Biomedical subjects

M Cisternino

Publications and source records attributed to M Cisternino.

At least 37 records · Page 2Linked to original sources

PubMed1998

Hormonal replacement therapy with HCG and HU-FSH in thalassaemic patients affected by hypogonadotropic hypogonadism.

Gonadotropin (Gn) replacement therapy using HCG plus HU-FSH was administered to 24 patients affected by beta-thalassaemia major with hypogonadotropic hypogonadism aged 18-40 years (25.2 +/- 5.4 yr, m +/- SEM). The age range at the start of treatment was 14.5-24.5 years (16.7 +/- 2.6 yr); the mean duration of Gn treatment was 8.6 +/- 3.9 years (range 1-15.2 yr). Gn therapy was begun with HCG alone, the dosage being initially 500 IU twice a week and then increased to a maximum of 3000 IU twice a week, according to the individual serum testosterone levels obtained. HU-FSH (75 IU twice a week) was added to initiate spermatogenesis in all cases when the HCG-induced testosterone serum levels normalized. The duration of HU-FSH treatment ranged from 1-2 years and then therapy was continued with HCG alone. In nine patients Gn therapy was discontinued after 6-14 years and was replaced by testosterone depot therapy, 75-100 mg i.m. twice a month, for a period ranging from 1-1.5 years. Using Gn therapy, the testosterone levels normalized. The compliant patients obtained good virilization and normal sexual function; testicular volume increased within the normal adult range and spermatogenesis was achieved. When Gn therapy was replaced by testosterone-depot therapy, a marked decrease in testicular volume and sperm count was observed, but the patients complied better and showed a slight increase in coarse hair. In conclusion gonadotropins are an effective replacement therapy for male hypogonadism in thalassaemic patients. If we consider the advantages and disadvantages of this therapy, the former seem to outweigh the latter. Finally, it should be emphasized that physicians caring for these patients must foster compliance during frequent check-ups and examinations.

Adolescent↗

PubMed1996

Role of magnetic resonance imaging in the diagnosis and prognosis of growth hormone deficiency.

OBJECTIVE: In patients with congenital GH deficiency (GHD), magnetic resonance imaging (MRI) has revealed morphological abnormalities such as pituitary hypoplasia, absence of the stalk and ectopia of the posterior pituitary (PPE). Our study was aimed at investigating the possible relationship between neuroradiological images and the presence of isolated GH or multiple pituitary hormone deficiency. DESIGN: We studied 121 patients, aged 0.3-25 years, with isolated GHD (IGHD, 81 cases) or multiple pituitary hormone deficiency (MPHD, 40 cases). Of 81 IGHD patients, 50 were at prepubertal and 22 at pubertal age, while 9 had a delayed onset of puberty. Out of 40 MPHD patients, 25 were at prepubertal age and 15 at the age of puberty. RESULTS: Pituitary hypoplasia, defined as a gland with a height of less than -2 SD for age, was observed more frequently in prepubertal (66%) than pubertal (18%) IGHD patients. It was also found in the majority of MPHD patients of prepubertal (76%) and pubertal age (80%), and of IGHD patients with delayed onset of puberty (100%). Mean +/- SEM pituitary height was significantly lower (P < 0.001) in both prepubertal IGHD (-2.70 +/- 0.20 SD) and MPHD children (-3.10 +/- 0.39 SD) than in IGHD patients with normal onset of puberty (-1.55 +/- 0.2 SD). A significantly greater pituitary height was observed in IGHD patients with normal onset of puberty (-1.55 +/- 0.20 SD) than in MPHD patients at the age of puberty (-4.38 +/- 0.61 SD, P < 0.001) and in IGHD subjects with delayed onset of puberty (-4.06 +/- 0.41 SD, P < 0.001). An important increase (P < 0.02) in the height of the pituitary gland was found in 6 of the 9 patients with delayed puberty when they were re-evaluated after completing their spontaneous pubertal development. The frequency of other MRI abnormalities (PPE, stalk transection) was significantly higher in MPHD patients than in IGHD patients (P < 0.001). CONCLUSION: Our results confirm the usefulness of MRI in the evaluation of children affected by GH deficiency. The association of gland hypoplasia with other MR abnormalities could suggest the presence of multiple anterior pituitary deficiencies. Finally, puberty seems to play an important role in the increase of pituitary size in multiple pituitary hormone deficiency and isolated GH deficiency patients.

