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M Cappa

Publications and source records attributed to M Cappa.

At least 73 records · Page 4Linked to original sources
PubMed1995

The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects.

Hexarelin (Hex) is a new synthetic hexapeptide with potent growth hormone (GH)-releasing activity in both animals and men. We evaluated the GH response to a maximal dose of Hex (2 micrograms/kg iv) and GH-releasing hormone (GHRH) (1-29, 1 microgram/kg iv) in 45 short normal children (24 males and 21 females, age 5.9-14 yr, 24 prepubertal and 21 in Tanner stage 2 or 3 of pubertal maturation), in 10 prepubertal obese children (7 males and 3 females, age 7.5-12 yr), and in 5 subjects with organic hypopituitarism (4 males and 1 female, age 8.4-21 yr). In 5 male subjects with constitutional growth delay (age 12.0-13.7 yr), the GH response to Hex was reevaluated 1 week after priming with testosterone enanthate (100 mg im). In all short normal children Hex caused a prompt and clear-cut increase of serum GH concentrations, with peaks occurring between 15-30 min from injection. The GH response to Hex was significantly higher than that observed after GHRH and was not different between males and females or between prepubertal and pubertal subjects. Priming with testosterone resulted in an increased GH response to Hex in all 5 subjects studied. No GH increase was observed in the hypopituitary subjects after either GHRH or Hex administration. In the obese children the GH responses to GHRH and to Hex were significantly lower than in the prepubertal children. Also, in the obese, the GH response to Hex was significantly higher than that observed after GHRH. In all short normal and obese children, but not in the hypopituitary subjects, Hex administration caused a slight but significant increase from baseline of both cortisol and PRL concentrations that returned to the baseline values within 2 h. None of the subjects experienced adverse side effects after Hex administration. This study shows that, in short normal and obese children, Hex is a potent GH-releasing stimulus with potential clinical utility.

Body Height↗
PubMed1995

The effect of hexarelin on growth hormone (GH) secretion in patients with GH deficiency.

Hexarelin (Hex) is a new synthetic hexapeptide with potent GH-releasing activity in both animals and men. We evaluated the GH response to maximal doses of Hex (2 micrograms/kg, iv) and GHRH-(1-29) (1 microgram/kg, iv) in 15 children (11 boys and 4 girls, aged 6.0-17.3 yr) and 4 adults (3 men and 1 woman, aged 20.2-30 yr) with GH deficiency (GHD). GHD was idiopathic in 8 patients and associated with pituitary stalk interruption syndrome in 8, with a pituitary cyst in 2, and with empty sella syndrome in 1. In 11 patients, GHD was isolated, whereas in 8, it was associated with other pituitary hormone deficiencies. Forty-five short normal children (24 boys and 21 girls, aged 5.9-14 yr) served as controls. In patients with idiopathic GHD, the GH response to Hex was similar to that observed in short normal children, and it was significantly higher than the response to GHRH. In the patients with GHD associated with anatomical abnormalities, the GH responses to GHRH varied from normal to absent. Among these subjects, only 1 patient with a pituitary cyst had a sizable GH response to Hex, whereas in all others, the GH response to Hex was absent or blunted compared with those in the short normal children and the patients with idiopathic GHD. In all patients except those with associated ACTH deficiency, Hex administration caused a slight, but significant, increase in cortisol concentrations. This study shows that Hex stimulates GH secretion in patients with idiopathic GHD. The inability of Hex to stimulate GH secretion in patients with hypothalamic-pituitary disconnection strongly supports the concept that in humans, the GH-releasing effect of GH-releasing peptides is mediated by the hypothalamus.

Adolescent↗
PubMed1994

Interaction of free fatty acids and arginine on growth hormone secretion in man.

