itself to automation.

Bilirubin

Screening heterozygotes for 21-hydroxylase deficiency among hirsute women: lack of utility of the adrenocorticotropin hormone test.

Heterozygosity for 21-hydroxylase deficiency (21-OHD) was investigated in 174 adult hirsute women by using the sum of the incremental responses of serum 17 alpha-hydroxyprogesterone (17 alpha-OHP) and progesterone (P) (delta 17 alpha-OHP + P), 60 minutes after a 0.25 mg intravenous (IV) bolus of synthetic adrenocorticotropic hormone (ACTH). The distribution of 17 alpha-OHP + P in hirsute women was bimodal, allowing two subgroups to be distinguished. In one subgroup including 137 patients, the mode was similar to controls and all values were lower than 3 ng/ml. Thirty-seven (21%) patients constituted another subgroup with values higher than 3 ng/ml and could a priori have been considered as heterozygotes for 21-OHD. However, human leukocyte antigen genotyping provided no conclusive evidence that this subgroup included exclusively heterozygotes for the 21-OHD.

17-alpha-Hydroxyprogesterone

Recovery of ovulatory menstrual cycles under hydrocortisone in two amenorrheic women with isolated corticotropin deficiency.

Two amenorrheic women presenting clinical signs of adrenal insufficiency were shown to have isolated corticotropin deficiency (ICD). LH and FSH were normally responsive to GnRH. The occurrence of this disease during the postpartum and the presence of autoantibodies against corticotropic cells in one case may indicate that ICD was a sequela of an autoimmune hypophysitis. The presence of amenorrhea, while the gonadotroph was not damaged, and the reappearance of ovulatory menstrual cycles under the sole effect of hydrocortisone replacement therapy suggest that cortisol deficiency may by itself alter the gonadal function.

Adrenal Insufficiency

Enzymatic colorimetric method for the determination of inorganic phosphorus in serum and urine.

The performance of an enzymatic colorimetric method for the determination of inorganic phosphorus in serum and urine is described. Phosphate ions react with inosine in the presence of purine nucleoside phosphorylase to form hypoxanthine; this is oxidized by xanthine oxidase to uric acid with production of hydrogen peroxide. The latter is determined with the aid of the chromogen system peroxidase/4-aminophenazone/N-ethyl-N-(3-methylphenyl)-N'-acetylethyl enediamine , the coloured product being measured at 555 nm. This series of reactions is completed in 5 min at 37 degrees C. The test is linear up to 240 mg/l. Analytical recovery in serum averaged 101.2 +/- 1.2% and in urine 101.9 +/- 3.2%. Within-run and between-run precision studies in serum and urine samples gave CVs less than or equal to 4.54% (at 22.0 mg/l). Results obtained by this method agree (r = greater than or equal to 0.983) with the molybdate UV and molybdenum blue methods. Interference by endogenous substances, including organic phosphate, was negligible.

Colorimetry

[Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine].

The biological activity of the natural somatostatin can be quantitatively and qualitatively altered by the substitution and/or the exclusion of some of its amino-acids. The most used synthetic analog, SMS 201-995, has a potent inhibiting effect on GH secretion, but is less effective on insulin and glucagon secretions. It is mainly used in Endocrinology for the treatment of acromegaly. It is also useful for inhibiting the inappropriate TSH secretion from a thyrotroph adenoma. The LH-RH agonists ast essentially by desensitizing the gonadotroph from the endogenous LH-RH. By sub-cutaneous, intra-muscular or nasal route, they allow to inhibit the gonadal functions in some hormone-dependent cancers and in true precocious puberty. More recently, they have been tested for the treatment of gonadotropic adenomas, where they may have sometimes a paradoxical effect. In combination with exogenous gonadotropins, they enhance the control of ovulation and are new valuable tools for IVF programs. Clinical studies with the LH-RH antagonists are just beginning. The long-acting bromocriptine affords a new alternative to the oral treatment of hyperprolactinaemia. Its suppressive effects lasts at least 35 days in normal subjects and 21 days in patients with macroprolactinomas.

Bromocriptine

[Mechanisms of diabetic impotence. 25 cases].

Twenty-five impotent diatetics were investigated by means of nocturnal penile tumescence monitoring, hormone determinations, penile blood pressure measurement, artificial erection test and dynamic cavernosography, bulbocavernous reflex latency time measurement and cortical evoked responses from pudendal nerves. Sexological treatment was then attempted for a better evaluation of the psychogenic element. Penile blood pressure was also measured in 15 non-impotent diabetics and was found to be abnormal as often as in impotent diabetics. The results as a whole demonstrated that impotence was predominantly psychogenic in 9 cases, predominantly organic in 12 cases and mixed psychogenic and organic in 4 cases. Diabetic impotence is often due to several causative factors, as was the case in 12 of our patients. The factors most frequently responsible were psychological (present in 13 cases), neurological (present in 12 cases) and vascular factors (arterial abnormalities in 7 cases, "venous leakage" in 4 cases). Endocrine abnormalities were observed in only 2 cases.

Diabetes Complications

Insulin and HDL-cholesterol metabolism.

Insulin is essential to the physiological regulation of high density lipoprotein (HDL) cholesterol metabolism. It acts directly at the hepatic level by favouring HDL2 to HDL3 conversion (by its action on hepatic lipase). In the peripheral circulation, it induces HDL2 formation by allowing triglyceride-rich lipoprotein catabolism by lipoprotein lipase (LPL) and free cholesterol esterification by lecithin acyl cholesterol transferase (LCAT). In the case of insulin deficiency or peripheral insulin resistance, there is a reduction of HDL cholesterol related to HDL2 decrease, partly due to LPL deficiency. In the case of endogenous hyperinsulinism, there is an intrahepatic disturbance of HDL metabolism partly related to excessive synthesis of VLDL-TG and leading to the decrease of HDL2/HDL3 and enhanced formation of HDL2 TG. When hepatic hyperinsulinism is associated with peripheral insulin resistance, HDL cholesterol decrease is the consequence of both intrahepatic action of insulin and diminution of its peripheric action. Optimized insulin therapy can normalize HDL cholesterol in case of true insulin deficiency. When there is preservation of insulin secretion, HDL cholesterol remains lower than controls. Insulinopenia as well as hyperinsulinism can favour atherogenic lipoprotein disturbances.

Child