Biomedical subjects

G Sassolas

Publications and source records attributed to G Sassolas.

At least 73 records · Page 4Linked to original sources

PubMed1987

Clinical and hormonal effects of a long-acting somatostatin analogue in pancreatic endocrine tumors and in carcinoid syndrome.

Nine patients with pancreatic apudomas (seven gastrinomas, one glucagonoma, one tumor secreting a substance P-like component) and nine with metastasized carcinoid tumors were treated with a somatostatin analogue (SMS 201-995), administered subcutaneously twice daily for 3 days. Treatment was pursued for 2 to 12 months in nine patients in whom SMS was clinically and/or biologically beneficial. In gastrinomas, SMS decreased plasma gastrin in all but one patient, inhibited the residual gastric acid secretion under H2-blockers and improved diarrhea; in the glucagonoma patient, glucagonemia decreased and skin lesions disappeared. In carcinoid syndrome, clinical efficacy was partial and inconstant; daily 5-hydroxyindole acetic acid (5-HIAA) output was slightly decreased. Plasma substance P levels decreased in six patients with initially high concentrations. No antitumoral activity or side effects have been so far evidenced. SMS 201-995 is a useful, well-tolerated agent in secreting pancreatic apudomas and to a lesser extent in carcinoid syndrome, where high-dosage regimens may be required.

Adult↗

PubMed1987

Detection and enzymatic deglycosylation of a glycosylated variant of prolactin in human plasma.

Immunoperoxidase electrophoresis was applied to the plasma of a patient showing a high level of prolactin (PRL) secreted by a pituitary adenoma. Two PRL monomers were detected with an anti-hPRL antiserum: a major 22 kDa form and a minor 25 kDa form. Concanavalin A-Sepharose 4B chromatography revealed that the 25 kDa form was a glycosylated variant of PRL. Incubation of this variant with endoglycosidase F led to its transformation into the 22 kDa form.

Adenoma↗

PubMed1987

Pharmacokinetics of human growth hormone releasing factor (hGRF-44 NH2) in normal men after intravenous administration of a large range of doses.

Three ranges of doses of growth hormone releasing factor (2.5-80 micrograms, 80-320 micrograms and 75-600 micrograms) were intravenously administered to healthy young volunteers in three double blind studies. Serum circulating GRF levels were determined by radioimmunoassay. Experimental concentration curves were fitted, using the extended least squares method, to a biexponential model for the structural model and power function for the variance model. The power variance model, compared to the constant variance model greatly reduced the coefficient of variation of the biexponential parameters. The power of the variance model was estimated to be 1.95. The distribution half-life was 6.6 min and the elimination half-life was 39.0 min (harmonic means). Total clearance was 0.12 +/- 0.01 microgram/l/min. No difference between these parameters was found for the various doses. GRF kinetics was linear established in the range 10 to 600 micrograms which means that elimination was not altered by the increased doses.

Adult↗

PubMed1987

[Plasma variation of atrial natriuretic peptide in central hypervolemia (diurnal or nocturnal) induced by antiorthostatic decubitus at -6 degrees].

Plasma levels of ANP were measured during a 4 hrs head-down tilt at -6 degrees in 5 healthy male volunteers (aged 20-22 M.2). The experiments took place from 8 to 14 hrs, (day), and from 22 to 7 hrs (night). The control period was 1 hr. in a seated position (8 to 9 hrs. for day and 22 to 23 hrs. for night). Blood samples were collected at 9 and 23 hrs. and every 20 min. during the first hours, and every hours thereafter. Electroencephalograms were continuously recorded during night. Our results showed a similar increase in ANP during both experimental conditions. During night there was no correlations between ANP and sleep stages. Finally the differences observed in renal responsiveness to central volume expansion during day or night could not be explained by a difference in renin, aldosterone, vasopressin (previously demonstrated in several studies) or ANP secretion.

Adult↗

PubMed1986

Synthetic human growth hormone releasing factor (h-GRF-I-44-NH2) dose response effect on growth hormone and prolactin secretion in healthy adult men.