We studied the interaction between free fatty acids (FFAs) and arginine (ARG) on basal and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in 14 normal subjects. Compared with placebo, ARG induced a significant increase of GH secretion (334.0 +/- 157.5 v 36.9 +/- 27.6 micrograms/L/h, P < .05). The increased levels of FFAs (1.9 +/- 0.4 mEq/L), obtained by the infusion of a lipid-heparin emulsion, abolished the effect of ARG (55.8 +/- 45.6 v 334.0 +/- 157.5 micrograms/L/h, P < .05). GHRH-induced GH secretion was potentiated by ARG (2,009.9 +/- 463.2 v 922.0 +/- 244.4 micrograms/L/h, P < .05) and suppressed by lipid-heparin infusion (106.2 +/- 28.3 v 922.0 +/- 244.4 micrograms/L/h, P < .01). Moreover, the lipid-heparin infusion inhibited the potentiating effect of ARG on the GHRH-induced GH increase (527.9 +/- 113.6 v 2,009.9 +/- 463.2 micrograms/L/h, P < .01). These results confirm the strong inhibitory effect of FFAs on GH secretion, showing that they are even able to inhibit the potentiating effect of ARG on the GH response to GHRH. Since ARG likely acts via inhibition of hypothalamic somatostatin release, the inhibitory effect of FFAs on GH secretion could take place directly at the pituitary level and/or at the hypothalamic level, counteracting the effect of ARG.

Adult↗
PubMed1994

Final height after growth hormone therapy in non-growth-hormone-deficient children with short stature.

We report the effect of growth hormone (GH) treatment for 4 to 10 years in 15 prepubertal non-GH-deficient short children (10 boys, 5 girls, aged 7.4 to 13.2 years). In 7 patients, GH was administered at a dosage of 0.5 U/kg per week (group 1: 4 boys, 3 girls) and in 8 patients (group 2: 6 boys, 2 girls) at a dosage of 1.0 U/kg per week. After the first year, mean linear growth velocity had significantly increased in both groups. The increase in growth velocity was sustained during the first 4 years and then declined to pretreatment values in the majority of subjects. Treatment with GH did not induce an earlier onset of puberty, but there was a tendency toward faster skeletal maturation. The mean final height standard deviation score (SDS) was similar in the two groups and was significantly higher than the height SDS for chronologic age before treatment, but it did not differ from mean pretreatment predicted adult height SDS nor from mean target height SDS in both groups. Final height was significantly correlated with target height in both groups. These preliminary observations indicate that GH treatment does not generally increase final height over target height in short non-GH-deficient children.

Adolescent↗
PubMed1994

High dose immunoglobulin IV treatment in adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is an inborn error of peroxisomal metabolism characterised by progressive demyelination of the central nervous system and by hypoadrenalism. The biochemical defect of ALD results in an impairment in degradation of very long chain fatty acids (VLCFA) with their accumulation in plasma and tissues. Many therapeutic approaches have been tried. Recently, a restricted diet and glycerol trioleate/erucic (GTOE) supplementation have shown normalisation of VLCFA plasma levels, although they are not effective in altering the clinical course of X-linked ALD. The preliminary results are presented of a twelve month trial of immunomodulation by intravenous high-dose immunoglobulins in six patients, mean (SD) age 10.48 (2.8) affected by X-linked ALD, on VLCFA restricted diet plus GTOE supplementation therapy. Six patients aged 9.30 (1.5) with similar clinical characteristics and on the same restricted VLCFA regime of GTO/GTE therapy were studied as the control group. After two months VLCFA levels fell to normal values and remained so for all patients throughout the study. These data show that immunoglobulins are not able to arrest the progression of the disease. The MRI and clinical symptoms deteriorated to the same extent in both groups.

Adolescent↗
PubMed1994

Intravariceal pressure measurement in cirrhotic patients: is it a reliable technique?

