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Biomedical subjects

E Ferrante

Publications and source records attributed to E Ferrante.

At least 19 recordsLinked to original sources
PubMed2006

Growth hormone replacement therapy in growth hormone deficient children and adults: Effects on hemochrome.

Several lines of evidence have suggested a role of the GH/IGF-I axis in the regulation of hemochrome. Many studies have been carried out in GH deficient children and adults about this topic, reporting predominantly a positive effect of recombinant human GH (rhGH) on red series, with no action on serum leucocytes and platelets counts. The aim of this study was to assess the impact of GH deficiency (GHD) and of rhGH replacement on blood cells count in 17 pre-pubertal children with idiopathic isolated GHD (11 males and 6 females, aged 9.1+/-0.8 yr) and in 18 patients with adult-onset GHD (12 males and 6 females, aged 47.9+/-3.0 yr). Evaluation of absolute and SD score (SDS) values of red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets and white blood cells was performed at baseline and after 12 months of rhGH treatment (0.045+/-0.001 mg/kg bw/day and 4.2+/-0.5 microg/kg bw/day for children and adults, respectively). At baseline, all patients showed low IGF-I levels. Effectiveness of rhGH therapy was documented by significant increase in height SDS, height velocity and serum IGF-I levels in children. In adults, adequacy of rhGH was demonstrated by significant increase in serum IGF-I and significant decrease in body fat. At baseline, about 25% of patients (4 of 17 children and 4 of 18 adults) showed normochromic normocytic anemia, while the other indices were normal. In 7 of the 8 anemic patients, normal levels of hemoglobin were restored on rhGH, while no change in all the other indices was observed. In conclusion, rhGH therapy at physiological doses has no effect on erythropoiesis in GHD children and adults with normal blood cells count, while in patients with normochromic normocytic anemia rhGH is able to restore normal hemoglobin levels.

Adolescent↗
PubMed2006

Evaluation of the components of the insulin-like growth factors system in GH-deficient adults: effects of twelve-month rhGH treatment.

The impact of GH deficiency and rhGH replacement therapy on IGF-I, IGFBP-3 and ALS levels has been widely studied. There is less information available on IGF-II levels, the component of the ternary complex poorly dependent on GH. We investigate the components of IGFs system in 36 GHD adults (28M, 8F, age 45 +/- 14 yrs) before and after 12 months of rhGH therapy (mean dose 0.3 +/- 0.1 mg/day). One-hundred healthy sex- and age-matched subjects were studied for comparison. At baseline, GHD patients showed IGF-I and IGF-II levels and IGFs to IGFBP-3 molar ratios that were lower than controls. During therapy, IGF-I levels increased (p < 0.01) to normal range. IGF-II levels, though higher than at baseline (p < 0.01), remained lower than in controls (p < 0.01). ALS and IGFBP-3 significantly increased (p < 0.001). These modifications resulted in normalization in IGF-I to IGFBP-3 ratio, while no change in IGF-II to IGFBP-3 ratio was observed. In conclusion, the increase of serum IGF-II levels during rhGH treatment in GHD patients probably reflects the increase in the other components of ternary complex (ALS and IGFBP-3). However, serum IGF-II levels as well as IGF-II to IGFBP-3 ratio, although increased, were definitely lower than in controls. This last result, given the increasing evidences of a direct implication of IGF-II in cancer, may further confirm the safety of rhGH replacement in adults with severe GHD as diagnosed by appropriate stimulation tests.

Adult↗
PubMed2006

Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2.

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160+/-20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172+/-25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.

Acromegaly↗
PubMed2005

Effect of cyclic adenosine 3',5'-monophosphate/protein kinase a pathway on markers of cell proliferation in nonfunctioning pituitary adenomas.

