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Biomedical subjects

P Garnier

Publications and source records attributed to P Garnier.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of glucagon on systemic and splanchnic circulation in conscious rats with biliary cirrhosis.

To elucidate the relationship between the haemodynamic changes and glucagon in cirrhosis, we infused physiologic and supraphysiologic doses of this hormone in conscious rats with portal hypertension due to biliary cirrhosis. Cardiac output and splanchnic organ blood flows were measured by the radioactive microsphere method before and 30 min after glucagon infusion at doses of 2, 5 and 10 ng/min. Serum glucagon increased from a basal level of 92 +/- 17 pg/ml (mean +/- S.E.) to 399 +/- 89, 1151 +/- 136 and 2064 +/- 328 pg/ml, respectively, in sham-operated rats, and from 743 +/- 75 pg/ml to 1497 +/- 197, 1583 +/- 356 and 2957 +/- 649 pg/ml, respectively, in cirrhotic animals at 2, 5 and 10 ng/min doses. In both groups, cardiac output did not change after glucagon infusion at 2 and 5 ng/min doses, suggesting that factors other than glucagon are primarily responsible for the systemic hyperdynamic circulation in cirrhosis. Portal tributary blood flow increased significantly after glucagon infusion in sham-operated rats by 34 and 65% at doses of 5 ng/ml and 10 ng/ml, respectively, and in cirrhotic rats by 29% at a dose of 10 ng/ml. However, portal tributary blood flow did not change after glucagon infusion at the physiologic dose of 2 ng/min. This study shows that glucagon infused at a physiologic dose does not increase splanchnic blood flow, although it increases portal tributary blood flow at supraphysiologic doses. The discrepancy between blood glucagon levels and splanchnic haemodynamic responses suggests that glucagon plays only a minor role and that other factors are primarily responsible for the hyperdynamic state of the splanchnic circulation in rats with biliary cirrhosis.

Animals↗
PubMed1989

Receptors and neurohormones in human pituitary adenomas.

In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.

Adenoma↗
PubMed1989

Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone.

Neuropeptides such as vasoactive intestinal peptide, LHRH, or TRH have been found in rat pituitary tissue and could act via paracrine or autocrine actions in this tissue. In this study we investigated whether normal human pituitary tissue and GH-secreting human pituitary adenomas could release somatostatin (SRIH) and GHRH. Fragments from three human pituitaries and dispersed cells from six GH-secreting adenomas (four adenomas were studied for GHRH release and five for SRIH release) were perifused using a Krebs-Ringer culture medium, and the perifusion medium was collected every 2 min (1 mL/fraction for 5 h). GH, GHRH, and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L TRH or SRIH. Both normal pituitaries and GH-secreting pituitary adenomas released SRIH and GHRH. SRIH release commenced 90-180 min after initiation of the perifusion, at which time GH secretion had decreased significantly. TRH stimulated SRIH release from normal pituitary tissue and inhibited SRIH release from adenoma tissue. GHRH was present at the start of the perifusion, but rapidly disappeared. However, SRIH stimulated GHRH release from normal pituitary tissue, but not from adenoma tissue. Significant amounts of GHRH and SRIH were released during the experiments, suggesting their local synthesis. These results indicate that pituitary cells can release hypothalamic peptides. The liberation of these neuropeptides is regulated, and moreover, their regulation differs between normal and adenomatous pituitaries.

Adenoma↗
PubMed1989

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency.

The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below -2 SD in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1-2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

Adolescent↗
PubMed1989

[Neurohormones coming from the normal and tumoral human anterior pituitary. Secretion and regulation in vitro].

Several neuropeptides, classically associated with the hypothalamus have been found in the anterior pituitary and their local synthesis has been hypothesized. Using normal and tumoral human pituitaries we found in the tissue itself different neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries while only stimulatory neurohormones like TRH and GHRH were found in tumoral tissue implying an imbalance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Fragments from normal pituitaries and dispersed cells from GH, PRL and nonsecreting adenomas, were perifused for 4 hours in a Krebs-Ringer medium collected every 2 min and GH, PRL, TRH, GHRH and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L DA, TRH or SRIH. Neuropeptides and DA were characterized by HPLC. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. There was an in situ regulation between SRIH and GH as their secretion profile was negatively correlated, GH secretion decreasing while SRIH secretion was increasing. Moreover the release of TRH was stimulated 5 to 20 folds by DA, while PRL decreased at the same time. Pulses of TRH and SRIH had differential effects on GHRH and SRIH release according to the nature of the tissue as TRH stimulated SRIH release from normal pituitary while it inhibited SRIH release from adenoma. These results indicate that anterior pituitary cells can release neuropeptides which are probably endogenously synthesized and have a local regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

[Determination of EGF receptors (epidermal growth factor) in the placenta and breast tumors].

