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Biomedical subjects

G Minniti

Publications and source records attributed to G Minniti.

At least 37 records · Page 2Linked to original sources
PubMed2000

Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency.

We describe a child with severe psychomotor retardation, peripheral neuropathy and bilateral abnormal signal in basal ganglia on magnetic resonance imaging, consistent with Leigh disease. Fibroblast pyruvate dehydrogenase assayed with routine method was normal. However, because of neurological improvement after treatment with thiamine, pyruvate dehydrogenase activity was studied again with thiamine pyrophosphate concentration adjusted to the normal human tissue level and found to be deficient. We report here on diagnostic difficulties and clinical follow-up of this patient.

Child↗
PubMed1999

Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients.

Cardiac involvement, mostly characterized by left ventricular hypertrophy associated with various degrees of cardiac dysfunction, greatly contributes to the increased mortality and morbidity observed in acromegaly. Lanreotide is a new SRIF analog characterized by a slow-release (SR) formulation with the peculiarity of a 30-mg im administration every 10-14 days. In this study, 13 patients with postoperative active acromegaly (9 females, 4 males, 45.9 +/- 16.3 yr old) underwent an echo-Doppler and hormonal study before and during a 12-month period of treatment with SR-lanreotide. GH and insulin-like growth factor I plasma levels (mean +/- SD) decreased significantly throughout the study period (from 10.1 +/- 2.2 to 3.9 +/- 0.9 ng/mL for GH, P < 0.005; and from 511.0 +/- 33.0 to 305.0 +/- 34.2 ng/mL for insulin-like growth factor I, P < 0.0001). Left ventricular mass index (mean +/- SD, 137.1 +/- 7.5 g/m2 at baseline) decreased after 3 months (120.0 +/- 5.4 g/m2), 6 months (111.7 +/- 5.7 g/m2), and 12 months (110.3 +/- 5.2 g/m2) of treatment (P < 0.005 at each time-point). This reduction in left ventricular mass index was accompanied by an improvement in some indexes of left ventricular diastolic function, especially the isovolumetric relaxation time (mean +/- SD, 109.1 +/- 4.6 m/sec at baseline), which decreased after 3 months (91.9 +/- 2.8 m/sec), 6 months (92.3 +/- 3.2 m/sec), and 12 months (92.2 +/- 3.0 m/sec) of treatment (P < 0.005 at each time-point). We conclude that SR-lanreotide is able to improve cardiac morphology and functional abnormalities in acromegaly; whether such beneficial effects on cardiac parameters will contribute to improve life expectancy in these patients should be further investigated.

Acromegaly↗
PubMed1999

The insulin-like growth factor binding protein superfamily: new perspectives.

The insulin-like growth factor (IGF) binding proteins (IGFBPs) were initially identified as carrier proteins for IGF-I and IGF-II in a variety of biologic fluids. Their presumed function was to protect IGF peptides from degradation and clearance, increase the half-life of the IGFs, and deliver them to appropriate tissue receptors. The concept of IGFBPs as simple carrier proteins has been complicated, however, by a number of observations: 1) the six IGFBPs vary in their tissue expression and their regulation by other hormones and growth factors; 2) the IGFBPs are subjected to proteolytic degradation, thereby altering their affinities for the IGFs; 3) IGFBP-3 and IGFBP-5, in addition to binding IGFs, also can associate with an acid-labile subunit, thereby increasing further the half-life of the IGFs; 4) in addition to modifying the access of IGF peptides to IGF and insulin receptors, several of the IGFBPs may be capable of increasing IGF action; 5) some of the IGFBPs may be capable of IGF-independent regulation of cell growth; 6) some of the IGFBPs are associated with cell membranes or possibly with membrane receptors; and 7) some of the IGFBPs have nuclear recognition sites and may be found within the nucleus. Additionally, a number of cDNAs identified recently have been found to encode proteins that bind IGFs, but with substantially lower affinities than is the case with IGFBPs. The N-terminal regions of the predicted proteins are structurally homologous to the classic IGFBPs, with conservation of the cysteine-rich region. These observations suggest that these low-affinity binders are members of an IGFBP superfamily, capable of regulating cell growth by both IGF-dependent and IGF-independent mechanisms.insulin-like growth factor, insulin-like growth factor binding proteins.

Humans↗
PubMed1998

Determination of plasma and serum homocysteine by high-performance liquid chromatography with fluorescence detection.

