Biomedical subjects

Giovanni Vitale

Publications and source records attributed to Giovanni Vitale.

31 records · Page 2Linked to original sources

PubMed2004

Prolactin and prostate hypertrophy: a pilot observational, prospective, case-control study in men with prolactinoma.

In experimental models, prolactin (PRL) displays independent hypertrophic effects on the prostate. To investigate whether hyperprolactinemia is associated with prostate enlargement in humans, we designed this open, prospective, case-control study enrolling 20 men with prolactinoma (aged 34 +/- 10 yr) and 20 age-matched healthy men. The endocrine profile and prostate transrectal ultrasonography were performed before and after 12 and 24 months of cabergoline treatment in the patients and at study entry and after 24 months in the controls. The patients had lower serum testosterone, dihydrotestosterone (DHT), and IGF-I levels and prostate volume (15.4 +/- 3.5 vs. 19.6 +/- 5.1 ml; P < 0.001) and higher PRL levels and prostate-specific antigen density than controls. There was no difference in prostate and transitional zone volumes between patients with normoandrogenemia (n = 8) or hypoandrogenemia (n = 12). After 12 and 24 months of treatment, PRL, testosterone, and DHT levels were normal in all cases, as were IGF-I and IGF-binding protein-3 levels. After 24 months, prostate volume was comparable to that in controls (21.7 +/- 4.5 vs. 22.5 +/- 4.7 ml). There were no changes in prostate structure throughout the study period in either the patients or the controls. In conclusion, in young men with prolactinoma PRL excess is unlikely to have effects on the prostate per se, because it is accompanied by low testosterone and DHT levels that produce the major effects.

Adult↗

PubMed2004

Cardiac abnormalities in acromegaly. Pathophysiology and implications for management.

Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.

Acromegaly↗

PubMed2004

Alpha-interferon and its effects on signalling pathways within cells.

Interferon-alpha (IFNalpha) is a recombinant protein widely used in the therapy of several neoplasms such as myeloma, renal cell carcinoma, epidermoid cervical and head and neck tumours and melanoma. IFNalpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of cancer cell growth and differentiation, affecting cellular communication and signal transduction pathways. However, the way by which tumour cell growth is directly suppressed by IFNalpha is not well known. Wide evidence exists on the possibility that cancer cells undergo apoptosis after the exposure to the cytokine. Here we will review the consolidate Signal transducer and activator of transcription (STAT)-dependent mechanism of action of IFNalpha and the supposed mechanism of apoptosis induction by IFNalpha. We will discuss data obtained by us and others on the triggering of the stress-dependent kinase pathway and on the modulation of protein synthesis machinery induced by IFNalpha and their correlations with the apoptotic process. Until today, inconsistent data have been obtained regarding the clinical effectiveness of IFNalpha in the therapy of solid tumours. In fact, the benefit of IFNalpha treatment is limited to some neoplasms while others are completely or partially resistant. The mechanisms of tumour resistance to IFNalpha have been studied in vitro. The alteration of JAK- Signal transducer and activator of transcription components of the IFNalpha-induced signalling, can be indeed a mechanism of resistance to IFN and cross talks between IFNalpha and survival signals has been also described. However, we have recently described a reactive mechanism of protection of tumour cells from the apoptosis induced by IFNalpha dependent on the epidermal growth factor (EGF)-mediated Ras/extracellular signal regulated kinase (Erk) signalling. The involvement of the Ras->Erk pathway in the protection of tumour cells from the apoptosis induced by IFNalpha is further demonstrated by both Ras inactivation by RASN17 transfection and mitogen extracellular signal regulated kinase 1 (Mek-1) inhibition by exposure to PD098059. These data strongly suggest that the specific disruption of the latter could be a useful approach to potentiate the antitumour activity of IFNalpha against human tumours based on the new mechanistic insights achieved in the last years.

Apoptosis↗

PubMed2004

Usefulness of pulsed tissue Doppler for the assessment of left ventricular myocardial function in overt hypothyroidism.