CONTEXT: Alterations in cAMP signaling have been identified as a cause of endocrine neoplasia. In particular, activating mutations of the G(s)alpha gene and protein kinase A (PKA) overactivity due to low expression of PKA regulatory subunit 1A (R1A) have been implicated in somatotroph proliferation. OBJECTIVE: The objective of this study was to evaluate the effects of cAMP-PKA cascade activation in nonfunctioning pituitary adenomas (NFPA). DESIGN AND METHODS: By immunohistochemistry, R1A, R2A, and R2B expression was evaluated in cells obtained from eight surgically removed NFPA positive for gonadotropins. Cyclin D1 expression and ERK1/2 activity were analyzed under basal conditions and after cAMP-PKA cascade activation. RESULTS: Immunohistochemistry studies demonstrated a low R1/R2 ratio in all NFPA. Additional unbalance of R1/R2 ratio by 8-chloroadenosine cAMP (8-Cl-cAMP) and direct adenylyl cyclase stimulation by forskolin did not increase cyclin D1 expression or ERK1/2 activity in five NFPA (group 1), but even caused 74 +/- 15% and 85 +/- 13% inhibitions of cyclin D1 and ERK1/2 activity, respectively, in the remaining NFPA (group 2). Moreover, in group 2, PKA blockade by the specific inhibitor PKI increased cyclin D1 expression (96 +/- 25% over basal) and ERK1/2 activity (116 +/- 28% over basal). CONCLUSIONS: These data show that in contrast with what was previously observed in transformed somatotrophs, activation of the cAMP-PKA pathway did not generate proliferative signals in tumoral cells of the gonadotroph lineage, and in a subset of tumors even exerted a tonic inhibitory effect, thus confirming a different role for the cAMP-mediated pathway in promoting proliferation in the pituitary.

Adenoma↗
PubMed2004

Gonadotropin-releasing hormone initiates multiple signaling pathways in human GH-secreting adenomas.

Abnormal GH responses to GnRH test, observed in about 15% of patients with acromegaly, have been reported exclusively in patients bearing tumors without gsp mutation. The absence of responsiveness to GnRH in gsp+ tumors was not predicted on the basis of the mechanism of GnRH action that mainly involves the activation of calcium and protein kinase C dependent pathways. The aim of the present study was to investigate in detail the transduction of GnRH signaling in these tumors. GH-secreting adenomas removed from patients in vivo responsive to GnRH test were studied. Tumor DNA was screened for Gsalpha and GnRH receptor gene sequences. Intracellular calcium ([Ca2+]i) and cAMP levels were measured in dispersed cells and adenylyl cyclase (AC) activity in membrane preparations. DNA analysis showed wild sequence of both Gsalpha and GnRH receptor genes. GnRH caused a significant increase in intracellular Ca2+ that was associated with a significant stimulation of cAMP accumulation. In these cells neither TRH nor GHRP-6 were effective in causing significant modifications of cAMP levels, despite their ability to increase [Ca2+]i. Finally, GnRH was able to directly stimulate AC from 11.1 +/- 3.3 pmol/mg prot/min to 26.9 +/- 5.4 (p<0.005). We report that GnRH was effective in increasing both [Ca2+]i and AC in GH-secreting adenomas removed from responsive patients. The ability of GnRH to signal through Gsalpha protein may account for the lack of GH responses to GnRH observed in acromegalic patients with tumors carrying gsp mutation.

Acromegaly↗
PubMed2003

Postural headache in a patient with Marfan's syndrome.

A 26-year-old man with Marfan's syndrome had postural headache. Brain MRI with gadolinium showed diffuse pachymeningeal enhancement. MRI myelography revealed bilateral multiple large meningeal diverticula at sacral nerve roots level. He was suspected to have spontaneous intracranial hypotension syndrome. Eight days later headache improved with bed rest and hydration. One month after the onset he was asymptomatic and 3 months later brain MRI showed no evidence of diffuse pachymeningeal enhancement. The 1-year follow-up revealed no neurological abnormalities. The intracranial hypotension syndrome likely resulted from a CSF leak from one of the meningeal diverticula. In conclusion patients with spinal meningeal diverticula (frequently seen in Marfan's syndrome) might be at increased risk of developing CSF leaks, possibly secondary to Valsalva maneuver or minor unrecognized trauma.

Adult↗
PubMed2000

Current practice in assessment and treatment of bronchial asthma in young males in Italy.

The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti-inflammatory drugs were still underutilized.