The aim of the present study is to evaluate in both "in vitro" and clinical conditions the reliability of the method for measuring the oesophageal varices pressure by means of a sclerosing needle. The perfusion system was validated "in vitro", comparing the tracings obtained with two different perfusion apparatus, with two different perfusional agents and with the needle either completely or partially inserted in a venous catheter perfused with saline solution, either in the same direction as the flow or the opposite one. The clinical validation was conducted on 14 cirrhotic patients with II to IV grade oesophageal varices according to Dagradi's classification. During endoscopy, the intravariceal and oesophageal pressures were measured using a sclerosing needle, perfused with hydrosoluble contrast medium. Once the intravariceal pressure measurement was completed, an X-ray film of the chest was performed. The data were evaluated considering the absence of visible contrast medium as evidence of correct intravariceal needle position, and the presence of a roundish image as evidence of paravariceal insertion of the needle. The presence of respiratory oscillations and intravariceal pressure values were verified in manometric tracings and were compared with radiological findings. The "in vitro" tests showed no differences in the pressure recording obtained using different pumps, different perfusion agents and with different manners of inserting the needle. Only twenty-eight of the manometric recordings were considered adequate for evaluation in clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices↗
PubMed1993

Effect of the enhancement of the cholinergic tone by pyridostigmine on the exercise-induced growth hormone release in man.

We have evaluated the effect of pyridostigmine (PD), a cholinergic agonist, on the growth hormone (GH) response to physical exercise (EXC) in nine healthy volunteers. PD administration and EXC caused a similar increase of GH secretion to mean (+/- SE) peak values of 5.3 +/- 0.9 and 6.5 +/- 1.2 micrograms/l, respectively. Pretreatment with PD caused a significant augmentation of the EXC-induced GH release evaluated both as maximum peak (13.5 +/- 2.1 micrograms/l, p < 0.01 vs EXC) and as area under the secretory curve (EXC = 292.6 +/- 41.9 micrograms.min.l; PD + EXC = 587.3 +/- 68.9 micrograms.min.l, p < 0.005). The action of PD on GH secretion was additive to that of EXC since the sum of the GH responses to PD and EXC was not significantly different from the response obtained during PD + EXC. Whether PD and EXC act through a common final pathway, i.e. inhibition of endogenous somatostatin release, or the EXC-induced GH secretion involves stimulation of endogenous GHRH remains matter of investigation.

Adult↗
PubMed1993

Growth hormone response to oral clonidine test in normal and short children.

We evaluated the growth hormone (GH) response to an acute clonidine test (0.15 mg/m2 po) in 30 normal prepubertal children (stature between the 3rd and 97th centile), in 29 short children (stature < 3rd centile for age) with height velocity (HV) > 10th centile and in 20 short children with HV < 10th centile. The three groups had comparable chronological ages. After clonidine administration mean peak GH levels were similar in the three groups (19.4 +/- 9.8, 17.7 +/- 8.8 and 14.6 +/- 8.9 micrograms/l, mean +/- SD, respectively). By choosing 10 micrograms/l as the limit for a normal response we found that stimulated GH levels had a sensitivity of 50% and a specificity of 83% in identifying children with suspected GHD (short children with subnormal HV). The diagnostic accuracy was almost superimposable, for cut-off values of 10 and 12 micrograms/l. Eight of the 10 children with subnormal HV and a GH peak < 10 micrograms/l had a GH peak < 10 micrograms/l also after a second stimulation test. Six of the 29 short children with normal HV had a GH peak < 10 micrograms/l. Only one of them had a GH peak < 10 micrograms/l after a second stimulation test. Five of the normal children had peak GH levels < 10 micrograms/l. These results indicate that HV is a useful variable to predict the GH response to an acute GH stimulus, since the great majority of children with a normal growth rate had a normal GH response to at least one stimulation test.

Body Height↗
PubMed1993

Growth hormone (GH) response to combined pyridostigmine and GH-releasing hormone administration in patients with Prader-Labhard-Willi syndrome.