Adolescent↗

PubMed1995

Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone.

Seventy-six prepubertal children receiving autologous or allogeneic bone marrow transplantation (BMT) were enrolled in a prospective study on the impact of different pretransplant preparative regimens on growth. Patients were divided into three groups: group I, consisting of 37 children who had received total body irradiation (TBI) and cytotoxic drugs as preparative regimen; group II, including 17 children receiving prophylactic cranial irradiation before being conditioned with TBI and cytotoxic drugs; and group III, composed of 22 patients transplanted after a busulfan (BU)-containing myeloablative therapy. All patients have a minimum follow-up of 2 years, whereas 48 and 34 patients have been studied until 3 and 4 years after transplant, respectively. Height and growth rate were expressed as standard deviation score (SDS). Growth hormone (GH) secretion in response to pharmacologic stimuli was evaluated after documented growth failure. Patients with GH deficiency were treated with recombinant human GH, and response to therapy was evaluated. The main impairment of growth rate in patients belonging to group II was observed in the first year after TBI (growth rate SDS changing from -0.12 +/- 0.23 to -1.23 +/- 0.25, P < .005), with only a slight loss in the following years, whereas in group I children growth failure occurred in the third year after TBI (-1.36 +/- 0.28 SDS in comparison to a pre-BMT SDS of 0.10 +/- 0.15, P < .005). Therefore, growth velocity between these two groups differed significantly in the first 2 years (P < .01) but subsequently equalized. On the contrary, all BU-treated children but 2 grew normally. GH deficiency was shown in the vast majority of children with growth impairment. Twenty-three children treated with recombinant human GH are evaluable; a successful response was observed in all but 1, with the mean growth rate increasing from -2.29 +/- 0.27 before treatment to 0.86 +/- 0.38 and to 1.66 +/- 0.56 SDS at 1 and 2 years after treatment, respectively (P < .001). In conclusion, growth rate impairment was common in patients receiving TBI, with the speed of onset of both decreased growth velocity and GH deficiency depending mainly on the total dose of radiation. On the contrary, patients receiving BU did not experience significant problems in terms of growth velocity. The timely start of appropriate hormonal replacement therapy may ameliorate the final growth of children undergoing BMT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Auxological, clinical and neuroradiological findings in infants with early onset growth hormone deficiency.

Sixteen infants less than 2 years of age with apparently idiopathic hypopituitarism were studied. At birth, 11 of 16 patients (69%) had subnormal length associated with relative adiposity and 10 of 16 (62%) showed significant deterioration in length deficiency from birth onwards. These findings suggest that: (a) growth hormone deficiency, in a number of patients, had started well before delivery; (b) growth hormones may play a role in intrauterine growth; and (c) growth hormone may also be involved in early postnatal growth. Magnetic resonance imaging in these patients was very similar to that described in hypopituitarism of later onset. This suggests that even in the latter case, hypopituitarism may have a prenatal onset. Finally, the severity of growth failure and the coexistence of other hypopituitary symptoms at the time of diagnosis in 31% of our patients indicate that early clinical screening of hypopituitarism is possible.

Adrenal Cortex Function Tests↗

PubMed1995

Use of combined Gn-RH agonist and hGH therapy for better attining the goals in precocious puberty treatment.

