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Biomedical subjects

M Bozzola

Publications and source records attributed to M Bozzola.

123 records · Page 7Linked to original sources

Growth hormone bioactivity and immunoactivity in tall children.

In subjects with constitutional tall stature, both low and high GH response to stimulation tests have been observed when measured by commercial kits. To investigate the reason for these conflicting results, we evaluated growth hormone (GH) secretion using different assays as well as GH-binding protein and insulin-like growth factor-I (IGF-I) concentrations in tall children. Serum samples were collected from 22 prepubertal constitutionally tall children, aged 2.87-13.25 years, during two pharmacological tests to evaluate serum GH levels measured by both immunofluorometric assay (IFMA) and the Nb2 cell bioassay. Serum IGF-I values were evaluated by RIA. Circulating low affinity (LA) and high affinity (HA) GH-binding proteins (GHBPs) were evaluated by FPLC gel filtration. Considering the highest serum GH levels as measured by IFMA, the 22 tall subjects were divided into two groups: group A including 16 children with blunted serum GH peak levels (5.78+/-0.68 ng/ml) and group B including 6 subjects with normal serum GH peak values (15.73+/-1.56 ng/ml). No differences were observed in serum GH peak levels as measured by the Nb2 cell bioassay between group A (14.77+/-1.54 ng/ml) and group B (16.03+/-1.96 ng/ml), and between both groups and 11 age-and sex-matched controls (12.25+/-1.19 ng/ml). In group A, the Nb2 cell bioassay/IFMA ratio of serum GH peak levels (0.29+/-0.08) was significantly higher (p<0.05) than in group B (0.07+/-0.01). No differences were found in serum LA-GHBP and HA-GHBP as well as in IGF-I concentrations between the 16 patients of group A and the 6 of group B. Likewise, no difference in auxological parameters was found between the two groups. The biological activity of GH evaluated using the Nb2 cell bioassay is similar in tall children with a low GH response as measured by IFMA in comparison with those with a normal GH response, and is in agreement with both the auxological data and serum IGF-I concentrations.

Adolescent↗

Cyproterone acetate treatment in precocious puberty.

Seven girls with precocious puberty, idiopathic in 6 and associated with the McCune Albright syndrome in 1, were treated with 70 mg/M2/die of cyproterone acetate (CPA) for 11 to 36 months. Before and during treatment clinical parameters (weight, height, bone age, height velocity, prediction of adult height and pubertal development) were evaluated and plasma hormone assays in basal conditions (LH, FSH, 17 beta-estradiol, progesterone, testosterone, PRL, ACTH and cortisol) and after stimulation (LH, FSH, cortisol, GH) were carried out to assess the efficacy and eventual side effects of CPA. The regression observed in the clinical signs of puberty was considered satisfactory and the increase observed in the developmental quotient indicated an improved prognosis for adult height. No symptoms of adrenal insufficiency were observed but an adrenal suppressive effect of CPA was evident from the response to insulin hypoglycemia observed in 4 patients.

Child↗

Growth hormone deficient children treated from before two years old fail to catch-up completely within five years of therapy.

We retrospectively investigated growth response to therapy of 12 patients with idiopathic growth hormone deficiency (GHD), who received GH (0.6-0.7 IU/kg/week) in daily subcutaneous injections from before 2 years of age and for a period of 60 months, in order to ascertain whether very early treatment can enable GHD children to catch-up quickly and completely their initial height deficiency. The onset of therapy was followed in all patients during the 1st year by a significant growth spurt, which persisted, even though attenuated, during the following 4 years. Height deficiency for chronological age (CA) significantly and progressively decreased during the entire study period (from -3.7 +/- 1.9 to -1.0 +/- 1.0 SDS, p < 0.0025), with a cumulative height gain of 2.7 +/- 1.6 SDS. In spite of this catch-up growth no patient attained the target percentile by the 5th year of therapy and their average height (CA) was still lower with respect to the average target height (TH) at the last check-up. Because of the significant bone age (BA) delay still persisting in most patients, a further and complete catch-up growth is likely to occur during the next years of treatment, as suggested by the finding that average height (BA) at the last examination was higher than average TH. It is concluded that: a) in spite of modern therapeutical schedules with daily GH injections and frequent adjustments of doses, GHD children, even though treated from before two years of age, fail to catch-up completely their initial height deficiency, at least by the 5th year of therapy; b) a more prolonged treatment is probably needed to allow them to attain their target percentile. This emphasizes the importance of both early diagnosis and long-lasting treatment.