Receptors for Epidermal Growth Factor (EGF) have been identified in different types of tumors and they are often associated with other characteristics which are related to a bad prognosis. A technic has been established to measure membrane receptors in human placenta, which is appropriate for the study of tumors. Preparations of placental membranes were incubated either with increasing amounts (0.1 to 3.0, 10(-9) M) of EGF labeled with 125I (method by saturation) or with 0.2, 10(-9) M labeled EGF and increasing concentrations (0 to 1.6, 10(-9) M) of cold EGF (method by competition). The KD obtained with both technics are not significantly different: 0.85 and 0.77, 10(-9) M respectively, as well as the maximum binding capacity: 5.9 and 4.4 pmol/mg protein respectively. A preliminary study in breast tumors showed that 2 out of 9 contained significant amounts of receptors (58 and 114 fmol/mg protein). One of these two tumors held both estradiol and progesterone receptors. In the other 7 tumors without EGF receptors only one did not contained any estradiol or progesterone receptors. Further studies are needed to evaluate the relationships between EGF/sex hormone receptor status and the degree of breast tumor malignancy.

Breast Neoplasms↗
PubMed1988

Growth hormone secretion during sleep. I. Comparison with GH responses to conventional pharmacologic stimuli in pubertal and early pubertal short subjects. Effects of treatment with human GH in patients with discrepant measurements of GH secretion.

Growth hormone (GH) was measured in 215 short children (147 males and 68 females, 123 prepubertal, 92 at early pubertal stages), comparing GH responses to classical pharmacologic stimulation tests and spontaneous GH secretion during sleep. GH secretion during sleep, but not GH responses to stimuli, was higher in early pubertal than in prepubertal subjects. The patients were classified into five groups, according to the agreement between GH responses to stimuli and GH secretion during sleep: group I, normal GH-secreting children; group II, completely GH-deficient; group III, partially GH-deficient; group IV, with normal secretion during sleep and low responses to stimuli; group V, with the reverse situation. 30% of the patients were in groups IV and V, both at prepubertal and early pubertal stages. 46 patients of groups II-V were treated with extracted human GH(hGH). The growth rate was enhanced in groups IV and V, to the same extent as in groups II and III. Four points can be concluded: (1) the rise of GH secretion during sleep is an early event at the onset of puberty; (2) the discrepancy between the GH responses to classical stimuli and GH secretion during sleep are of pathological significance; (3) disturbances of GH secretion might be diagnosed by measuring GH secretion during sleep rather than by using conventional stimulation tests; (4) a trial course of hGH treatment could be proposed in patients with both kinds of discrepancies between GH responses to stimuli and GH secretion during sleep.

Adolescent↗
PubMed1988

Endocrine and immunological findings in cryptorchid infants.

In cryptorchid infants, significantly decreased mean levels of plasma testosterone and luteinizing hormone (LH) were found between the ages of 30 and 120 days. The levels of testosterone and LH were significantly correlated. No significant difference was found between infants with bilateral or unilateral cryptorchidism. After 120 days there was no longer any significant difference between cryptorchid infants and controls. No significant change in plasma follicle-stimulating hormone (FSH) was found. These data suggest that subnormal secretion of LH could be the primary abnormality in a proportion of boys with so-called common cryptorchidism. Our studies using LH-releasing hormone and human chorionic gonadotropin stimulation tests in older infants and children agree with the data obtained by measurement of basal plasma hormone levels during the first months of life. Anti-gonadotroph antibodies were found in the sera of approximately 50% of the cryptorchid children and infants studied, using an immunofluorescence technique. A study of 17 mothers and their infants gave concordant results in 16 pairs, 9 with and 7 without antibodies. This lead us to speculate on the possible role of maternal autoantibodies as a cause of partial gonadotrophin deficiency in the perinatal period and thus of testicular maldescent. As cryptorchidism is a syndrome, these findings do not mean that a similar mechanism is operative in all cases. However, these data do suggest that alternatives to the classical anatomical view of the descent and nondescent of the testes should be considered.

Age Factors↗
PubMed1988

[In vitro secretion of somatostatin (SRIH) by human adenomatous somatotropic cells. Relation with somatotropic hormone (GH) release and modulation by thyroliberin (TRH)].