We evaluated the GH response to combined administration of pyridostigmine (PD), a cholinergic agonist, and GH-releasing hormone (GHRH) (60 mg PD given orally 60 min before the GHRH bolus) as well as baseline IGF-I concentrations in 10 patients (5 males and 5 females, age 6.0-24 years) with Prader-Labhard-Willi (PLW) syndrome, 8 prepubertal obese children (4 males and 4 females, age 5.6-12.0 years) and 9 prepubertal short normal children (7 males and 2 females, age 8.0-12.8 years). Mean GH responses to PD+GHRH were significantly lower (p < 0.0001) in the PLW patients (13.8 +/- 3.3 micrograms/l) than in the short normal children (52.2 +/- 9.0 micrograms/l) and similar to those of the obese children (14.3 +/- 3.2 micrograms/l). Mean serum IGF-I levels were significantly lower (p < 0.05) in the PLW patients (117.5 +/- 26.4 micrograms/l) than in the obese (329.3 +/- 88.0 micrograms/l) and the short normal children (214.3 +/- 38.3 micrograms/l). Two of the PLW patients had absent GH responses to PD+GHRH associated with subnormal IGF-I concentrations, indicating pituitary GH deficiency. When these 2 cases were excluded from the statistical calculation, mean peak GH responses to PD+GHRH remained significantly lower (p < 0.0001) in the PLW patients (17.1 +/- 3.0 micrograms/l), while their mean serum IGF-I concentrations (143.4 +/- 71.5 micrograms/l) were not significantly different from those of the other two groups. These results indicate that patients with the PLW syndrome have a reduced or absent GH secretory reserve associated in some cases with low levels of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pyridostigmine potentiates growth hormone (GH)-releasing hormone-induced GH release in both men and women.

It has been recently reported that pyridostigmine (PD), an indirect cholinergic agonist, probably acting via inhibition of hypothalamic somatostatin, potentiates the GH-releasing hormone (GHRH)-induced GH rise in men, but not in women. The aim of this study was to verify the sex-related, if any, GH response to GHRH (1 microgram/kg, i.v., as a bolus) both alone and preceded by two different doses of PD (120 mg, group A, and 60 mg, group B, given orally 60 min before GHRH) in a large group of volunteers (36 women, aged 18-35 yr, and 48 men, aged 18-35 yrs). In group A, 120 mg oral PD potentiated the GH response to GHRH in both men [area under the curve (AUC), 2579.3 +/- 264.5 vs. 806.2 +/- 99.7 micrograms/L.h; P < 0.00001] and women (AUC, 2273.2 +/- 248.7 vs. 792.6 +/- 72.7 micrograms/L.h; P < 0.00001). Similarly, in the group B, 60 mg oral PD potentiated the GH response to GHRH in both men (AUC, 1929.6 +/- 157.2 vs. 568.2 +/- 81.3 micrograms/L.h; P < 0.01) and in women (AUC, 1655.9 +/- 146.9 vs. 738.2 +/- 105.7 micrograms/L.h; P < 0.01). The GH responses to GHRH, both alone and after 120 and 60 mg oral PD, did not significantly differ in men and women. No sex-related difference was observed in the cholinergic side-effects (mild abdominal pain and muscle fasciculations) that occurred in nearly 30% of the subjects. In conclusion, our results clearly show that there is no sex-related difference in the potentiating effect of PD on GHRH-induced GH release, ruling out the suggestion that women have increased cholinergic activity, leading to reduced somatostatinergic tone.

