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Biomedical subjects

G Sassolas

Publications and source records attributed to G Sassolas.

At least 37 records · Page 2Linked to original sources
PubMed1996

Relationships between pathological diagnosis and clinical parameters in acromegaly.

From our series of 185 somatotropic adenomas with acromegaly, we found that sparsely granulated adenomas were more frequent (56%) than densely granulated ones. Immunocytochemistry detected growth hormone (GH) plurihormonal adenomas in 68% of patients. GH-alpha-subunit (alpha SU) and GH-alpha SU-prolactin (PRL) were more frequent (38%) than GH monohormonal adenomas (32%). The colocalization of GH and alpha SU in the same cell was obvious in many tumors. In contrast, colocalization of GH and PRL was demonstrated in only 25% of GH-PRL adenomas. The relationships between age, sex, tumor size, GH and PRL plasma levels, granularity, and percentage of GH-, alpha SU-, and PRL-immunoreactive cells were established in 105 acromegalic patients by three statistical methods, mainly by a principal component analysis. Correlations were found between the percentage of alpha SU- and GH-immunoreactive cells, and between densely granulated character and the percentage of GH-immunoreactive cells. Tumor size was not correlated with alpha SU, but was positively correlated with PRL plasma levels. Patients' age and percentage of GH-immunoreactive cells were inversely related to tumor size. Plurisecretion and sparsely granulated aspect are not related to age and tumor size.

Acromegaly↗
PubMed1994

Pharmacodynamics and relative bioavailability of cabergoline tablets vs solution in healthy volunteers.

The effect of formulation on the urinary pharmacokinetics, pharmacodynamics, and relative bioavailability of cabergoline was investigated. Twelve healthy female volunteers, aged 23-35 years, were treated, according to an open, randomized, crossover design, with cabergoline (1-mg single oral dose) both as tablets and as a solution. The two administrations were separated by a 4-week wash-out period. Cabergoline and prolactin were measured in urine and plasma, respectively, by specific radioimmunoassays. Blood samples were collected before and up to 30 days after dosing. Urine was collected before and up to 8 days after dosing. Cabergoline elimination half-lives calculated from urinary data were 68 and 63 h after administration of the tablets and the solution, respectively. Urinary excretion of unchanged cabergoline accounted, on average, for 1.92% (range, 0.14-3.26) and 1.80% (range, 0.67-3.09) of the dose after administration of the tablets and the aqueous solution, respectively. Relative bioavailability of tablets vs solution was 99% (geometric mean with the 90% confidence intervals of 68-144%). Prolactin levels in 10 out of 12 subjects fell below the detection limit of the assay (1.5 micrograms/L) after both treatments. The mean maximum prolactin decrease (ca. 70%) was achieved by 2 or 3 h after dosing; the effect persisted up to 9 days, being completely exhausted 23-28 days after dosing. The analysis of variance performed on the pharmacodynamic effects of the two cabergoline formulations indicated that the percent decreases of plasma prolactin levels were not significantly different for tablets and solution. These results indicate that the pharmacodynamics and relative bioavailability of cabergoline are not influenced by formulation, as tablets or solution.

Adult↗
PubMed1994

Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas.

As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4 +/- 15.4 IU/l to a nadir of 20.3 +/- 11.9 IU/l (-17%, p < 0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

[Strategy of exploration of states of growth hormone hypersecretion].

GH secretion is épisodic in humans. Isolated plasma concentrations thus cannot be used to diagnose excess secretion. Assays on GH secretion require repeat determinations of plasma levels over extended 24 h periods. In so-called conjunctive GH hypersecretion conditions (denutrition, critical states), excessive GH secretion is associated with resistance to this hormone, as indicated by a decrease in plasma IGF-1 concentrations. In contrast, IGF-1 concentrations are high and correlated with GH levels during permanent GH hypersecretion that occurs in acromegaly. Testing for this disorder will vary according to the clinician's objectives.

Acromegaly↗
PubMed1994

Potential therapeutic applications of growth hormone in adults.

Potential therapeutic applications of recombinant human growth hormone (GH) in adults are under investigation in various clinical situations. Patients with GH deficiency represent the more natural indication of replacement therapy with GH; clinical trials have demonstrated a potent metabolic effect with changes in body composition, and improvement in quality of life and physical performances. This treatment is well tolerated since the adverse effects related to fluid retention could be suppressed by dose reduction. In aging, reduction in GH secretion is considered partly responsible for some symptoms and GH treatment can be considered as replacement therapy. In short- and long-term treatments, the effects on body composition and subjective well-being are similar to those obtained in younger GH-deficient adults. In catabolic conditions, nitrogen sparing is demonstrated in most patients. The effect of GH treatment on final outcome is at present unknown.