Adult↗
PubMed1999

[Nutritional status, obesity and metabolic control in children with type 1 diabetes mellitus].

BACKGROUND AND AIMS: The aim of this study was to evaluate the nutritional status of children with type 1 diabetes and to search for possible influences of changes in body composition on aspects of diabetes. METHODS: A group of 96 diabetic subjects (41 males and 55 females) were studied, aged between 3 and 19 years old. The following parameters were examined: weight, stature, 5 skin folds, 7 circumferences, bioelectric impedance, arterial pressure, cholesterolemia, triglyceridemia, insulin dose, HbA1c and duration of disease. RESULTS: Obesity and overweight were present in 34.5% of the sample, but obesity was only observed in females (25.5%). There was also a high percentage of underweight subjects (11.5% of the entire sample). The mean values of weight BMI, 5 skin folds, 4 circumferences, FM (calculated using fold measurement and BIA) and AFA were higher in females, whereas mean values of waist/hip ratio and waist/thigh ratio and FFM (in % of body weight) were higher in males. A close correlation was also found between the 4 weight classes (underweight, normal weight, overweight, obese) and the majority of marker parameters for adiposity (5 folds, 4 circumferences, BIA, FM calculated using BIA, fold measurement and AFA). Of the other parameters examined (mean duration of disease, HbA1c assay, daily insulin dose, total cholesterolemia, triglycerididemia, arterial pressure), only the daily insulin dose showed higher values in females in 3 weight classes (underweight, normal weight and obese). Following a comparison with the control population (2469 subjects), higher mean values were found in the latter compared to diabetic subjects, but only in relation to 3 skin folds (tricipital, subscapular and suprailiac) and one circumference (forearm). CONCLUSIONS: The study shows a high frequency of overweight and obesity in children with type 1 diabetes, comparable to that in the healthy population. The finding of a higher frequency of obesity in diabetic females might be explained by their advanced puberal status, given that almost all the obese diabetic females were aged between 10 and 19 years old. The study confirms the validity of a number of anthropometric measurements (BMI, folds, circumference) and BIA in the evaluation of nutritional status in terms of body composition.

Adolescent↗
PubMed1999

Hypoxemia in young asthmatics with mild airway obstruction by methacholine challenge.

We studied 12 asymptomatic conscripts affected by bronchial asthma to evaluate the level of hypoxemia and its relationship with bronchial obstruction induced by methacholine (Mch) challenge. Arterial blood samples were obtained before and immediately after bronchial challenge. The range of decrease of forced expiratory volume/forced vital capacity x 100 in 1 second of expiration (FEV1), the absolute value reported as a percentage of the baseline value, after Mch challenge was from 21% to 36%. The mean decrease of arterial oxygen tension was 27 mm Hg (from 11.4 to 39.8 mm Hg), the mean decrease of hemoglobin saturation was 3.53% (from 0.4 to 7.2), and the mean increase of alveolar-arterial gradient for oxygen was 28.2 mm Hg. We found a significant correlation between the prechallenge and postchallenge differences of arterial oxygen tension and FEV1 (DFEV1P), which was expressed as a percentage of the predicted value. In conclusion, the Mch challenge seems to be a safe test, and the decrease of arterial oxygen tension can be sufficiently predicted by DFEV1P.

Adult↗
PubMed1999

[Nutritional status, obesity, and metabolic balance in pediatric patients with type I diabetes mellitus].

