PubMed Health⌕ Search

Biomedical subjects

M Boscaro

Publications and source records attributed to M Boscaro.

At least 19 recordsLinked to original sources
PubMed2006

P450c17 deficiency: clinical and molecular characterization of six patients.

CONTEXT: The characteristics of P450c17 deficiency include 46,XY disorder of sex development, hypertension, hypokalemia, and lack of pubertal development. OBJECTIVE: To better understand this rare enzymatic deficiency, we analyzed the CYP17A1 gene in six affected patients. DESIGN AND PATIENTS: We examined six patients, five 46,XY, and one 46,XX (age 9-29 yr) with complete lack of masculinization (female infantile external genitalia, no uterus) and delayed puberty, respectively, and different degrees of hypertension. MAIN OUTCOME MEASUREMENTS: Genotype-phenotype correlation was measured. RESULTS: Four homozygote mutations were identified by direct sequencing of the CYP17A1 gene corresponding to an alanin 302-proline (A302P) exchange; the loss of lysine 327 (K327del); the deletion of glutamate 331 (E331del); and the replacement of arginine 416 with a histidine (R416H). Both P450c17 activities were abolished in all the mutant proteins, except one, when expressed in COS1 cells. The E331del-mutated P450c17 retained 17alpha-hydroxylase activity. The mutant proteins were normally expressed, suggesting that the loss of enzymatic activity is not due to defects of synthesis, stability, or localization of P450c17 proteins. CONCLUSION: These studies confirm lack of masculinization in 46,XY individuals as the pathognomic sign of the complete P450c17 deficiency. In XX individuals P450c17 deficiency should be considered in cases of delayed puberty. Age of onset and the severity of hypertension do not seem to be constant. Careful examination of long-term follow-ups in two of our patients suggested to us that estrogen treatment in P450c17-deficient patients might worsen the enzymatic defect, leading to aggravation of the hypertension.

Adolescent↗
PubMed2005

Raloxifene: bone and cardiovascular effects.

Raloxifene (RLX), a selective estrogen receptor modulator (SERM), is currently indicated for the prevention and treatment of post-menopausal osteoporosis. At present, RLX is evaluated in other areas of study that include the reduction of the risk of breast cancer and cardiovascular (CV) disease in post-menopausal women. This SERM acts as an estrogen agonist in the skeleton, on serum lipid metabolism and on a number of coagulation factors, while it is an estrogen antagonist in the breast and uterus. Although our current data are incomplete, RLX has a favourable risk-benefit safety profile and is one of the most promising medical agents not only for the prevention of osteoporosis, but also for a large number of other disorders in post-menopausal women.

Aged↗
PubMed2005

Potential indications for somatostatin analogs in Cushing's syndrome.

In recent years, somatostatin analogs have been proposed and used in the diagnosis and therapy in Cushing's syndrome (CS). In these last few years, the potential therapeutic effects of somatostain analogs have been studied in different aspects of CS. The strong expression of somatostatin receptors (SSTR) type 5 in human corticotroph cells and the demonstrated efficacy of SOM230, a novel multi-ligand somatostatin analog, in inhibiting ACTH release in vitro suggest that this new drug may be effective in the treatment of ACTH hypersecretion. Very preliminary in vivo results suggest that SOM230 could be a promising drug in medical therapy for patients with Cushing's disease (CD). Prolonged treatment and more data will be needed in order to evaluate its long-term therapeutic efficacy.

Adenoma↗
PubMed2004

Body composition, fat distribution and metabolic characteristics in lean and obese women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, has many features of metabolic syndrome and can be considered a metabolic disease. Approximately 50% of patients with PCOS are overweight or obese with abdominal fat accumulation. Some metabolic alterations and abdominal fat distribution have also been reported in lean women with PCOS. The aim of this study was to evaluate the effect, if any, of obesity on metabolic features, body composition and fat distribution in patients with PCOS. Body composition and abdominal fat distribution (evaluated by DEXA), waist circumference, blood pressure, lipid profile, glucose tolerance and homeostasis model assessment index were determined in 23 lean [mean age 23 +/- 5 yr, mean body mass index (BMI) 22 +/- 2 kg/m2] and 27 overweight-obese (mean age 21 +/- 5 yr, mean BMI 32 +/- 5 kg/m2) patients with PCOS and in 20 age- and weight-matched eumenorrhoic women. Patients exhibited slight but non-significant differences in metabolic parameters, waist circumference, blood pressure and total and abdominal fat content compared with weight-matched controls. None of the lean subjects suffered from metabolic syndrome according to the National Cholesterol Education Program--Adult Treatment Panel III (NCEP-ATPIII) criteria as opposed to 10 overweight-obese patients and three overweight-obese control subjects (37% and 33.3% of each subgroup, respectively). Our data do not show significant metabolic alterations in lean PCOS women. Results indicate that obesity seems to underpin the metabolic alterations exhibited by the overweight-obese patients. However, since women with PCOS are at increased cardiovascular risk, further studies are needed to evaluate metabolic alterations and body composition in these patients.