Adult↗
PubMed1994

Presence of somatostatin receptors negatively coupled to adenylate cyclase in ectopic growth hormone-releasing hormone- and alpha-subunit-secreting tumors from acromegalic patients responsive to octreotide.

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.

Acromegaly↗
PubMed1994

Acromegaly.

Explore the source record for details and available documents.

Acromegaly↗
PubMed1993

Ophthalmic results in patients with macroprolactinomas treated with a new prolactin inhibitor CV 205-502.

Macroprolactinomas are pituitary tumours which have been effectively treated medically since the introduction of bromocriptine. The visual function of 13 patients treated with a new prolactin (PRL) inhibitor CV 205-502 (Sandoz Basle), a potent and selective dopamine D2 receptor agonist, was evaluated. This is the first detailed ophthalmic report of the use of this drug in macroprolactinomas. Patients were enrolled from June 1988 to July 1990 (mean follow up 30 months). Visual function including visual acuity, ocular pressure, and visual fields was regularly controlled. Visual fields (VF) were tested with Goldmann and automatic static perimetry (Vision Monitor). Treatment was globally effective. No modifications of the visual function were observed in nine patients (six normal, three previous VF losses after surgery). In four other patients, visual function dramatically improved (regression of a III paresis, one case; disappearance of a chiasmatic syndrome, three cases). A pituitary necrosis was observed in one case and successfully cured. CV 205-502 seems to be an effective and well tolerated treatment of macroprolactinomas.

Adult↗
PubMed1993

Management of nonfunctioning pituitary adenomas.

Clinically nonfunctioning pituitary adenomas represent one-third of pituitary tumours submitted to surgery. Symptoms consist mainly of visual impairment and there is no evidence of hormonal hypersecretion. Most nonfunctioning pituitary adenomas express genes of glycoprotein hormone subunit(s), and release these hormones in vitro. Thirty per cent of tumours do not synthesize any recognizable pituitary hormones. The first-line treatment is surgery, with the aim of removing as much of the tumour as possible and of reducing visual defects without excessive risks 80% of patients show visual improvement postoperatively. Tumour remnants exist in 30 to 50% of cases; radiation therapy is applied when tumour removal is incomplete. Recurrence of tumour and visual signs and/or an increase in the size of the tumour is noted in about 20% of cases even after radiation therapy. Medical treatment is used when tumour resection is impossible or hazardous. Long-term dopamine agonist treatment in a few cases can induce rapid and partial improvement and small decrease in tumour size in about 15%. Somatostatin analogues can induce an early visual improvement in limited cases, but little visible tumour shrinkage. GnRH analogues have been used in gonadotrophin-secreting tumours; super agonists seem unable to reduce secretion and tumour size.

Adenoma↗
PubMed1992

Melatonin and jet lag: confirmatory result using a simplified protocol.

This study replicates the alleviation of jet-lag with melatonin in a simplified protocol for eastward flight. At 22-n hr (n is the time-lag between the North American departure point and France), subjects took either melatonin (8 mg, n = 15), or placebo (n = 15) on the day of the return flight and for 3 consecutive days. On day 8, self-ratings significantly discriminated between melatonin and placebo for global treatment efficacy, morning fatigue, and evening sleepiness.

Adult↗
PubMed1992

The role of Sandostatin in acromegaly.

Long-acting somatostatin analogues are extensively used for the treatment of acromegalic patients who have not been cured by surgery or for whom surgery is contraindicated or hazardous. Such an analogue, Sandostatin, has been approved for this indication in various countries and to date an overall review is feasible. From the literature and our experience, clinical response of acromegaly is attained in 60% to 70%, with mainly a reduction in headaches, arthralgias, and acral growth. Hormonal response, evaluated on plasma growth hormone (GH) levels, is observed in more than 80% of the patients. In 36% to 45% of the patients, plasma GH levels are reduced to near-normal values, and in 50% of the patients, the percentage of reduction is greater than 50% of pretreatment values. The major source of concern is the occurrence of gallstones during the treatment; its frequency is evaluated differently. From the largest well-documented series, we retain a percentage of 12.5% of newly occurring cholelithiasis and in most cases they remain asymptomatic. Tumor shrinkage is minor in most cases.

Acromegaly↗
PubMed1992

Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass.