We studied 30 girls (age 6.36 +/- 1.21 years, range 4.6-8.8) affected by idiopathic precocious puberty with significant reduction of height velocity (below the 25th centile) at the end of 1 year of Gn-RHa (triptorelin intramuscular depot) treatment, to evaluate GH-IGF-I axis activity and the effects of combined Gn-RHa plus hGH therapy. After 12 months, 15 patients continued Gn-RHa and started hGH therapy for 12 months, while 15 continued treatment with Gn-RHa alone (control group). We evaluated height velocity, bone age, urinary GH, serum IGF-I and IGFBP-3 levels throughout the study; plasma GHBP levels were determined only in the first 12 months of Gn-RHa treatment. Height velocity decreased significantly during Gn-RHa treatment; it increased significantly and became higher than the control group after 12 months of Gn-RHa plus hGH treatment. During Gn-RHa therapy alone, bone age progressed less than chronological age, while in the 12 months of Gn-RHa plus hGH treatment there was a slight nonsignificant increase in bone age progression in comparison to controls. Serum IGF-I and IGFBP-3 levels decreased significantly at 12 months of Gn-RHa therapy and increased significantly after Gn-RHa plus hGH treatment. Urinary GH levels showed the same behavior. Plasma GH binding to peak II-BP, slightly lower than the prepubertal normal range before treatment, significantly increased after 12 months of Gn-RHa treatment. Therefore, in these girls, during Gn-RHa treatment alone, we have a reduction in GH-IGF-I axis activity. During Gn-RHa plus hGH therapy there was a significant increase in height velocity, in urinary GH levels, in serum IGF-I and IGFBP-3 levels. Bone age did not seem to advance faster than chronological age and this may imply a better prediction in adult height. In our opinion, only in a small percentage of patients affected by precocious puberty (with a very low predicted adult height or an important reduction of growth velocity during Gn-RHa treatment) may an association with hGH therapy be useful.

Body Height↗

PubMed1995

Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers.

Two novel mutations in the sex-determining gene SRY were identified by screening DNA from 30 sex-reversed XY females by using the SSCP assay. Both point mutations lead to an amino acid substitution in the DNA-binding high-mobility-group domain of the SRY protein. The first mutation, changing a serine at position 91 to glycine, was found in a sporadic case. The second mutation, leading to replacement of a highly conserved proline at position 125 with leucine, is shared by three members of the same family, two sisters and a half sister having the same father. The mutant SRY proteins showed reduced DNA-binding ability in a gel-shift assay. Analysis of lymphocyte DNA from the respective fathers revealed that they carry both the wild-type and the mutant version of the SRY gene. The fact that both fathers transmitted the mutant SRY copy to their offspring implies that they are mosaic for the SRY gene in testis as well as in blood, as a result of a mutation during early embryonic development.

Adolescent↗

PubMed1994

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone-releasing hormone agonist treatments.

In order to evaluate the effects of two long-acting luteinizing hormone-releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 +/- 0.9 years, bone age (BA) was 10.2 +/- 1.1 years and height was 131.9 +/- 5.0 cm. Patients in group B started therapy when CA was 7.6 +/- 0.5 years, BA 9.8 +/- 1.0 years and height 133.2 +/- 7.6 cm. The diagnosis of untreated patients (group C) was made when CA was 7.2 +/- 0.9 years, BA 9.6 +/- 2.2 years and height 130.2 +/- 8.6 cm. Both luteinizing hormone-releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 +/- 5.7 cm) was significantly higher than that of group A (153.2 +/- 5.0 cm: p < 0.05) and group C (149.6 +/- 6.3; p < 0.01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 +/- 5.7 cm) and target height (157.6 +/- 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 +/- 5.3 and 156.4 +/- 1.3 cm, respectively), but only in group C the difference was statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1993

Functional disomy of Xp22-pter in three males carrying a portion of Xp translocated to Yq.

A number of Xp22;Yq11 translocations involving the transposition of Yq material to the distal short arm of the X chromosome have been described. The reciprocal product, i.e. the derivative Y chromosome resulting from the translocation of a portion of Xp to Yq, has never been recovered. We searched for this reciprocal product by performing dosage analysis of Xp22-pter loci in 9 individuals carrying a non-fluorescent Y chromosome. In three mentally retarded and dysmorphic patients, dosage analysis indicated the duplication of Xp22 loci. Use of the highly polymorphic probe CRI-S232 demonstrated the inheritance of paternal Xp-specific alleles in the probands. In situ hybridization, performed in one case, confirmed that 29CL pseudoautosomal sequences were present, in addition to Xpter and Ypter, in the telomeric portion of Yq. To our knowledge, these are the first cases in which the translocation of Xp material to Yq has been demonstrated. The X and Y breakpoints were mapped in the three patients by dosage and deletion analysis. The X breakpoint falls, in the three cases, in a region of Xp22 that is not recognized as sharing sequence similarities with the Y chromosome, thus suggesting that these translocations are not the result of a homologous recombination event.

