Biomedical subjects

G Saggese

Publications and source records attributed to G Saggese.

At least 91 records · Page 5Linked to original sources

PubMed1993

Ketoconazole decreases the serum ionized calcium and 1,25-dihydroxyvitamin D levels in tuberculosis-associated hypercalcemia.

OBJECTIVE: To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. DESIGN: Case study. SETTING: Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). PARTICIPANTS: Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. MEASUREMENTS/MAIN RESULTS: At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [-13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other). CONCLUSIONS: Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.

25-Hydroxyvitamin D 2↗

PubMed1993

Reduction of bone density: an effect of gonadotropin releasing hormone analogue treatment in central precocious puberty.

Gonadal steroids drive the significant bone mineral increase that occurs at puberty. Oestrogen deprivation in women results in bone loss. We investigated bone mineralization by single photon absorptiometry in girls with central precocious puberty (n = 13, age 3.8-8.5 years) before and during 1 year of treatment with gonadotropin releasing hormone analogue (GnRH-a = long-acting D-Trp6-GnRH, 60 micrograms i.m. every 28 days). Before GnRH-a therapy, bone mineral density (BMD) was significantly higher in patients than in ten control girls matched for chronological age (patients 0.575 +/- 0.097 g/cm2, controls 0.433 +/- 0.049 g/cm2, P < 0.001). Patient BMD was not significantly different from that of ten control girls matched according to patient bone, age (0.550 +/- 0.046 g/cm2, P = NS). During GnRH-a treatment, pituitary-gonadal axis was suppressed and patient BMD significantly decreased (6 months: -6.0%, P < 0.002 vs baseline; 12 months: -8.0%, P < 0.001 vs baseline). We conclude that in girls with precocious puberty the activation of gonadal steroid secretion induces an increase in bone mineralization and that oestrogen deprivation by GnRH-a treatment caused a significant decrease in BMD.

Absorptiometry, Photon↗

PubMed1993

Topical application of 1,25-dihydroxyvitamin D3 (calcitriol) is an effective and reliable therapy to cure skin lesions in psoriatic children.

We studied, in vivo, the effects of a calcitriol-containing ointment (3 micrograms of calcitriol per gram of petrolatum) topically applied on skin lesions in children affected by psoriasis vulgaris. Each patient was instructed to apply the ointment, about 1 g once a day at bedtime followed by occlusive dressing with plastic wrap, on one-side lesion (treated) and petrolatum alone on the equivalent controlateral site (placebo) (total weekly dose of calcitriol: approximately 21 micrograms/patient). After 4 weeks of topical treatment all children showed a complete clearing of their skin lesions on the treated side, without appreciable changes on the placebo side. Serum ionised calcium, calcium and calcitriol levels or urinary calcium excretion did not vary significantly throughout the period of therapy. These findings suggest that topical calcitriol may be an effective and safe alternative therapy for psoriasis in children.

Administration, Cutaneous↗

PubMed1993

Effects of long-term treatment with growth hormone on bone and mineral metabolism in children with growth hormone deficiency.

The effects of growth hormone (GH) deficiency and recombinant human GH replacement (0.6 IU/kg per week) on bone and mineral metabolism in 26 GH-deficient children were studied for 12 months. Before therapy, all children had significantly reduced serum levels of osteocalcin, carboxyl-terminal propeptide of procollagen type I, and 1,25-dihydroxyvitamin D, whereas serum ionized calcium, phosphate, intact parathyroid hormone, calcitonin, and 25-hydroxyvitamin D concentrations were in the normal range. All children had significant reduction of bone density for their chronologic, statural, and bone ages. During therapy with recombinant human GH, a decrease of serum ionized calcium levels and increases of phosphate, osteocalcin, carboxyl-terminal propeptide of procollagen type I, and intact serum levels of parathyroid hormone were found. A significant increase of serum levels of 1,25-dihydroxyvitamin D was found at 12 months. The urinary phosphate/urinary creatinine ratio decreased, whereas values for nephrogenous cyclic adenosine monophosphate and the ratio of the maximum rate of renal tubular reabsorption of phosphate to the glomerular filtration rate increased. Bone density significantly improved at 12 months, with a complete recovery in 12 children (46.2%). Significant relationships were found among growth velocity, bone density, maximum tubular reabsorption/glomerular filtration rate ratio, and serum levels of carboxyl-terminal propeptide of type I procollagen. The changes in serum levels of this propeptide during the first week of recombinant human GH treatment were positively related to growth velocity at 6 and 12 months and to bone density at 12 months of treatment, whereas the changes in osteocalcin levels were not. We conclude that recombinant human GH treatment caused significant modifications of mineral metabolism and significantly increased bone density, and that measurement of serum levels of the propeptide during the first week of recombinant human GH administration may be a useful tool in predicting improved growth velocity and bone density during long-term recombinant human GH replacement.