The dose-effect relationship of an i.v. bolus of synthetic h-GRF-44 on growth-hormone and prolactin secretion has been studied. Seven healthy adult volunteers received in a random order h-GRF-44 2.5, 5, 10, 20, 40 and 80 micrograms and a placebo. Plasma growth hormone (GH) was determined between 30 min before and 240 min after injection, the area under the curve (AUC) and the peak GH level being used to assess the response. For both parameters a dose-effect relationship was observed. Doses as low as 2.5 micrograms were capable of eliciting a rise in GH plasma levels in few patients. Above 40 micrograms the dose-effect curves tended to plateau, although the decrease in the slope of the dose-effect curve at the peak was more marked. Intersubject variability was large, so precise determination of the minimal effective dose as well as the lowest dose giving a maximal effect was not possible. The available evidence suggests that the i.v. dose of synthetic h-GRF-44 (SR 95228) which is likely to promote GH release into the blood stream in most healthy adults is within the range 40-100 micrograms. In these healthy adults unwanted effects were infrequent with these low doses. Unlike previous experience with higher doses of another synthetic h-GRF-44, prolactin secretion in this study was not affected.

Adult↗

PubMed1986

Clinical studies with human growth hormone releasing factor in normal adults and patients.

The recent availability of human growth hormone releasing factor (hGRF) encouraged thorough investigations of human growth hormone secretion. Moreover it is now possible to put forward a therapeutic application for this hormone. Herein, we report the dose-effect relationship obtained between hGRF and GH response in normal young men submitted to IV administration of doses ranging from 2.5 to 600 micrograms per subject, in three protocols. In some subjects the 2.5 micrograms dose elicited GH secretion as compared with placebo. A highly significant dose-effect was observed (based on GH-AUC and GH-peak) for doses ranging from 5 to 80 micrograms. Responses were identical above 80 micrograms. We conclude that the optimal dose required to elicit maximum GH release with minimal unwanted effects is 80 micrograms in adults. These are related to the dose and observed for doses up to 80-150 micrograms. Subcutaneous administration also induced GH-release, with relationship to the doses used (100, 300 and 600 micrograms per subject). The mean response to the highest dose (600 micrograms) was comparable in timing and magnitude to that obtained with a 100 microgram intravenous dose. Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay and a high correlation was obtained between bioassay and radioimmunoassay. GH was present in blood after hGRF under 3 molecular forms corresponding to little, big and big-big GH with percentages of 50, 30 and 20, respectively. An early and slight increase in prolactin was found to be related to the hGRF doses above 80 micrograms. No change was observed for doses less than 80 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1986

A once-repeated study of nocturnal plasma melatonin patterns and sleep recordings in six normal young men.

The concentration of melatonin was determined, using a sensitive and reliable radioimmunoassay, in plasma samples obtained at 20 min intervals during a 12 hr period (from 20.00 to 8.00) from six normal men. Polygraphic sleep recording was simultaneously performed. Each subject was studied twice at a 1 week interval. For each session, the plasma melatonin profile showed an episodic secretion: a mean frequency of 4.5 peaks and 4.0 troughs per night in the first study and a mean frequency of 4.0 peaks and 3.5 troughs in the second study. The two nocturnal melatonin profiles obtained from each subject were very similar. However, considerable interindividual variation was found (areas under the curve [AUC] from 15.3 to 125 pg X hr/ml). No relationship could be obtained between AUC and body weight. Apparent melatonin half-life calculated from the semilogarithmic plots of the melatonin pattern was 57 +/- 34 min. Chi-square testing revealed that the nocturnal pattern of melatonin levels was not related to sleep stages. Our data do not favor a direct relationship between melatonin secretion and the sleep-waking cycle in humans.

Adult↗

PubMed1986

Investigation of human growth hormone releasing factor in adults.

A dose-effect relationship between human growth hormone (GH) releasing factor (hGRF) and GH response was demonstrated for doses ranging from 5 micrograms per subject (minimal active dose) to 40-80 micrograms per subject (minimal dose for maximal effect). Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay. Unwanted effects were observed for doses equal to or larger than 150 micrograms. Pharmacokinetic parameters were calculated from the immunoreactive GRF plasma concentrations obtained after intravenous injections of various doses. The half-lives were 6.8 +/- 0.4 min and 43.2 +/- 3 min for distribution and elimination phases, respectively. Subcutaneous administration of hGRF was shown to be effective for promoting GH release, with doses higher than those required by intravenous administration. Intermittent intravenous injection of hGRF, at 3-hour intervals, resulted in a decrease in the magnitude of GH response in normal subjects.

Acromegaly↗

PubMed1986

Nocturnal continuous infusion of growth hormone (GH)-releasing hormone results in a dose-dependent accentuation of episodic GH secretion in normal men.