Determination of homocysteine in plasma or serum is becoming an important diagnostic procedure. Accurate, rapid and low cost methods for measuring homocysteine are therefore required. We have improved an HPLC method and made it suitable for clinical application. The total homocysteine in plasma consists of free homocysteine (i.e., reduced plus oxidized homocysteine in the non-protein fraction of plasma) and protein-bound homocysteine. The method consists of the following steps: reduction of the sample with tri-n-butylphosphine, precipitation of proteins with trichloroacetic acid (10%) and derivatization with ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate. The derivatives are separated by reversed-phase high-performance liquid chromatography followed by fluorescence detection. The concentrations (mean +/- S.D.) of total homocysteine in plasma from 77 normal subjects, 44 male and 33 female adults, were 8.4 +/- 2.15 and 7.1 +/- 1.18 mumol/l, respectively. Serum concentrations were 8.8 +/- 2.6 mumol/l in males and 7.6 +/- 1.5 mumol/l in females.

Chromatography, High Pressure Liquid↗
PubMed1998

Purines and pyrimidines determination in urine using high-performance liquid chromatography.

Single purine and pyrimidine bases are involved in two fundamental metabolic pathways that lead to formation of the building stones of DNA and RNA. Purine and pyrimidine nucleotides are also critically important metabolites in many cellular functions. The main breakdown of purines and pyrimidines produces uric acid and B-minoacids, respectively. Therefore, the study of purine and pyrimidine compounds in body fluid has high clinical relevance. We report, in this work, our experience in purines and pyrimidines determination in urine from children presenting with a clinical picture suggesting an inborn these pathways.

Biomarkers↗
PubMed1998

Visual improvement during octreotide therapy in a case of episellar meningioma.

Meningiomas of the tuberculum sellae can induce compression of the optic tract. We report the case of a 54-year-old female patient affected by a suspected pituitary macroadenoma with severe visual field defects, who experienced a significant clinical and visual improvement during short-term octreotide therapy, contrasting with the lack of neuroradiological evidence for tumor shrinkage. The patient subsequently underwent transcranial surgery with a final diagnosis of meningioma. The putative mechanisms of visual improvement during octreotide therapy are discussed.

Adenoma↗
PubMed1998

Echocardiographic evidence for a direct effect of GH/IGF-I hypersecretion on cardiac mass and function in young acromegalics.

OBJECTIVE: The interpretation of echocardiographic abnormalities in acromegalic patients is complicated by non-specific age-related diseases, many of which are commoner in acromegaly. We have therefore investigated the cause-effect relationship between GH/IGF-I hypersecretion and precocious cardiovascular abnormalities in a series of young acromegalic patients. DESIGN: An open prospective study. PATIENTS: 20 acromegalic patients aged under 30 years, with normal blood pressure and glucose tolerance, and 20 age-matched control subjects. MEASUREMENTS: Cardiac morphological parameters and indices of systolic and diastolic function at rest were studied by Doppler echocardiography. RESULTS: Left ventricular mass (LVM) and LVM index (LVMi) were higher in acromegalics than in control subjects (215.0 +/- 15.4 g vs 140.8 +/- 8.5 g, P = 0.0002 and 109.8 +/- 5.9 g/m2 vs 82.1 +/- 3.7 g/m2, P = 0.0008, respectively), reaching values of left ventricular hypertrophy in 4 patients (20%). Both ejection fraction and fractional shortening were normal (66.4 +/- 2.1% vs 62.2 +/- 1.9% and 37.5 +/- 1.5% vs 35.8 +/- 1.3%, respectively), indicating normal left ventricular systolic function. Abnormalities of left and right diastolic ventricular filling were found, which consisted of an increased isovolumic relaxation time (99.2 +/- 2.7 ms vs 89.0 +/- 2.7 ms, P = 0.01) and impaired mitral and tricuspidal flow velocity curves. CONCLUSIONS: An increase in cardiac mass and subclinical biventricular diastolic dysfunction were observed in young acromegalic patients. These findings argue for a direct cause-effect relationship between GH/IGF-I hypersecretion and myocardial abnormalities, and indicate that careful cardiological evaluation is mandatory in all acromegalics, whatever their age.

Acromegaly↗
PubMed1998

Epidermal growth factor binding sites in human pituitary macroadenomas.

The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with Kd1 = 0.62 +/- 0.23 nM and Kd2 = 53.8 +/- 8.2 nM for the high- and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10.2 fmol/mg membrane protein, range 0.0-332.0). EGF-receptor positivity, defined as EGF binding > or = 10.0 fmol/mg protein, was observed in 23 samples (54.8%), especially in prolactinomas (76.5%, P < 0.05 vs other tumors taken together) and in gonadotrope adenomas (62.5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12.8 vs 0.0 fmol/mg membrane protein, P = 0.047), and especially in adenomas invading the sphenoid sinus (median 26.7 fmol/mg membrane protein, P = 0.008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P = 0.15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.