BACKGROUND: The aim of this study was to assess the role of tissue Doppler (TD) in the identification of left ventricular (LV) myocardial regionl abnormalities in overt hypothyroidism. METHODS: Fourteen women with newly diagnosed, never treated overt hypothyroidism and 14 healthy women, matched for age, underwent standard echocardiography and pulsed TD, by placing the sample volume at the basal posterior septum and lateral mitral annulus, in the apical 4-chamber view. The myocardial systolic (SM) and diastolic velocities (Em, Am and their ratio) and time intervals (relaxation time [RTm], pre-contraction time [PCTm], contraction time) were measured. RESULTS: The two groups were comparable for body surface area, blood pressure and heart rate. At standard echocardiography, patients with overt hypothyroidism had a significantly greater septal thickness and LV mass index, a longer LV pre-ejection period (PEP), deceleration time and isovolumic relaxation time (IVRT) and a lower E peak velocity and E/A ratio. TD showed a significantly longer PCTm and RTm and a lower Em and Em/Am ratio of both the septum and mitral annulus in overt hypothyroidism. The ratio of the standard Doppler E to Em of the mitral annulus was 5.5 +/- 1.2 in controls and 5.3 +/- 1.7 in overt hypothyroidism (p = NS). In the overall population, PEP, IVRT, PCTm and RTm were correlated negatively with FT3 and FT4, and positively with thyroid-stimulating hormone. After adjusting for age, body surface area and heart rate in separate multivariate analyses, the associations of TD PCTm with the thyroid hormones and thyroid-stimulating hormone were greater than the homologous associations of standard Doppler PEP. CONCLUSIONS: Standard echocardiography confirms itself as a satisfactory diagnostic technique for the identification of LV global dysfunction in overt hypothyroidism. Pulsed TD may be useful to determine the severity of LV myocardial dysfunction in relation to the degree of hormonal impairment.

Adult↗

PubMed2003

Ultrasound-guided laser thermal ablation in the treatment of autonomous hyperfunctioning thyroid nodules and compressive nontoxic nodular goiter.

OBJECTIVE: Percutaneous laser thermal ablation (LTA) has been applied in several tumors. In this study we evaluated the safety and long-term efficacy of LTA in the treatment of benign thyroid nodules. DESIGN AND PATIENTS: Seven patients with autonomous hyperfunctioning thyroid nodule (group A) and five patients with compressive nodular goiter (group B) were treated with LTA. Up to three needles were positioned centrally in the thyroid nodule and laser fiber was placed in the lumen of the needle. Laser illumination was performed reaching a maximal energy deposition of 1800 J per fiber. MEASUREMENTS: Thyroid nodule volume, endocrinologic, and clinical evaluation were performed at baseline, 3, and 12 months after the treatment. Scintigraphy was performed at diagnosis and 12 months after the first session in group A. RESULTS: In group A, mean thyroid volume decreased from 3.15 +/- 1.26 mL to 0.83 +/- 0.49 mL (p < 0.001) after 12 months. The treatment induced disappearance of clinical signs and symptoms related to hyperthyroidism; normalization of free triiodothyronine (FT(3)), free thyroxine (FT(4)), and thyrotropin (TSH) serum levels and recovery of extranodular uptake at scintiscan. In group B, mean thyroid volume decreased from 11.14 +/- 4.99 mL to 3.73 +/- 1.47 mL (p < 0.01) after 12 months. Pressure symptoms in the neck, difficulty in swallowing and tracheal displacement improved in all patients. The treatment was well tolerated in both groups of patients. CONCLUSIONS: LTA appears to be a valid and safe alternative approach in the treatment of benign thyroid nodules.

Adult↗

PubMed2003

Lethal systemic capillary leak syndrome associated with severe ventilator-induced lung injury: an experimental study.

OBJECTIVE: We report the evolution of severe ventilator-induced lung injury associated with lethal systemic capillary leak syndrome, when sheep were ventilated at a peak inspiratory pressure of 50 cm H2O, at a respiratory rate of 8 breaths.min, with an inspiratory time of 2.5 secs. DESIGN: A prospective laboratory animal study. SETTING: Experimental animal research laboratory. SUBJECTS: Mixed breed sheep. INTERVENTIONS: Sheep were anesthetized, paralyzed, and mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: This sheep model was characterized by a rapidly evolving massive anasarca, hemoconcentration, cardiac dysfunction, multiple system organ failure, and severe ventilator-induced lung injury. Cardiovascular changes and profound hemoconcentration developed within 6 hrs from the start of mechanical ventilation, along with a major decline in pulmonary compliance and deterioration in arterial blood gases. When total static lung compliance decreased to 0.15 mL (cm H2O)(-1) x kg(-1) (7-30 hrs), the sheep were randomized to two groups. Group I received high (recruitive) positive end-expiratory pressure (9-20 cm H2O), adjusted as needed; group II received low (supportive) positive end-expiratory pressure (2-6 cm H2O). Sheep in both groups progressively deteriorated and died with cardiocirculatory failure and multiple system organ failure within 12-24 hrs from start of treatment. CONCLUSIONS: This model of lethal systemic capillary leak syndrome with multiple system organ failure differs greatly from our previous sheep model of acute ventilator-induced lung injury in which sheep were ventilated with a peak inspiratory pressure of 50 cm H2O, a respiratory rate of 4 breaths x min(-1), and an inspiratory time of 1.35 secs, without inducing capillary leak syndrome. The mere change of respiratory rate from 4 to 8 breaths x min(-1), with a near doubling of the inspiratory time to 2.5 secs, although maintaining eucapnia, resulted in lethal systemic capillary leak syndrome and multiple system organ failure with both gross and microscopic pathology of lungs greatly different from our previous model of mechanical ventilation-induced acute respiratory distress syndrome.