Bone Density↗

PubMed1993

Growth velocity and serum aminoterminal propeptide of type III procollagen in precocious puberty during gonadotropin-releasing hormone analogue treatment.

Growth velocity and serum aminoterminal propeptide of type III procollagen (P-III-NP) were evaluated in 11 girls (age 3.8-8.5 years) with central precocious puberty during luteinizing hormone releasing hormone (LH-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im for 28 days, n = 7; D-ser(TBU)6-LH-RH, 1600 micrograms/day intranasally, n = 4). Before treatment, growth velocity (10.2 +/- 1.9 cm/year) and P-III-NP concentrations (12.8 +/- 4.3 micrograms/l) were in the pubertal range. During therapy, growth velocity significantly decreased to the prepubertal levels. P-III-NP concentrations decreased significantly after six months of therapy (7.9 +/- 3.7 micrograms/l, p < 0.001). Three girls with low growth velocity ( < 4 cm/year), stimulated growth hormone peak < 10 micrograms/l, and altered 12-h nocturnal growth hormone secretion at 12 and/or 18 months of treatment, had a more marked decrease in P-III-NP concentrations (patient 3: -65.9%; patient 5: -58.7%; patient 10: -61.0%) after 6 months of therapy. Our results suggest that LH-RH analogue treatment in central precocious puberty may impair growth. In these cases, measurement of serum P-III-NP levels may be an additional marker to monitor growth.

Child↗

PubMed1993

In vitro effects of growth hormone and other hormones on chondrocytes and osteoblast-like cells.

The influence of growth hormone (GH), insulin-like growth factor I (IGF-I), parathyroid hormone(1-34) (PTH(1-34)), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 17 beta-oestradiol on proliferation and on production of cytokines, such as interleukin-1 beta (IL-1 beta), IL-6, IL-8 and transforming growth factor-beta (TGF-beta), was studied in chondrocytes obtained from the growing cartilage of the iliac crest and in the osteoblast-like cell clone SaOS-2. GH and IGF-I were mitogenic for chondrocytes and SaOS-2 cells, as indicated by the dose-related increase in uptake of [3H]thymidine. PTH(1-34) was also mitogenic, while 1,25(OH)2D3 inhibited the proliferation of both chondrocytes and SaOS-2 cells in a dose-dependent manner. 17 beta-oestradiol was stimulatory in SaOS-2 cells, but gave a biphasic pattern in chondrocytes; it was stimulatory at low concentrations (0.1 nmol/l) and inhibitory at supraphysiological doses (10 nmol/l). Using the cDNA polymerase chain reaction, specific mRNAs for IL-1 beta, IL-6, IL-8 and TGF-beta were found in chondrocytes, while SaOS-2 cells had a positive signal only for TGF-beta. Specific enzyme immunoassays revealed detectable levels of IL-1 beta, IL-6 and IL-8 only in chondrocytes. IL-6 was increased by GH and IGF-I, and lowered by 1,25(OH)2D3 and supraphysiological doses of 17 beta-oestradiol, while PTH(1-34) had no effects. IL-8 was not influenced by GH or IGF-I, was slightly but not significantly increased by PTH(1-34) and was reduced by 1,25(OH)2D3 and 17 beta-oestradiol at supraphysiological doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

PubMed1993

[Discitis in children. Report of two cases].