Adenoma↗
PubMed1998

Prevalence of hypertension in acromegalic patients: clinical measurement versus 24-hour ambulatory blood pressure monitoring.

OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical measurement, with considerable variations reported concerning its prevalence in acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the prevalence of hypertension in patients with active acromegaly according to non-invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained with those provided by clinical measurement. PATIENTS: Forty patients with active acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included. Patients were in wash-out for antihypertensive treatment and none had been using any medical treatment for acromegaly for at least 3 months before the study. All were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as the mean of BP values obtained by standard sphygmomanometric measurement in three separate occasions. Mean 24-hour, daytime and night-time BP values were obtained by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values, the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus 136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus 88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were 137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being significantly lower than the corresponding clinical BP values (P < 0.0001). About 60% of the patients considered hypertensive by clinical measurement were found to be normotensive by ABPM, thereby decreasing the prevalence of hypertension in this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all patients defined as normotensive by clinical measurement were also normotensive by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower prevalence of hypertension in acromegalic patients then usually reported, suggesting that the role of hypertension in the pathogenesis of acromegalic cardiomyopathy is commonly overestimated. We propose that ambulatory blood-pressure monitoring should be routinely proposed in acromegalics with high or borderline clinical blood pressure values although it is not useful in patients defined normotensive according to repeated clinical measurement.

Acromegaly↗
PubMed1997

Spherophakia associated with molybdenum cofactor deficiency.

Molybdenum cofactor deficiency is an autosomal recessive disorder characterized by lack of activity of the enzymes sulfite oxidase, aldehyde oxidase, and xanthine dehydrogenase or oxidase. The clinical manifestations are indistinguishable from those of isolated sulfite oxidase deficiency: craniofacial alterations, intractable neonatal convulsions, very severe mental retardation, lens dislocation, and death in the first decade of life. Lens dislocation is found in nearly all patients after neonatal age. In the present case it developed late (at the age of 8 years) and was preceded by bilateral spherophakia. We hypothesize that an abnormal relaxation of the zonular fibers is the cause of spherophakia in this disease; this causes lens dislocation eventually, after days, months, or years.

Child↗
PubMed1997

Acute effects of octreotide, cabergoline and a combination of both drugs on GH secretion in acromegalic patients.

PURPOSE: The acute GH lowering effects of a single dose of either octreotide (OCT) or cabergoline (CAB), given alone and in combination, were studied in a series of 21 patients with acromegaly. PATIENTS AND METHODS: Plasma GH was measured for 8 hours after a single subcutaneous injection of OCT (100 micrograms) and for 48 hours after a single oral dose of CAB (0.5 mg) in all patients. Fourteen patients, who did not suppress GH levels below 5 micrograms/L after either OCT or CAB given alone, also received a combination of both drugs (OCT 100 micrograms s.c. + CAB 0.5 mg p.o. 24 h before OCT). RESULTS: GH levels were acutely suppressed by more than 50% in 15/21 cases after OCT alone and in 5/21 after CAB alone, respectively (P < 0.01). In the 14 patients who received the combined test, the magnitude of GH suppression was significantly higher than after OCT alone 4, 6 and 8 hours after OCT administration (P < 0.02). In patients with mixed GH/PRL-secreting tumors, the additive effect of OCT and CAB was observed at each time point. CONCLUSION: These results suggest that combined therapy with OCT and CAB may be more effective in suppressing GH secretion than either compound given alone, especially in patients with GH/PRL-secreting adenomas.

Acromegaly↗
PubMed1996

Macroprolactinomas as cause of delayed puberty. A report of two cases and effects of medical therapy.

About 3-5% of pituitary tumors occur in pediatric patients, often showing a considerable severity during childhood and puberty and major difficulties in their therapeutic management. As far as macroprolactinomas are concerned, surgery is often not resolutive, so that the need for postoperative treatment, consisting of either radiotherapy or bromocriptine, is the rule for tumors with extrasellar extension. In the present manuscript we report two cases of macroprolactinomas in adolescent patients suffering from delayed puberty, short stature and ocular symptoms together with hormonal levels indicating the presence of hypopituitarism. In both patients bromocriptine therapy showed a particular efficacy both in controlling tumor size and growth and in reducing clinical signs and symptoms. We conclude proposing DA-therapy as a first line of management in adolescents affected by macroprolactinomas, even in the presence of neurological symptoms.

Adolescent↗
PubMed1995

Idiopathic megarectum in adults. An assessment of manometric and radiologic variables.

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P = 0.02), minimum relaxation volume (P < 0.001), defecatory sensory threshold (P < 0.001), mean rectal tolerable volume (P < 0.001), and rectal compliance (P < 0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P < 0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P < 0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.

Adolescent↗