Body Height↗

Possible role of plasma neurotensin on growth hormone regulation in neonates.

OBJECTIVE: To evaluate secretion of plasma neurotensin (NT) which could be involved as a peripheral signal in growth hormone (GH) regulation, NT release was measured during early postnatal life, a period of striking changes in GH secretion. METHODS: Blood samples were collected from 19 normal full-term neonates on day 5 and at 3 months of age to evaluate plasma NT concentrations by radioimmunoassay, serum growth hormone (GH) levels using an immunofluorometric assay, and serum insulin-like growth factor-I (IGF-I) values by radioimmunoassay. RESULTS: Five day-old neonates showed significantly higher (p < 0.001) mean (+/- SEM) plasma NT levels (83.55 +/- 12.07 fmol/ml) compared with those in 11 prepubertal children and those in 14 adults who were studied as control subjects (13.30 +/- 2.90 and 9.70 +/- 1.10 fmol/ml, respectively). In 5 day-old neonates we observed significantly higher (p < 0.001) serum GH levels (29.53 +/- 3.40 ng/ml) compared with those in the prepubertal children (1.26 +/- 0.28 ng/ml). Five day-old neonates showed significantly lower (p < 0.001) serum IGF-I concentrations (27.01 +/- 0.77 ng/ml) than those in the prepubertal children (210 +/- 25 ng/ml). At 3 months of age, plasma NT levels (59.37 +/- 7.47 fmol/ml) and serum GH values (4.40 +/- 0.60 ng/ml) were significantly decreased (p < 0.001). At the 3rd month of life, serum IGF-I levels (44.88 +/- 4.30 ng/ml) were increased significantly (p < 0.001). CONCLUSIONS: The human neonate showed very high concentrations of NT and GH in comparison with those observed in control subjects. The postnatal rise in IGF-I values is presumed to determine the fall in serum GH concentrations by stimulating somatostatin secretion. Neurotensin could be involved as a peripheral signal in the inhibitory mechanisms mediated by release of somatostatin.

Adult↗

Plasma neurotensin levels in prepubertal children and adults: possible involvement in the regulation of growth hormone secretion.

The present study investigated a possible relationship between plasma neurotensin (NT) and serum growth hormone (GH) levels after GH-stimulation provocative tests in humans. Samples were obtained from twelve prepubertal children and sixteen normal adult volunteers. Basal plasma NT levels were higher in children with growth delay (19.02 +/- 4.01 fmol/ml) (mean +/- SEM) than in normal adults (6.13 +/- 1.1 fmol/ml) (p < 0.001). Basal GH levels in children (1.52 +/- 0.06 ng/ml) were not different from those in adults (0.60 +/- 0.41 ng/ml). After stimulation of GH secretion, NT values decreased when GH peaked, and increased when GH levels diminished. These data suggest that plasma NT levels may be involved in the regulation of GH secretion, as a peripheral signal, probably through modulation of somatostatin release from the median eminence.

Adolescent↗

Modulating effect of growth hormone (GH) on PHA-induced lymphocyte proliferation.