Animals↗

PubMed2003

Influence of body surface area on serum peak thyrotropin (TSH) levels after recombinant human TSH administration.

Recombinant human TSH (rhTSH) has been proposed as an alternative method to the withdrawal of thyroid hormones in the follow-up of differentiated thyroid cancer. The aim of the present study was to evaluate the influence of several demographic and anthropometric parameters [age, body weight, height, body mass index, and body surface area (BSA)] on serum peak TSH levels after rhTSH administration. rhTSH was administered to 112 patients with differentiated thyroid carcinoma according to the conventional two-dose schedule (0.9 mg/d). Serum TSH levels were measured 24 h before and after the first administration of rhTSH, and then 24, 48, and 72 h after the second administration of rhTSH. In one severely obese patient, serum peak TSH values did not reach a valid stimulation range. Serum peak TSH levels were negatively related to body weight (r = -0.69; P < 0.0001), body mass index (r = -0.51; P < 0.0001), and BSA (r = -0.72; P < 0.0001). In a multivariate regression analysis including demographic and anthropometric variables, only BSA was independently associated to serum peak TSH concentrations (standardized beta coefficient = -0.721; P < 0.0001). In conclusion, body size seems to influence serum peak TSH levels after rhTSH administration. Future studies should evaluate the possibility of using personalized rhTSH doses, adjusted in relation to BSA.

Adolescent↗

PubMed2003

High prevalence of cardiac valve disease in acromegaly: an observational, analytical, case-control study.

To characterize mitral and aortic valve abnormalities we performed M-mode, two-dimensional, and pulsed Doppler echocardiography in 42 patients with active acromegaly, 22 patients cured of acromegaly, and 64 controls pair-matched with the patients for sex and age. The overall prevalence of valve abnormalities was higher in both the active patients (86% vs. 24%; P < 0.0001) and the cured patients (73% vs. 9%; P < 0.0001) than in controls. Left ventricular hypertrophy was higher in active (81% vs. 29%; P < 0.0001), but not in cured (41% vs. 14%; P = 0.09) patients than in controls. Cardiac valve abnormalities were associated with left ventricular hypertrophy in both patients and controls, without any difference between them. Conversely, among subjects without left ventricular hypertrophy, mitral and aortic abnormalities were only present in the patients (75% of active and 54% of cured), but not in controls (3% of active controls and 0% of cured controls). In conclusion, patients with active acromegaly and those cured of the disease have a high prevalence of mitral and aortic abnormalities. The persistence of valve disease in patients with cured acromegaly is likely to be correlated with the persistence of left ventricular hypertrophy, which should be carefully and continuously monitored as an aspect of the risk of cardiac dysfunction in these patients.

Acromegaly↗

PubMed2003

Influence of growth hormone on cardiovascular health and disease.

Experimental and clinical studies indicate that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are involved in heart development. Impaired cardiovascular function, as recently demonstrated, could potentially reduce life expectancy both in GH deficiency (GHD) and excess. Patients with childhood- or adult-onset GHD may have both cardiac structural and functional abnormalities, i.e. reduced cardiac mass, reduced diastolic filling, and impaired left ventricular response to peak exercise. In addition, GHD patients may present with an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques that can further aggravate the hemodynamic conditions and contribute to the increased cardiovascular and cerebrovascular risk. However, some evidence has been provided to show that cardiovascular abnormalities can be partially reversed after somatropin (recombinant GH) therapy in patients with GHD. Recently, somatropin administration was shown to induce improvement in hemodynamics and clinical status in some patients with heart failure. Although these data need to be confirmed in more extensive studies, such promising results open new perspectives for somatropin therapy. The role of GH secretagogues in heart failure is still unknown.

Animals↗

PubMed2002

Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension.