Two cases of intervertebral disk infection in 2 3-year-old boys are presented. The study reported on the anamnesis, clinical, laboratory and instrumental findings as well as therapy in both cases. Diagnosis was suspected on the basis of pain, refusal to assume any position that flexes the spine and irritability. Low-grade fever, the moderate increment of inflammatory indexes and the characteristic changes seen in 1 case on Magnetic Resonance Imaging (MRI) only and in the other one on both Technetium 99m polyphosphate bone-scanning and MRI verified the clinical diagnosis. Furthermore the authors briefs discuss the differential diagnosis of disc-space inflammation and several acute and subacute diseases of infancy and childhood some of them not localized in the spine (myopathy, appendicitis, peritonitis, urinary infections) for which discitis may be often mistaken.

Anti-Bacterial Agents↗

PubMed1993

Commercial kits for 1,25-dihydroxyvitamin D compared with a liquid-chromatographic assay.

Three commercially available kits for 1,25-dihydroxyvitamin D [1,25(OH)2D] determination were compared with a liquid-chromatographic method. Serum samples were analyzed for 1,25(OH)2D from 70 healthy subjects (age 2.2-17.5 years; 35 males, 35 females), some (n = 5) given orally high vitamin D3 doses. In addition, 1,25(OH)2D was measured in 28 patients with untreated diseases associated with low (n = 16) or high (n = 12) serum concentrations of the hormone. The results showed that the commercial kits were sufficiently accurate with respect to the comparison method and suitable for routine clinical work.

Adolescent↗

PubMed1992

Idiopathic juvenile osteoporosis: evidence of normal osteoblast function by 1,25-dihydroxyvitamin D3 stimulation test.

Idiopathic juvenile osteoporosis (IJO) is a rare form of bone demineralization that occurs during childhood. The mechanism of bone loss is unclear. Some bone hystomorphometric studies have found osteoblast failure and decreased bone formation in the affected patients whereas others have reported increased bone resorption. To elucidate this issue, we studied osteoblast function in six patients with IJO (five males, one female; aged 2.3-14.6 years) and five healthy sex- and age-matched subjects (four males, one female; aged 2.0-15.1 years) measuring serum values of osteocalcin under basal condition and during an osteoblast stimulation test performed by oral 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] administration (1.8 micrograms/1.73 m2/daily). After a baseline day (day 0), all the subjects (patients and controls) received 1,25(OH)2D3 in four divided doses for 6 days (days 1-6). Fasting blood samples were obtained every morning (0800 h) for the determination of serum osteocalcin. Baseline osteocalcin levels were not significantly different between IJO and controls (13.58 +/- 6.05 ng/ml versus 16.04 +/- 5.09 ng/ml, respectively) even if two patients had low osteocalcin values. During 1,25(OH)2D3 administration, serum osteocalcin values significantly increased (P less than 0.001) from baseline in both children with IJO and controls, reaching peak values not significantly different in the two groups. Our results do not support the hypothesis that defective osteoblast function is the primary factor of bone demineralization in IJO.

Adolescent↗

PubMed1992

Serum levels of carboxyterminal propeptide of type I procollagen in healthy children from 1st year of life to adulthood and in metabolic bone diseases.

Type I collagen is the major component of bone matrix; circulating carboxyterminal propeptide of type I procollagen (P-I-CP) levels reflect type I collagen synthesis in tissues and may be an useful index to investigate bone metabolism. We measured P-I-CP by a new radioimmunoassay in 300 healthy children and adolescents and in 40 healthy adults to provide reference data for P-I-CP values. In addition, 79 patients with diagnosed disorders of phospho-calcium metabolism (rickets, vitamin D deficient and vitamin D resistant, hyperparathyroidism, hypo- and pseudo-hypoparathyroidism, osteopenia) were evaluated. In the healthy subjects, serum P-I-CP values were higher in children than in adults; variations of P-I-CP levels were observed according to age and sexual maturation: higher values were found in the first years of life and during pubertal development; pubertal increase reflects the different timing of pubertal development in the two sexes. P-I-CP levels were increased in primary hyperparathyroidism and reduced in diseases related to impaired secretion or action of parathyroid hormone. Higher P-I-CP levels were found in vitamin D deficient and vitamin D resistant rickets. P-I-CP was reduced in anorexia nervosa and during chronic glucocorticoid treatment while it was increased in thyrotoxic osteoporosis. In idiopathic juvenile osteoporosis, P-I-CP values ranged from reduced to increased values. We conclude that P-I-CP may represent an additional biochemical marker of bone metabolism. Since age-related variations are present, reference data for the various ages are need for clinical application of this assay.