SRIH and GH secretions by GH-secreting adenomatous human pituitary cells were analyzed in vitro in a perifusion system. Of the 13 adenomas studied, 7 secreted SRIH, in variable amounts (50 to 700 pg/ml/2 min., corresponding to 600 10,700 pg for the total experiment. SRIH secretion increased during the perifusion, the highest levels being observed at the end of the perifusion. GH secretion also varied from one adenoma to the other (6 to 500 ng/ml). In most cases, the secretion profiles were negatively correlated, GH secretion decreasing while SRIH secretion was increasing. In the presence of 10(-7) M TRH, GH secretion increased while that of SRIH decreased. The hypothesis of a paracrine and/or an autocrine role for SRIH as well as its possible in situ synthesis are discussed.

Adenoma↗
PubMed1988

[Results of hormonal studies in 23 adolescents with renal failure treated by chronic dialysis].

The hormones regulating growth, growth hormone (hGH), IGF I, sex steroids, thyroxin (T4) and parathormone (PTH) have been measured in 23 adolescents aged from 13.5 to 20 years (14 boys, 9 girls), with chronic renal failure treated with haemodialysis. Growth velocity (GV) was (mean +/- DS) 4 +/- 2.1 cm/year in boys and 1.6 +/- 1.65 in girls, with a bone age of 12.9 +/- 2.4 cm/year. T4 and DHA sulfate (DHAS) differed according to sex (boys: T4 = 70 +/- 4.7 ng/ml; DHAS = 655 +/- 139 ng/ml; girls: T4 = 102 +/- 16.6 ng/ml; DHAS = 118 +/- 35 ng/ml). IGF I, within normal limits, was correlated to bone age and pubertal stage. T4 was negatively correlated to testosterone and SDHA in boys. GV expressed as SD according to bone age was negatively correlated to PTH.hGH deficiency was evidenced in one case, and GV increased under hHG therapy. It is concluded that measuring hormones is necessary in renal failure. Secondary hyperparathyroidism is an inhibiting growth factor. Possible hormonal deficiencies have to be treated.

Adolescent↗
PubMed1988

[Long-term fate of pituitary dwarfs treated with growth hormone].

A questionnaire having been mailed to 50 hypopituitary patients aged 18 to 36 years (m 21.7 +/- 3.4) previously treated with human growth hormone for at least 3 years, 44 answers have been received. The final height is 2.1 +/- 0.9 standard deviations below the average. However 57% of the patients consider it is sufficient. The smallness is felt as a handicap by 20% only of these adults, though 88% had suffered for it during their adolescence. The treatment is retrospectively considered as useful and acceptable by 68%, heavy but useful by 25%, heavy and useless by 7%, without correlation with the results. Only 41% are satisfied with their school achievements. However, more than two thirds of patients had severe school difficulties at the time of onset of the treatment. Actually 75% of the patients are professionally qualified, among whom 36% have achieved high school, and most have an educational level similar to that of their parents or even higher. But 41% only have an employment, 27% are still students and 32% are unemployed. The way of life of the young hypopituitary adults is severely affected: 6 only are married or living with a mate, 11 only write they have occasional sexual experiences, 16 remain completely alone. In contrast, leisure activities are good in more than 90%. A score taking all these data into consideration to evaluate their way of life shows, among the 43 complete answers to the questionnaire, 16% with excellent results, 49% with a rather good social status and 35% with poor final result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Impaired response of growth hormone-releasing hormone (GHRH) measured in plasma after L-dopa stimulation in patients with idiopathic delayed puberty.

In order to investigate the regulation of GH secretion in patients with idiopathic delayed puberty (IDP), either prepubertal (stage P1) or early pubertal (P2), GHRH levels in plasma were measured after stimulation with L-Dopa in a group of 16 patients with IDP. The results were compared to those obtained in 12 patients with constitutional short stature (CSS) at the same stages of puberty, who underwent L-Dopa test for insufficient height. Plasma GHRH levels were measured, after extraction and concentration on C18 Sep Pack columns, by radioimmunoassay using an antibody against 1-40 GHRH, which cross-reacts 100% with 1-44 GHRH. The sensitivity of the assay is 6-8 pg/ml. After L-Dopa intake, the peak of GH was mean +/- SEM 8.6 +/- 1.4 ng/ml in IDP and 12.0 +/- 0.8 ng/ml in CSS (NS). The peak of GHRH after L-Dopa was 41 +/- 10 pg/ml in IDP and 96 +/- 25 pg/ml in CSS (p less than 0.02). A significant (p less than 0.02) decrease of plasma GHRH peak values (mean +/- SEM 17.3 +/- 4.4 pg/ml) was noted in the five patients with IDP whose growth velocity was below -2 SD for their bone age compared to the patients with normal growth velocity (mean +/- SEM 75.0 +/- 14.5 pg/ml). These results suggest a hypothalamic dysfunction in patients with IDP, and a relationship between the well-known partial and transitory somatotropic deficiency found in some adolescents having a pubertal delay and their secretion of the releasing hormone GHRH.