Adolescent↗
PubMed1993

Somatotropic function in short stature: evaluation by integrated auxological and hormonal indices in 214 children. The Italian Collaborative Group of Neuroendocrinology.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height, < or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values, > or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values, > or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured. According to their GH secretory status, children were grouped as follows: group I, 154 subjects with normal spontaneous and stimulated GH (43 slow-growing and 111 normally growing); group II, 39 subjects with low spontaneous, but normal stimulated, GH (27 slow-growing and 12 normally growing); group III, 18 slow-growing subjects with low spontaneous and stimulated GH; and group IV, 3 subjects with normal spontaneous, but low stimulated, GH. The following conclusions were drawn. 1) Forty-five slow-growing subjects (21% of the total sample) had GH deficiency; 27 (12.6%) belonged to group II (with a preserved GH pituitary reserve, denoting a hypothalamic dysfunction) and 18 (8.4%) to group III (with a reduced GH pituitary reserve). 2) Forty-three slow-growing children in group I had normal GH secretion but low mean IGF-I, which may indicate nutritional problems or a biologically hypoactive GH molecule. 3) The remaining 111 subjects in group I (52%), with normal growth rate, but low mean parental height, were considered as having familial and/or constitutional short stature. GH responses after pyridostigmine plus GH-releasing hormone were normal in all children with a normal growth rate. These findings show that besides clinical evaluation, the assessment of spontaneous GH secretion, GH pituitary reserve, and IGF-I concentration allows proper pathophysiological characterization of short stature. By this approach, the frequency of GH deficiency in our sample was higher than commonly thought.

Adolescent↗
PubMed1992

Further delineation of the Simpson-Golabi-Behmel (SGB) syndrome.

The Simpson-Golabi-Behmel syndrome is an X-linked condition characterized by pre- and postnatal overgrowth, "coarse" face, postaxial polydactyly, midline defects, and psychomotor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome.

Abnormalities, Multiple↗
PubMed1992

DNA restriction fragment analysis of the somatostatin gene in familial isolated growth hormone deficiency type I.

The somatostatin (SST) gene was analyzed to detect possible molecular variations in subjects with familial isolated growth hormone deficiency type I (IGHD I). No gross alterations in restriction fragments were observed with 18 used enzymes. The association with two RFLPs closely linked to the SST gene was also negative, adding weight to the evidence that the SST gene is not involved in the etiology of IGHD I. The nucleotide variability of a 23-kb DNA segment containing the SST gene and its flanking sequences was studied by restriction analysis of a sample of 19 Italians. The data suggest that approximately 1 in 400 bp is variant in this region.

DNA Restriction Enzymes↗
PubMed1992

Adrenal steroidogenic defects in children with precocious pubarche.

The occurrence of nonclassical congenital adrenal hyperplasia among children with precocious pubarche is still a matter of debate. We studied the adrenal steroid response to ACTH stimulus (Synacthen, 0.25 mg i.v. bolus) in 26 Italian children (5 boys, 21 girls) who had presented pubic hair, without other signs of virilization, at ages ranging between 0.45 and 8.8 years. The control groups comprised 8 prepubertal children (5 boys, 3 girls) and 12 children at Tanner stage 2 for pubic hair development (1 boy, 11 girls). Two patients were diagnosed as having nonclassical congenital adrenal hyperplasia: 1 due to 21-hydroxylase deficiency, the other due to 3 beta-hydroxysteroid-dehydrogenase deficiency. The remainder, classified as having idiopathic precocious pubarche (PP), had adrenal androgens higher than normal prepubertal children and similar levels to those observed in early pubertal controls. In contrast to a recent report, we confirmed that mild adrenal enzymatic defects can occur in PP, and, consequently, the use of ACTH testing in children with PP seems to be recommended.

17-alpha-Hydroxypregnenolone↗
PubMed1991

Somatostatinergic tone in children on chronic haemodialysis and after renal transplantation.

The role of somatostatinergic tone (SST) in growth hormone (GH) neuroregulation in children with chronic renal failure (CRF) and short stature (mean height standard deviation score -3.47) was investigated. Ten children (9 males, 1 female), mean age 13.4 years (range 8-17 years), five with renal transplants (TP) and five on chronic haemodialysis (HD), underwent three separate investigations: (1) measurement of spontaneous GH secretion: (2) measurement of GH after infusion of GH releasing hormone (GHRH); (3) measurement of GH following treatment with pyridostigmine bromide (PD) and subsequent infusion of GHRH. All patients showed normal or exaggerated spontaneous nocturnal GH secretion (mean concentration values ranging between 3.8 and 19.07 ng/ml). In four of ten patients GHRH was not able to cause an increase in GH levels (mean peak GH 7.35 +/- 2.05 ng/ml) while PD pretreatment reinstated the GH response to GHRH (mean peak GH 55.25 +/- 17.23 ng/ml) in these children. In the other patients in whom GHRH-induced GH release was normal or exaggerated (mean peak GH 42.0 +/- 13.8 ng/ml). PD did not potentiate the GH response to GHRH (mean peak GH 54.83 +/- 7.88 ng/ml). These different types of responses were observed both in TP and HD patients. Our data indicate that: (1) PD potentiates the response to GHRH only when GHRH alone is not able to cause GH release, suggesting that SST is already reduced in patients with a normal or exaggerated GH response to GHRH; (2) in CRF patients the SST can be either reduced or increased, at least during the daytime.