Adolescent↗

PubMed1992

Elevated calcitonin gene-related peptide in polycythemic newborn infants.

In this study, calcitonin gene-related peptide levels were measured in cord and at 16-36 h of extrauterine life in 43 polycythemic newborns; 20 healthy term infants were also studied as controls. Calcitonin gene-related peptide values were significantly higher in polycythemic neonates in comparison with controls both at delivery and at 16-36 h after birth. Five polycythemic (11.6%) infants who develop hypocalcemia had greater elevated calcitonin gene-related peptide concentrations. Our data suggest that calcitonin gene-related peptide may be implicated in the circulatory adaptation to extrauterine life. In polycythemic neonates, calcitonin gene-related peptide is probably increased to compensate for blood hyperviscosity; in some cases, high calcitonin gene-related peptide concentrations may induce hypocalcemia.

Adaptation, Physiological↗

PubMed1992

Stimulated growth hormone (GH) secretion in children with delays in pubertal development before and after the onset of puberty: relationship with peripheral plasma GH-releasing hormone and somatostatin levels.

A reduced GH secretion has often been shown in prepubertal children with delays in pubertal development. In order to study the mechanism underlying this finding, we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH) before and after the onset of sexual development in a group of eight late maturing children (six boys, two girls), comparing the results with those obtained in two groups of five prepubertal and four pubertal short children with familial short stature. GH was measured by a two-site immunoradiometric assay. Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether extraction from plasma. Our data showed a significant increase (P less than 0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa administration in all groups. In pubertal children with delays in pubertal development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18 pg/mL, respectively) were significantly greater (P less than 0.001) than in the same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL, respectively), whereas SRIH peak values did not significantly change (41 +/- 6 vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in pubertal development showed GH and GHRH peak values lower (P less than 0.001) than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/- 13 pg/mL, respectively), whereas no statistical difference was present between the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the assumption that in late maturing subjects during prepubertal period the decreased GH secretion may be ascribed to a reduced GHRH secretion, reversible with the onset of puberty, without change in circulating SRIH levels.

Adolescent↗

PubMed1992

Mineral metabolism in Turner's syndrome: evidence for impaired renal vitamin D metabolism and normal osteoblast function.

We examined intact PTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] in both baseline and dynamic conditions (low calcium diet) in 14 patients with Turner's syndrome (mean age, 12.6 +/- 5.9 yr; range, 4.2-21.0 yr) and bone demineralization as well as in a control group of 15 healthy girls (mean age, 12.8 +/- 5.6 yr; range, 3.8-22.7 yr). In both groups we also measured osteocalcin serum levels in response to oral 1,25-(OH)2D3 administration (1.8 micrograms/m2/daily for 6 days) to assess osteoblast function. The low calcium diet decreased ionized calcium (Ca2+) levels and elevated PTH values to the same extent in both patients (Ca2+, -8.40 +/- 3.78%; intact PTH, +47.88 +/- 13.24%) and controls (Ca2+, -9.09 +/- 3.25%; intact PTH, +52.77 +/- 10.52%; P = NS vs. patients). While controls showed an increment in their serum 1,25-(OH)2D levels (+52.15 +/- 8.95%), patients did not (+10.93 +/- 4.71%; P = NS vs. baseline; P < 0.001 vs. controls). 1,25-(OH)2D3 administration caused a rise in the serum osteocalcin levels in a similar fashion in both groups (peak values: patients, +35.38 +/- 7.20%; controls, +34.09 +/- 7.98%; P = NS). We conclude that in patients with Turner's syndrome there is an altered renal vitamin D metabolism in response to physiological stimulus, while osteoblast function in response to 1,25-(OH)2D3 administration is not affected.