Adolescent↗
PubMed1987

Dose-response relationship in the treatment of hypopituitary children with human growth hormone: a retrospective survey.

During the past 15 years, dose-response studies of hGH have been limited to prepubertal patients with complete somatotrophic deficiency, who have usually been treated with hGH three times/week within a dose range of 10-40 IU/kg/year. In such studies a weak positive correlation has been found (r = 0.429, p less than 0.001) with marked important individual variations. Very few or no data have been published regarding the dose-response relationship after the first year of hGH treatment, or when the dose is increased because the growth rate is waning, or during puberty. The present paper reports some data on these issues. A group of 32 young hGH deficient children, whose bone age was 0-4 years, was followed up for at least 3 years with hGH given intramuscularly three times weekly at doses of 12-48 IU/kg/year (mean, 25 +/- 9 IU/kg/year - i.e. approximately 0.15 IU/kg/injection). A dose-response relationship existed during the first year but not during the following 2 years nor for the height gain obtained at the end of the third year of treatment. The results of an increase of the dose of hGH by 33-66% in 13 prepubertal hGH deficient children whose growth rate had decreased after 2-5 years of treatment were fair in 6, limited in 4 and absent in 3, and did not relate to the extent of dose increase. However, this series is too small to allow definite conclusions. The growth rate of 67 adolescents with complete hGH deficiency and normal spontaneous puberty was close to the normal mean in the 45 males but much less in the 22 females. Although the least favourable results came from cases with post-radiotherapy hypopituitarism, the mean total pubertal growth spurt in patients with idiopathic hGH deficiency was also below the average, mainly in the girls, and with a large range of individual variation. An important fact was that bone age increased more than height age or chronological age in these hypopituitary pubertal patients. No dose-response relationship was found in this group, within a limited range of doses (40 patients receiving 16-20 IU/kg/year injected three times weekly, 19 receiving less than 16 IU/kg/year and 8 receiving more than 20 IU/kg/year). It may be concluded that in prepubertal hypopituitary children, hGH at a dose of approximately 20 IU/kg/year at the onset of treatment is probably appropriate. The lack of a dose-response relationship after the first year of treatment suggests that higher initial doses should be avoided.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Height↗
PubMed1987

Comparison of growth hormone response to growth hormone-releasing factor 1-44 according to the combined study of sleep secretion with the responses to pharmacologic stimuli.

The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.

Adolescent↗
PubMed1986

Plasma growth hormone releasing factor levels in children: physiological and pharmacologically induced variations.

Plasma growth hormone releasing factor (GHRH) was measured by RIA in the plasma of 41 children with constitutionally short stature. Basal plasma GHRH was 51 +/- 10 pg/ml. L-Dopa induced a 2-fold increase in circulating GHRH 30-45 min before the elevation of GH. A positive correlation (p less than 0.005) was found between the peak of GH and GHRH during the dopaminergic stimulus. On the opposite, the secretion of GH induced by amino acids or clonidine is not preceded by an elevation of plasma GHRH. When a release of GH appeared after the insertion of the venous catheter alone, probably due to the stress, it was preceded by a rise of plasma GHRH. In four sleeping adolescents during the night no relationship was found between the peaks of plasma GHRH and the peaks of GH secretion. These results suggest that the various stimulations of GH secretion used for investigations of a short stature do not act in the same way at the hypothalamo-pituitary level.

Amino Acids↗
PubMed1986

Relationship of plasma growth hormone-releasing hormone levels to pubertal changes.

Basal plasma GH-releasing hormone (GHRH) concentrations were measured by RIA in 180 normal subjects (93 boys and 87 girls between the ages of 8 and 18 yr). Every subject was in good health and between -2 and +2 SD for height. Fourteen boys with delayed puberty also were studied. Plasma GHRH concentrations were higher during puberty than before it. At midpuberty, the mean GHRH levels in girls was 159.1 +/- 28.5 (+/- SEM) pg/ml, approximately 5-fold higher than the level in prepubertal girls (30.3 +/- 4.3 pg/ml). The mean plasma GHRH in midpubertal boys (101.4 +/- 11.5 pg/ml) was approximately 2-fold higher than the level in prepubertal boys (48.1 +/- 5.2 pg/ml). The GHRH levels in boys with delayed puberty more closely resembled those in boys at a similar pubertal stage than those in boys of similar chronological age. The dramatic rise in plasma GHRH levels during puberty suggests a role for this peptide in the adolescent growth spurt. Moreover, these data indicate that GHRH levels during adolescence may be a marker of the patient's pubertal development.

Adolescent↗