BACKGROUND AND AIMS: The aim of this study was to evaluate the nutritional status of children with type 1 diabetes and to search for possible influences of changes in body composition on aspects of diabetes. METHODS: A group of 96 diabetic subjects (41 males and 55 females) were studied, aged between 3 and 19 years old. The following parameters were examined: weight, stature, 5 skin folds, 7 circumferences, bioelectric impedance, arterial pressure, cholesterolemia, triglyceridemia, insulin dose, HbA1c and duration of disease. RESULTS: Obesity and overweight were present in 34.5% of the sample, but obesity was only observed in females (25.5%). There was also a high percentage of underweight subjects (11.5% of the entire sample). The mean values of weight BMI, 5 skin folds, 4 circumferences, FM (calculated using fold measurement and BIA) and AFA were higher in females, whereas mean values of waist/hip ratio and waist/thigh ratio and FFM (in % of body weight) were higher in males. A close correlation was also found between the 4 weight classes (underweight, normal weight, overweight, obese) and the majority of marker parameters for adiposity (5 folds, 4 circumferences, BIA, FM calculated using BIA, fold measurement and AFA). Of the other parameters examined (mean duration of disease, HbA1c assay, daily insulin dose, total cholesterolemia, triglycerididemia, arterial pressure), only the daily insulin dose showed higher values in females in 3 weight classes (underweight, normal weight and obese). Following a comparison with the control population (2469 subjects), higher mean values were found in the latter compared to diabetic subjects, but only in relation to 3 skin folds (tricipital, subscapular and suprailiac) and one circumference (forearm). CONCLUSIONS: The study shows a high frequency of overweight and obesity in children with type 1 diabetes, comparable to that in the healthy population. The finding of a higher frequency of obesity in diabetic females might be explained by their advanced puberal status, given that almost all the obese diabetic females were aged between 10 and 19 years old. The study confirms the validity of a number of anthropometric measurements (BMI, folds, circumference) and BIA in the evaluation of nutritional status in terms of body composition.

Adolescent↗
PubMed1998

Intracranial hypotension syndrome: neuroimaging in five spontaneous cases and etiopathogenetic correlations.

Intracranial hypotension (IH) is essential or, more frequently, secondary. This syndrome is characterized by severe postural headache and low opening cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this study five patients are investigated. Neuroimaging showed: on computerized tomography scan (CT), poor visualization of the cerebral sulci with small ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with enhancement on the convexity, along the tentorium and in the upper cervix after administration of contrast medium and downward displacement of the brain. Radionuclide cisternography was normal in the two patients who underwent this treatment as well as the meningeal biopsy in another patient. In all patients the opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously recovered contextually to normalization of neuroradiological findings. The possible pathogenesis (dural border cell layer tear) was discussed and the importance of diagnostic confirmation with MRI and measurement of CSF pressure when IH is thought to be present was underlined.

Adult↗
PubMed1998

Transient oculomotor cranial nerves palsy in spontaneous intracranial hypotension.

Transient sixth cranial nerves palsy may occur in rare cases after lumbar puncture, spinal anesthesia and myelography as well as in more rare cases of spontaneous intracranial hypotension. We report three cases of spontaneous intracranial hypotension with sixth cranial nerves palsy. One of these patients presented also third cranial nerve palsy, never reported in spontaneous intracranial hypotension.

Abducens Nerve↗
PubMed1997

Immunological and endocrinological abnormalities in paraneoplastic disorders with involvement of the autonomic nervous system.

We report a series of four patients in whom the onset of systemic cancer was heralded by dysautonomic symptoms and a neurological non-metastatic complication mediated by immunological and endocrine factors. The series includes: a patient with acute leukaemia and autonomic sensory-motor polyradiculoneuropathy, a patient affected by colon carcinoma and autonomic neuropathy and limbic encephalitis, a patient with lung cancer and autonomic neuropathy and hypercalcaemic encephalopathy, a patient with small cell lung cancer associated with autonomic neuropathy in Lambert-Eaton Myasthenic Syndrome (LEMS) and syndrome of inappropriate ADH secretion (SIADH). We underline the prognostic importance and discuss the possible etiopathogenetic role of autonomic dysfunction, which is frequently associated with paraneoplastic neurologic syndromes of autoimmune and/or dysendocrine origin.

Aged↗
PubMed1995

Primary intracranial hypotension: pathogenetic and neuroradiological considerations.

Primary or spontaneous intracranial hypotension (SIH) is a rare syndrome which causes postural headache associated with spinal fluid hypotension. We report three cases of SIH, characterised on magnetic resonance imaging (MRI) by pachymeningeal enhancement not only at cerebral level, but also in the cervical spinal cord, which subsequently resolved completely and spontaneously. We discuss the possible pathogenetic mechanisms of the dural alterations and underline the radiological aspects.

Adult↗