Adolescent↗

PubMed1993

Growth in children after bone marrow transplantation.

Growth velocity pattern and growth hormone (GH) secretion were evaluated in 18 prepubertal patients (13 males, 5 females), receiving an allogeneic (7 patients) or autologous (11 patients) bone marrow transplantation (BMT). Children were affected by oncological or hematological malignancies and the age range was between 2 and 11 years. Nine patients received a conditioning regimen consisting of chemotherapy and fractionated total body irradiation (TBI) (12 Gy in 6 fractions over 3 days), whereas 9 children also received previous prophylactic cranial irradiation during first-line chemotherapy. GH secretion in response to pharmacological stimuli (insulin, arginine and/or L-Dopa) was evaluated when growth failure occurred. The 9 prepubertal patients who had received previous prophylactic cranial irradiation during first-line chemotherapy, showed a significant decrease in growth rate already 1 year after BMT and this reduced growth rate presented a progressive further decrease in the 2nd and 3rd year after BMT. On the contrary, in the 9 prepubertal children treated with TBI and chemotherapy alone, growth rate presented an impressive decrease only during the 3rd year. In the two groups of patients, pretransplantation growth rates were comparable, while, due to the earlier growth failure in children receiving TBI and previous prophylactic cranial irradiation, mean standard deviation score (SDS) significantly differed at 1 and 2 years following BMT. Such a difference disappeared at 3 years after BMT, because of the late decrease in growth rate in patients given TBI and chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗

PubMed1992

Final height attainment and gonadal function in girls with precocious puberty treated with cyproterone acetate.

Thirty-four girls with precocious puberty (27 idiopathic, 6 cerebral, 1 McCune-Albright syndrome) were treated with cyproterone acetate (CPA) for 1.2-8.4 years (3.71 +/- 0.31; mean +/- SEM) at a daily dosage of 66-150 mg/m2 (103.7 +/- 6.2). The mean chronological age (CA) and bone age at the beginning of treatment were 5.99 +/- 0.31 and 8.6 +/- 0.39 years, respectively, and 9.78 +/- 0.19 and 12.44 +/- 0.22 years, respectively, at the end of therapy. At the last evaluation, mean CA was 14.23 +/- 0.4 years, and 32 girls had reached final height. The control group consisted of 10 girls with idiopathic precocious puberty who, at their parents' request, were not treated. Mean CA at the onset of pubertal signs was 6.05 +/- 0.25 years. All patients had reached final height at the time of the last observation. There was no significant difference between final height of treated (152.43 +/- 1.36 cm) and untreated (149.55 +/- 1.99 cm) girls. Final height was significantly lower than target height in both treated (155.08 +/- 0.92 cm; p < 0.025) and untreated (156.45 +/- 1.29 cm; p < 0.0005) patients, but the mean height of treated patients is nearer to target height than that of untreated ones. A positive correlation was found between final height and target height both in treated (p < 0.005) and untreated (p < 0.05) patients. After the discontinuation of CPA treatment all girls resumed the progressive course of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

PubMed1991

Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism.

Fifteen patients aged 14.5-27.3 years (mean +/- SE 18.8 +/- 0.9) with pubertal development failure underwent replacement therapy with estradiol (E2) using a transdermal therapeutic system (TTS). Fourteen of them were affected by hypogonadotropic hypogonadism (11 with thalassemia major, 3 with multiple pituitary hormone deficiency), the 15th patient had an asymmetric gonadal dysgenesis (karyotype 45, X 0/46, XY). Two sizes (5 and 10 cm2) of E2 TTS, delivering respectively 25 and 50 micrograms of E2 a day for 3 1/2 days, were used in this study. All patients were initially given the lower dose of 25 micrograms, twice weekly for 3 weeks each month; 6 months after starting therapy, 5-10 mg oral medroxyprogesterone acetate (MPA) daily was added during the third week. Later, the following sequence was used: 25 micrograms E2 TTS (twice weekly), on days 1 through 14, and 50 micrograms E2 TTS (twice weekly), on days 15 through 25 of each month. On days 15 through 25, 5 mg daily of MPA were administered orally. The period of treatment ranged from 0.5 to 3 years. Breast development was obtained in all cases. The vaginal maturation index rose. Ultrasonography showed an increase of uterine size and uterine shape became of pubertal type. Withdrawal bleeding occurred in all patients. Plasma E2 levels rose to normal levels, estrone (E1) levels increased slightly. No change in plasma SHBG levels was observed. Urinary E2, E1 and estriol rose to maximum levels the 3rd day after the application of each system. Neither systemic side effects nor adverse metabolic effects were observed except for an increased sensitivity to the platelet aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed1991