In order to investigate the ability of growth hormone (GH) to modulate lymphoproliferation, peripheral blood mononuclear cells (PBMC) from healthy adults were stimulated with phytohaemagglutinin (PHA) in the presence of increasing concentrations of pituitary (Crescormon) and biosynthetic (Somatonorm and Genotropin) GH (from 0.425 x 10(3) to 501.5 x 10(3) ng/ml) as well as biosynthetic insulin (rhinsulin, Humulin 1 Eli Lilly: from 0.0012 to 20 U/ml). The results obtained show that low doses of GHs and insulin increase lymphoproliferation. In contrast, high concentrations of GHs (8.5 x 10(3) ng/ml) induce a progressive decrease of PHA-induced lymphoproliferation, while insulin does not. No differences in cell viability were observed with and without GHs. Comparable percentages of lymphocytes bearing interleukin-2 receptor (CD25) and comparable values of interleukin-2 (IL-2) pr oduction were found in all conditions tested. Nevertheless, when exogenous recombinant IL-2 (R IL-2) was added to PHA-induced PBMC cultures with high doses of GH, a reconstitution of lymphoproliferation was observed. Further experiments seem to exclude the presence of suppressor T lymphocyte induction by GH. The present results suggest that hypothesis that high concentrations of GH may interfere with the binding between IL-2 and its membrane receptor on activated lymphocytes.

Adult↗

[Hyperthyroidism in children (author's transl)].

The present paper analyzes the causes, signs and symptoms of hyperthyroidism in children and the problems, complications and results associated with the various therapeutic regimes. Childhood hyperthyroidism is usually due to Grave's disease, an autoimmune thyroid disease. Genetic factors are also involved in its development. The diagnosis and in particular the differential diagnosis with Hashimoto's thyroiditis are discussed. Treatment of Graves' disease is controversial, but medical therapy is commonly accepted as the treatment of choice. Some dosage schedules of antithyroid drugs are considered, and some techniques for predicting remission status and relapse of disease are reported. Both the minor and more serious complications of medical therapy are examined. Careful follow-up for the development of hypothyroidism is advocated, especially in patients treated with radiation or surgery. Autonomous hyperfunctioning thyroid adenoma is rare, but occurs even in childhood, and can degenerate into carcinoma.

Adolescent↗

[Buschke's scleredema and carditis: a clinical case].

An 11-year old girl who presented non-pitting edema of the face and neck, shoulder pain and a gallop rhythm about 10 days after a febrile episode with sore throat is described. The mask-like facial appearance and limited movement of the neck led to suspect scleredema which may be accompanied by carditis. Skin and muscle biopsy findings confirmed the diagnosis. Cardiac involvement included a gallop rhythm persisting for 6 months, ECG changes consisting in transitory T-wave inversion in leads II and V2 - V4, a transitory pericardial function rub and hepatomegaly due to right-sided failure which responded to digitalization. In this case the presence of a gallop rhythm and elevated ASLO titer led to an initial diagnosis of acute rheumatic fever; dermatomysitis and sclerodermia are also to be considered in the differential diagnosis of scleredema of Buschke. In our patient the edema resolved completely within 12 months, the gallop rhythm within 6 months and the ECG became normal after 8 months.

Arrhythmias, Cardiac↗

Late effects in children after bone marrow transplantation: a review.

Since the number of children receiving a bone marrow transplantation (BMT) and becoming long-term survivors continues to increase, more attention has to be paid to detect long-term side effects in these unique patients. Follow-up studies to timely identify these untoward sequelae are a matter of particular concern for pediatricians due to the longer life expectancy of children cured by BMT. The more frequently recognized sequelae affecting lung, eyes, brain and the endocrine system have been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare children before marrow transplantation and radiotherapy has been indicated as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this growth impairment is especially observed in patients receiving total body irradiation (TBI) and prophylactic cranial irradiation prior to marrow transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impairment of liver somatomedin production or a direct radiation-induced skeletal dysplasia could not be excluded. Overt and compensated hypothyroidism have been reported after TBI and patients given single dose radiotherapy are at greater risk with an overall incidence of thyroid function abnormalities approaching 30-40%. Delayed puberty development was reported in boys and girls after a TBI-containing conditioning regimen, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to the growth impairment of prepubertal children. In post-pubertal patients amenorrhea, azoospermia and gonadal failure can be observed after radiotherapy and several patients can require hormonal substitutive therapy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abnormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recognized complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more frequently in patients given TB1 as single exposure. Decreased lacrimal gland function, with impairment of tear production is another late effect of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow Transplantation↗