Fluctuations in plasma GH levels have been found in patients with acromegaly who have continuously elevated levels of ectopically produced GH-releasing hormone (GHRH). Likewise, plasma GH fluctuations have been found in normal subjects receiving continuous GHRH infusions. We report the effects of two doses of GHRH, administered by constant infusion, on nocturnal GH secretion in six normal young men. Each received, in random order, 2.5 ng/kg X min GHRH, 15 ng/kg X min GHRH, and 0.15 M NaCl. During both GHRH doses, a highly significant increase in total nocturnal GH secretion was found (P less than 0.001) as well as an increase in GH secretion during different periods of the night. Nocturnal GH secretion was episodic during the GHRH infusions, with an increase in the number and magnitude of the peaks compared to those during the NaCl infusion. Plasma immunoreactive GHRH concentrations plateaued at 1 h during the high dose and at 3 h during the low dose GHRH infusion. Sleep parameters, including total sleep time, sleep latency, and duration and timing of the different sleep stages, were not affected by GHRH infusions. We conclude that GHRH, continuously infused, increases nocturnal GH secretion according to the dose, while the episodic pattern of GH secretion is maintained.

Adult↗

PubMed1986

[Current status of somatocrinin, or GRF, a hypothalamic growth hormone-secreting factor].

UNLABELLED: This short review on GRF is divided into two parts: laboratory findings: Current status of the knowledge on the primary structure of all the GRFs isolated from mammalian sources; structure activity relationships as obtained with synthetic fragments and analogs of GRF; the mechanisms of action of GRF in vitro and in vivo; the localization by techniques of hypothalamic GRF neurons. CLINICAL STUDIES: A summary of past and current clinical studies with hGRF or fragments of hGRF establishing the dose range/effect in normal young adults; pharmacokinetics of hGRF; intravenous, sub-cutaneous and intranasal modes of administration; multi hours perfusions; the use of hGRF alone and in combination with other releasing factors as a diagnostic tool; early clinical results of stimulation of statural growth. Limited bibliography.

Animals↗

PubMed1986

The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors.

Twenty-six out of 400 surgically removed pituitary tumors were identified as gonadotropic adenomas (frequency 6.25%). Morphologic, immunocytochemical, and hormonal characteristics of the gonadotropic adenoma are described. The following morphologic characteristics may suggest the diagnosis: arrangement in cords of cells showing signs of cellular activity, secretory granules, which vary in electron density, form, and size (mean diameter 150 nm) and which are numerous in the extensions near the capillaries, and a rough endoplasmic reticulum arranged in short cisternae. However, owing to the morphofunctional variations from one adenoma to another, we consider that only immunoreactivity with gonadotropin antisera proves the diagnosis. Because the material used to generate the gonadotropin antisera was purified but not pure, for precise characterization of the immunoreactivity, absorption tests with various antigens have to be performed. FSH-LH adenomas (n = 14), FSH adenomas (n = 7), and alpha-subunit adenomas (n = 5) but no LH adenomas were identified in our series. No evident morphologic difference related to the type of immunoreactivity and to the sex was found. Almost all the tumors were large with visual signs caused by suprasellar extension. A recurrence following adenomectomy was noted with a frequency of 12%. The diagnosis of gonadotropic adenoma was considered preoperatively in six out of 26 patients only, on the basis of increased serum gonadotropin levels. Correlations between hormonal levels and pathologic data were established in 17 patients. Seven tumors were associated with high serum gonadotropin levels (FSH and LH: three patients and FSH alone: four patients). In ten cases, the serum gonadotropin levels were normal but serum alpha-subunit assay had not been performed. For the pathologist systematically testing the adenomas with many antisera, gonadotropic adenomas are not as rare as for the clinician. Immunocytochemical studies with gonadotropin antisera and serum gonadotropic determination must be performed in all tumors, especially in those pituitary adenomas that appear nonfunctional.

Adenoma↗

PubMed1986

[Immunohistochemistry of thyroglobulin in the diagnosis of clear cell carcinomas of the cervical region].

6 thyroid gland and 3 cervical lymph node clear-cells carcinomas are investigated by means of indirect immunofluorescence detection of thyroglobulin. Immunofluorescence was positive only in 1 case, which was a primitive thyroid carcinoma. In 7 other cases, its negativity pointed at the metastatic nature of the lesion, from a clear cell carcinoma of kidney (in 4 cases, nephrectomy was very remote, and in 3 cases, the renal lesion was discovered after our examination of the thyroid tumour). One observation showed negative staining reaction, and was a propagation of a parathyroid carcinoma to the thyroid gland. It is concluded that thyroglobulin can be used as an immunohistochemical marker to establish whether a clear cell cervical tumour originates from thyroid gland, or is a metastatic neoplasm.