Normothermic cardiopulmonary bypass (CPB) is used in cardiac surgery at some institutions. To compare hemodynamic and hormonal responses to hypothermic (29 degrees C) and normothermic nonpulsatile CPB, 20 adults undergoing coronary artery bypass graft and/or aortic valve replacement were studied. Hemodynamic measurements and plasma hormone concentrations were obtained from preinduction to the third postoperative hour. The two groups were given similar amounts of anesthetics and vasodilators. Systemic vascular resistance increased only during hypothermic CPB, and heart rate was higher at the end of hypothermic CPB. Postoperative central venous pressure and pulmonary capillary wedge pressure were lower after hypothermic CPB. Oxygen consumption decreased by 45% during hypothermic CPB, did not change during normothermic CPB, but increased similarly in the two groups after surgery; mixed venous oxygen saturation (SvO2) was significantly lower during normothermic CPB. Urine output and composition were similar in the two groups. In both groups, plasma epinephrine, norepinephrine, renin activity, and arginine vasopressin concentrations increased during and after CPB. However, epinephrine, norepinephrine, and dopamine were 200%, 202%, and 165% higher during normothermic CPB than during hypothermic CPB, respectively. Dopamine and prolactin increased significantly during normothermic but not hypothermic CPB. Atrial natriuretic peptide increased at the end of CPB and total thyroxine decreased during and after CPB, with no difference between groups. This study suggests that higher systemic vascular resistance during hypothermic CPB is not caused by hormonal changes, but might be caused by other factors such as greater blood viscosity. A higher perfusion index during normothermic CPB might have allowed higher SvO2.

Aortic Valve↗
PubMed1991

Surgical outcome and pathological effects of bromocriptine preoperative treatment in prolactinomas.

The case histories of 40 patients with prolactinomas were retrospectively reviewed. Twenty patients treated preoperatively with bromocriptine were compared to 20 untreated patients. The two groups were comparable according to tumor size and sex. All the patients had an immuno-cytochemically confirmed prolactin adenoma. They were operated on by a transsphenoidal approach. Intraoperative findings were studied. The surgical cure rates (serum PRL level less than 30 micrograms/l) of the bromocriptine-treated group were higher than those of the control group, both in microprolactinomas (87.5% vs 50%) and macroprolactinomas (33% vs 17%). This improvement of surgical success rate may not be due solely to bromocriptine. Surgical cure also depends on preoperative serum PRL levels (less than 500 micrograms/l) and tumoral size (less than grade II0). Tumoral tissue remained in all cases. No increase in fibrosis was observed. By inducing tumoral shrinkage, bromocriptine makes surgical removal of macroprolactinomas easier and safer. This tumoral shrinkage could be explained not only by reduction of cell size, but also by decrease in intratumoral hemorrhage. Preoperative bromocriptine treatment does not adversely affect surgical outcome. Moreover, it may be useful in cases of macroprolactinomas with suprasellar extension.

Adult↗
PubMed1991

Somatotropic adenomas without acromegaly.

Seventeen somatotropic adenomas removed from patients without acromegaly were studied. Thirteen of them presented as a prolactinoma with amenorrhea and/or galactorrhea and elevated serum PRL levels. According to basal serum GH levels, the patients were divided into two groups, namely Group I: GH slightly elevated (n = 4) and group II: GH less than or equal to 5 micrograms/l (n = 13). The tumoral GH secretion was proved by immunocytochemistry in all cases and by intratumoral RIA, in vitro study and/or in situ hybridization in five of them. Pathological, clinical and biochemical relationships suggested two anatomoclinical aspects. In group I, the tumors were small, well-differentiated somatotropic adenomas with clinically silent GH hypersecretion. It is probably an early stage of the disease. In group II, the tumors were large with normal GH serum levels. They were poorly differentiated and secreted very low amounts of GH. In nine of them, PRL and/or PRL mRNA expression were also detected. These tumors do not secrete enough GH to increase serum levels and cause acromegaly. The somatotropic adenomas without acromegaly correspond to two anatomoclinical aspects of the disease.

Acromegaly↗
PubMed1991

Pituitary adenomas: automatic static perimetry and Goldmann perimetry. A comparative study of 345 visual field charts.

In a series of 81 cases of pituitary adenoma 345 charts of visual field performed with static automatic perimetry (AP) on the Vision Monitor and Goldmann perimetry (GP) were compared. Generally both methods were equivalent in the detection of chiasmal compression. The charts were divided into two groups: (A) 208 charts and (B) 137 charts according to the number of isoptres investigated: two (V4, 112) or three (V4, 112, 12). In group A the AP was more often altered than the GP, and the difference was statistically significant (p less than 0.001). In group B the GP seemed more effective, but the number of questionable cases was greater and the difference was not statistically significant. When the most internal isoptre of GP was outside the central 30 degrees, AP was more often abnormal (29%) than GP (2.2%), and the difference was statistically significant (chi 2, p less than 0.001). Within the central 30 degrees the GP seemed more often to be altered (23% of cases) than the AP (19.4%), but one-third of the cases were questionable. Within the central 30 degrees both techniques gave identical results and there was no statistically significant difference. The discrepancies between both static and kinetic techniques are an argument for their complementary use.

Adenoma↗