BACKGROUND: The reduction of coronary flow reserve (CFR) found in arterial hypertension may be due to changes in afterload, left ventricular (LV) structure, and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be associated with the magnitude of CFR in relation to its modulating action on cardiac and endothelial function. METHODS: A total of 44 newly diagnosed, untreated hypertensive patients, who were free of diabetes mellitus and coronary artery disease, underwent M-mode analysis, second-harmonic Doppler echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg intravenously in four patients), determination of circulating free IGF-1, and insulin resistance. Based on CFR levels, hypertensive subjects were divided into two groups: 18 with normal CFR (> or = 2) and 26 with impaired CFR (<2). RESULTS: Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV mass index but higher free circulating IGF-I than patients with reduced CFR (P < .001). Insulin resistance was not significantly different between the two groups. In a first multilinear regression analysis that included demographic and echocardiographic variables, insulin resistance was independently associated with CFR (standardized beta coefficient = -0.31, P < .05) in the overall population. However, in a subsequent model which included also IGF-1, the relationship between insulin resistance and CFR disappeared, whereas IGF-1 was the main independent determinant of CFR (beta = 0.51, P < .0002). CONCLUSIONS: Free IGF-1 circulating levels are independently associated with CFR in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.

Adult↗

PubMed2002

Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes.

Male Wistar rats were treated with ondansetron (1 and 2 mg/kg s.c.), ketanserin (0.2, 1 and 5 mg/kg s.c.) or NAN-190 (1, 3 and 5 mg/kg i.p.) 15 min before acetylsalicylic acid (ASA, 400 mg/kg i.p.), and 30 min thereafter the pain threshold was evaluated. The antinociceptive activity of ASA in the hot-plate test was variously affected by ondansetron, ketanserin and NAN-190: at the highest dose (2 mg/kg s.c.) ondansetron abolished it while ketanserin (5 mg/kg s.c.) significantly reduced it, and NAN-190 (1-5 mg/kg) did not significantly modify the effect of ASA. Binding experiments indicate that both ondansetron and ketanserin completely prevented the decrease in the maximum number of 5-HT(2) receptors (B(max)) provoked by ASA. These data indicate that the central antinociceptive activity of ASA is modulated in a different manner by serotonin receptor antagonists, and that 5-HT(2) and 5-HT(3) receptors may exert a pivotal role in nociception, alone or in association.

Analgesics, Non-Narcotic↗

PubMed2002

Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler.

Pulsed tissue Doppler (TD) is a new ultrasound tool that allows quantification of myocardial regional wall motion. To investigate the cardiac effects of subclinical hypothyroidism (SH), the present study assessed left ventricular (LV) myocardial regional function in SH by pulsed TD. Twenty women with SH and 20 healthy women underwent standard Doppler echocardiograms and pulsed TD, placing a sample volume at the level of posterior septum and LV mitral annulus. Myocardial systolic and diastolic velocities and time intervals were determined for both levels. Doppler-echocardiographic and TD measurements were adjusted for body surface area and heart rate. Standard Doppler showed an increases in LV preejection period, preejection period/LV ejection time ratio, and isovolumic relaxation time (IVRT) in SH. By TD analysis, myocardial precontraction time (PCT(m)), PCT(m)/myocardial contraction time ratio, and myocardial relaxation time (RT(m)) were prolonged at the level of both posterior septum and mitral annulus in SH. In the whole population, IVRT, PCT(m), and RT(m) were negatively related to FT(4), whereas IVRT, PCT(m)/myocardial contraction time ratio, and RT(m) were positively correlated to TSH. In conclusion, this study underscores the usefulness of TD to detect cardiac functional abnormalities due to stable SH, mainly by changes in myocardial time intervals in several LV segments.

Adult↗

PubMed2002

Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin.

BACKGROUND: Provocative tests for calcitonin (CT) are fundamental in the diagnosis and follow-up of C-cell disease and in the detection of hereditary medullary thyroid carcinoma (MTC) carriers with unknown RET mutations. A recent report has proposed omeprazole, which can increase endogenous gastrin (GT), as a new provocative test for MTC. METHODS: We compared the omeprazole test (20 mg twice a day for 4 days) to the pentagastrin test (0.5 microg/kg of body weight) for the diagnosis and management of MTC. Twenty healthy individuals and 20 MTC patients with mildly or moderately increased basal CT serum concentrations underwent the pentagastrin and omeprazole tests. RESULTS: In MTC patients, the pentagastrin test produced a significantly higher increase in serum CT than did omeprazole. After the pentagastrin injection, several patients reported unpleasant side effects, including substantial tightness in 38 of 40 participants. No adverse effects were observed during the omeprazole test. A significant direct correlation was recorded between CT% (ratio of CT peak to basal value x 100) and GT% (ratio of GT peak to basal value x 100) during the omeprazole test in MTC patients (r = 0.73; P <0.001). CONCLUSIONS: In spite of several adverse effects, pentagastrin remains the best provocative test for the diagnosis of MTC. Omeprazole may be useful when pentagastrin is contraindicated or refused because of the unpleasant side effects, but further validation is needed.

Adolescent↗