Adolescent↗

PubMed1992

Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency.

In subjects with an isolated GH deficiency the inhibition of puberty by GnRH-analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1-5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp-6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23 +/- 1.49 (mean +/- SD) to 4.12 +/- 0.67 cm/year; p < 0.02), whereas height SD scores for bone age increased (from -0.75 +/- 0.42 to -0.47 +/- 0.55; p < 0.02). During the year of combined therapy, bone age increased only 0.57 +/- 0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p < 0.02 and p < 0.001, respectively). Our preliminary data showed that the addition of GnRH-analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved.

Body Height↗

PubMed1992

[Vitamin D prophylaxis in childhood].

The past 10 years have seen a return of rickets. Clinical and/or biochemical signs of vitamin D deficiency are still found in some children and adolescents, mainly during the winter. Sunlight exposure is able to prevent vitamin D deficiency and rickets but the dramatic influence of changes in solar ultraviolet-B radiation on cutaneous vitamin D3 synthesis, related to latitude and season effects, suggest that a vitamin D supplementation may be advisable. Moreover, human milk and common foods contain low quantities of vitamin D. So, we recommend routinely 400 IU of supplementary vitamin D per day in all infants. The vitamin D requirements in low-birth-weight infants are higher than at term infants; it is recommended the use of 1000-1600 IU per day in the first months of life. Intermittent high-dose of vitamin D and vitamin D metabolites are not advisable for prophylaxis of rickets.

Animals↗

PubMed1992

[The effects of l-dopa administration on the prolactin levels in short-stature subjects].

In this study, on the basis of the inhibiting action of l-dopa administration on prolactin (PRL) secretion, we evaluated in a number of short children the levels of PRL during the provocative stimuli test with l-dopa in order to identify an index able to give reliability to the test and to investigate whether some differences may exist among the subjects showing a different response in growth hormone (GH) secretion to l-dopa. We examined 76 subjects (44 boys and 32 girls) with chronological age from 4.5-15.17 years. The subjects, on the basis of the GH peaks during two provocative stimuli tests [l-dopa and insulin-induced hypoglycemia (IIH)], were subdivided into 3 groups: group 1 (n = 24) with both deficient responses (peak less than 10 ng/ml); group 2 (n = 28) with discordant responses and further subdivided into group 2a (n = 14) with normal responses to IIH and 2b (n = 14) with a normal response to l-dopa; group 3 (n = 24) with both normal responses. PRL levels peaked between times -20' (58 cases) and +20' (2 cases) whereas nadir occurred between +80' (4 cases) and +120 (48 cases) without any significant difference (p = ns) among the groups. PRL levels significantly decreased in all groups, also in those with a deficient response to l-dopa (1 and 2a); furthermore no significant correlation between PRL and GH levels was demonstrated. In conclusion, this study showed the importance of PRL evaluation during l-dopa test in order to give reliability to the test and did not demonstrate any difference in PRL levels among the examined groups of short children.

Adolescent↗

PubMed1992

[Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus].

In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease.

Child↗

PubMed1991

Mineral metabolism and calcitriol therapy in idiopathic juvenile osteoporosis.

Idiopathic juvenile osteoporosis is a rare cause of osteoporosis during childhood. We examined four children (three boys and one girl, ranging in age from 2.3 to 12.6 years) with idiopathic juvenile osteoporosis. All of these patients had normal serum calcium, ionized calcium, phosphate, magnesium, 25-hydroxyvitamin D, intact parathyroid hormone, and total and extractable calcitonin levels. 1,25-Dihydroxyvitamin D values were low in three patients and slightly decreased in one. Three children were treated with calcitriol (1,25-dihydroxycholecalciferol) (0.50 micrograms/d in two and 0.25 microgram/d in the other). The fourth patient was not treated because of parental refusal. Therapy reduced the fracture rate. Follow-up at 6 and 12 months showed a significant increase in bone mineralization, which reached normal values in two children after 12 months of treatment. No side effects of calcitriol therapy were observed. The untreated patient did not show an improvement of bone mineralization in the same time.

Bone Density↗