Growth hormone response following growth hormone releasing hormone injection in thalassemia major: influence of pubertal development.

Thirty-five patients with thalassemia major, aged 7 to 21 years, were studied to define the relationship between the pubertal development and the growth-hormone (GH) secretion during sleep, after administration of GH-releasing factor (hpGRF 1-44), and betaxolol-glucagon or arginin-insulin. Pubertal development was classified as being appropriate or delayed for chronological age. GH response to pharmacological stimuli and during sleep was not linked to the pubertal development according to the chronological age. The peak of GH secretion after GHRH injection was significantly delayed in thalassemic patients with retarded puberty. The integrated secretion of GH during the 120-min test was slightly but not significantly reduced in these patients. The prepubertal pattern of GHRH response was restored in the patients receiving substitutive therapy by HCG or testosterone. The alteration of GH response to GHRH in thalassemic patients is likely to be only due to delayed puberty and decreased endogeneous GHRH secretion since it is corrected by androgen or gonadotropin replacement.

Adolescent↗

PubMed1991

Effect of corticoid therapy on growth hormone secretion.

Exogenous corticoids are known to be potent inhibitors of linear growth in children. We investigated the mechanisms underlying growth failure by evaluating growth hormone (GH) release during short-term high-dose prednisone treatment (40 mg/m2/day given orally in 3 divided doses) and 7 days after steroid withdrawal in 7 prepubertal children (4 males, 3 females, age range 3-12 years), affected by acute lymphoblastic leukemia. Patients also received weekly administrations of vincristine (1.5 mg/m2 i.v.), daunomycin (20 mg/m2 i.v.) and L-asparaginase (6,000 IU/m2 i.m.). Corticoid therapy suppressed GH secretion during deep sleep as well as in response to arginine, insulin and GH-releasing hormone (GHRH) administration. A significant recovery of GH responsiveness after drug discontinuation was observed during deep sleep (14.03 +/- 3.47 vs. 1.49 +/- 0.43 ng/ml, p less than 0.025) as well as in response to arginine (13.63 +/- 2.73 vs. 4.95 +/- 1.54 ng/ml, p less than 0.025) and GHRH (32.62 +/- 4.59 vs. 7.27 +/- 3.52 ng/ml, p less than 0.005) but not to insulin (7.12 +/- 0.88 vs. 4.47 +/- 0.96 ng/ml, p = NS). Insulin-like growth factor 1 levels during deep sleep (0.61 +/- 0.13 IU/ml/min) were found to be low in the course of steroid therapy and did not increase after drug withdrawal (0.41 +/- 0.07 IU/ml/min). Our preliminary data suggest that recovery of adrenergic response to insulin does not immediately follow corticosteroid discontinuation.

Arginine↗

PubMed1991

Modifications of the nasal cycle in patients with hypothalamic disorders: Kallmann's syndrome.

The nasal cycle is a phenomenon characterized by cyclic changes in the airflow resistance of each nasal fossa from congestion or constriction of the nasal erectile tissue. This phenomenon is caused by alterations in the influence exerted by the autonomic nervous system and is believed to be regulated by a hypothalamic center. In order to verify this hypothesis on the hypothalamic regulation of the nasal cycle, the authors studied a group of subjects with Kallmann's syndrome. This disorder is characterized by coexisting hypothalamic hypogonadism and hyposmia or anosmia due to hypothalamic and olfactory center hypoplasia. An anomalous nasal cycle was found in all the subjects with Kallmann's syndrome. This disorder might be related to hypothalamus atrophy.

Adolescent↗

PubMed1991