Adenocarcinoma↗

PubMed1985

[Endocrine pancreatic tumor secreting somatostatin and somatocrinin].

A case of endocrine pancreatic tumour secreting the 2 antagonistic peptides that regulate growth hormone, somatostatin and somatocrinin, is reported. Such tumours are extremely rare and only one other case has been published so far, although pancreatic malignant tumours frequently secrete several hormones. In our patient, the association of diabetes with steatorrhoea, hypochlorhydria, anaemia and biliary lithiasis suggested hypersecretion of somatostatin. Acromegaly, suggested by clinical signs, was confirmed by an excess of growth hormone and somatomedin, and pre-operative somatrocrinin assay confirmed its extra-pituitary origin. Finally, the presence of hyperparathyroidism due to parathyroid gland hyperplasia and of a Recklinghausen disease constituted a multiple endocrine neoplasia syndrome. The significance and implications of this double secretion in vivo are discussed.

Adenoma, Islet Cell↗

PubMed1985

Effects on growth hormone secretion following intravenous and subcutaneous injections of growth hormone-releasing factor (hGRF-44 NH2): comparison of immunoreactive plasma GRF levels.

The effects of subcutaneous administration of three doses of human growth hormone-releasing factor (hGRF-44 NH2 or hGRF) at doses of 100, 300 and 600 micrograms were studied in six normal young men. GH responses obtained with 100 and 300 micrograms were negligible. In contrast, the 600 micrograms dose gave a profile of response comparable in timing and magnitude to that obtained with i.v. hGRF at maximal effect doses (20, 80, 100 micrograms). Plasma immunoreactive hGRF levels (IR-hGRF) were compared after s.c. and i.v. hGRF. Mean maximal plasma concentrations were comparable with s.c. 600 micrograms and i.v. 20 micrograms. Peaks occurred earlier with i.v. hGRF (5 min as opposed to 15 min): however, return to undetectable values was obtained between 90 and 120 min after s.c. or i.v. injections. These data suggest a great loss of the peptide between the subcutaneous space and blood, without delayed absorption. High variability in plasma IR-hGRF concentrations between the subjects after the same s.c. doses was observed.

Adult↗

PubMed1985

Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males.

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.

Adult↗

PubMed1985

Effect of acute intravenous growth hormone-releasing factor on plasma prolactin in short children and patients with growth hormone deficiency.

Four normal subjects and 54 growth hormone (GH)-deficient patients including 43 children with growth failure were given an intravenous bolus of growth hormone-releasing factor (GHRF). Plasma prolactin (Prl) and GH after GHRF were studied. Basal plasma Prl was either normal or elevated and could not predict the GH response to GHRF. A correlation was found, within the group with basal hyperprolactinemia, between basal Prl and the net Prl increase after GHRF. No correlation was found between the net GH and the net Prl increase after GHRF. Plasma Prl was significantly, although weakly, increased after GHRF in the normal subjects.

Adolescent↗

PubMed1985

Diurnal administration of human growth hormone-releasing factor does not modify sleep and sleep-related growth hormone secretion in normal young men.

hGRF (iv 50 micrograms) was administered to 6 normal young adult males at 09.00 and 20.00 h on different days. Nocturnal GH secretion was monitored during polygraphic sleep recordings on both control nights and nights following hGRF administration. Sleep-related GH secretion and sleep parameters were not affected by diurnal hGRF administration.

Adult↗

PubMed1985

[Somatocrinin and children in 1984. Application to the etiological diagnosis of somatotropin deficiencies].

A single acute IV injection (1 microgram/kg) of the synthetic replicate of Somatocrinin (GRF) in 40 children with growth hormone (GH) deficiency induces a marked plasma GH increase, although heterogeneous. Clinical tolerance is excellent. Compared to Propranolol + Glucagon (P + G), GRF induces a better GH response. It also discriminates better idiopathic GH deficiency (n = 13), where mean GH peak = 6.5 ng/ml (3.3 after P + G) from GH deficiency secondary to a brain tumor (n = 24) where mean GH peak = 15.5 ng/ml (5.0 after P + G) GRF induces a slight Prolactin (Prl) increase, more obvious when basal Prl is elevated. However there is no correlation between GH and Prl responses to GRF even with basal hyperprolactinemia. GH response to GRF seems to slowly decrease after radiation therapy. GRF is a new potent, well tolerated secretagogue of GH and improves the diagnostic quality of the etiology of GH deficiency.

Adolescent↗