Adolescent↗
PubMed1991

The effect of short-term growth hormone or low-dose oxandrolone treatment in boys with constitutional growth delay.

We evaluated the effect of six-month treatment with growth hormone (GH) or low-dose oxandrolone in a group of boys with constitutional growth delay (CGD). Sixteen boys were randomly assigned to two treatment groups. Group 1 received GH (0.6 U/kg/week sc 5-6 times/week) and Group 2 received oxandrolone (0.07 mg/kg po). The boys of the two groups were closely matched for age (13.7 +/- 0.5 and 12.8 +/- 0.4 years) (mean +/- SE), chronologic age/bone age ratio (1.15 +/- 0.04 and 1.16 +/- 0.02), height standard deviation score (SDS; -2.7 +/- 0.4 and -2.5 +/- 0.3) and pretreatment height velocity (HV) (3.7 +/- 0.8 and 4.0 +/- 0.4 cm/year). Other known causes of short stature were excluded in all subjects, and none had taken long-term medication prior to the study. After 6 months of treatment HV increased to 7.5 +/- 0.4 and to 8.1 +/- 0.5 cm/year in group 1 and 2, respectively. Plasma IGF-I concentrations rose significantly after treatment in both groups. Predicted adult height was not significantly affected by either GH or oxandrolone treatment. We conclude that a short-term course of low-dose oxandrolone is as effective as GH to accelerate growth in boys with CGD. Low-dose oxandrolone represents an effective, cheap, and convenient therapeutic approach in boys with CGD.

Adolescent↗
PubMed1991

The growth hormone response to pyridostigmine plus growth hormone releasing hormone is not influenced by pubertal maturation.

We have evaluated the effect of pubertal maturation on the GH response to growth hormone releasing hormone (GHRH), pyridostigmine (PD) and the combined administration of PD + GHRH in a group of short normal children. Fifteen were prepubertal (13 boys and 2 girls, age 5.0 - 12.5 yr), 10 were early pubertal (8 boys and 2 girls, age 11.5 - 16.9 yr in Tanner stage 2-3 of pubertal maturation), and 6 were late pubertal (6 boys and 2 girls, age 13.6 - 17.1 yr in Tanner stage 4-5 of pubertal maturation). All subjects were tested on three occasions with GHRH 1-29 (1 microgram/Kg iv), PD (60 mg po) and PD + GHRH (60 mg PD administered orally 60 min before GHRH). Peak GH levels after GHRH, PD, and PD + GHRH in the prepubertal children (16.0 +/- 2.8, 8.1 +/- 1.3 and 51.1 +/- 5.5 ng/ml, mean +/- SE, respectively) were not different from those observed in the early pubertal (18.4 +/- 2.1, 9.1 +/- 1.9 and 41.2 +/- 5.6 ng/ml, respectively) and in the late pubertal group (14.9 +/- 2.3, 13.1 +/- 2.4 and 42.6 +/- 2.9 ng/ml, respectively). Evaluation of the area under the curve (AUC) also showed no difference in the GH response to GHRH, PD and PD + GHRH between the three groups studied. These results confirm that the combination PD + GHRH is a powerful test to study the GH secretory capacity of the pituitary, and show that pubertal maturation has no effect on the GH response to this test.

Administration, Oral↗