Adipose Tissue↗
PubMed2004

Chemical-physical properties of lipoproteins in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN), a psychosomatic disorder, has serious negative effects on multiple organs and systems of the human body. Anorexia nervosa usually runs a chronic course and is associated with significant morbidity and mortality. In order to elucidate the role played by lipids in AN, in the present study we compared the plasma lipid profile and the chemical-physical properties of lipoproteins obtained from subjects affected by AN. MATERIALS AND METHODS: The study was performed on lipoproteins of AN subjects and of age-matched healthy subjects used as controls. We tested the susceptibility to oxidative stress in vitro, the fatty acid content, the fluidity using 2-dimethylamino-(6-lauroyl)-naphthalene (Laurdan) and 1,6-difenil-1,3,5-esatriene (DPH) probes. RESULTS: Present results indicate that AN patients present a deep alteration of the composition and of chemical-physical properties in circulating lipoproteins, even in the absence of significant modifications to clinical metabolic parameters. A significantly decreased body mass index (BMI) was found in AN patients in comparison with controls. Anorexia nervosa patients showed a significant modification of phospholipids to protein ratio and a significantly increased percentage of unsaturated fatty acids compared with control subjects as well as a decreased fluidity, a significantly increased percentage of liquid-crystalline phase in VLDL, and a significantly reduced susceptibility to oxidative stress, more pronounced in LDL. CONCLUSIONS: These results confirm the hypothesis that anorexia is accompanied by changes of lipid metabolism in the central nervous system (CNS).

Adult↗
PubMed2004

Percutaneous therapy of varicocele: effects on semen parameters in young adults.

BACKGROUND: In spite of many years of debate, the impact of varicocele on male infertility is still controversial since its pathogenetic role on the impairment of semen quality has never been fully demonstrated. METHODS: In the present work, a series of 426 young adult males undergoing percutaneous treatment of varicocele were studied and semen parameters were evaluated at baseline and 12 months of follow-up. RESULTS: A significant increase in sperm cell concentration and a decrease in immotile spermatozoa were found after varicocele repair, but we failed to detect any significant positive change in progressive motility as well in sperm morphology after treatment. Similar results were also obtained when semen parameters were correlated with the degree of varicocele. CONCLUSION: Since a spontaneous improvement in semen quality has been mathematically established as a model of regression toward the mean, we conclude that the correction of varicocele in young adults is not a major indication when semen alteration is the only clinical problem.

Adult↗
PubMed2004

Life events in the pathogenesis of hyperprolactinemia.

OBJECTIVE: Little is known about the relationship between recent life events and onset of hyperprolactinemia, despite the well-known effect of acute psychological stress on prolactin levels in healthy subjects. Recent life events in patients with hyperprolactinemia compared with healthy controls were investigated. DESIGN: Case-control study. METHODS: Fifty-two consecutive patients with hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60 years) and 52 healthy subjects matched for socio-demographic variables were studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were diagnosed as suffering from idiopathic hyperprolactinemia. Patients with additional pathology or with high prolactin due to medications were excluded. All patients were interviewed by Paykel Interview for Recent Life Events while on remission after surgery or pharmacological treatment. The time period considered was the year preceding the first signs of hyperprolactinemia, and the year before interview for controls. RESULTS: Patients with hyperprolactinemia reported significantly more life events than control subjects (P<0.001). The same significant difference compared with controls applied to patients with (n=16) and without (n=36) depression. All categories of events (except events that were likely to be under the subject's control) were significantly more frequent. There were no significant differences between patients with prolactinoma (n=33) and those with idiopathic hyperprolactinemia (n=19). CONCLUSIONS: Within the complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our findings emphasize a potential role of emotional stress in either prolactin-secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life stress may have implications in clinical assessment (e.g. functional hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological treatment).

Adolescent↗
PubMed2004

Microalbuminuria, brain vasomotor reactivity, carotid and kidney arterial flow in Type 2 diabetes mellitus.

Diabetic microangiopathy produces widespread small vessel impairment which particularly affects renal glomeruli functions. Microalbuminuria is the earliest marker of microangiopathic kidney disease and has also recently been recognised as a marker of macroangiopathic cardiovascular involvement. To determine correlations between daily microalbuminuria, local microangiopathic kidney damage, systemic macroangiopathic involvement and functional brain microcirculation, 70 Type 2 diabetic subjects who were diagnosed more than 5 years ago underwent carotid (to determine index of macro- and microangiopathy) and interlobar kidney artery color Doppler (to determine microangiopathic involvement), transcranial Doppler (to determine alterations in brain vasomotor reserve), and evaluation of daily albumin excretion rate. All the indices of microcirculatory involvement in the kidney, brain and small vessels downstream-from the carotid arteries were closely related (for all p<0.001) but never correlated with the macroangiopathy index. Daily microalbuminuria correlated with all the micro- (p<0.0001) and macroangiopathic (p<0.005) Doppler indices. These findings confirm that microangiopathy is the main cause of the diabetic increase in the albumin excretion rate and support the view that microalbuminuria can be considered a powerful biomarker of widespread macroangiopathy. Our results suggest microalbuminuria may also identify cerebrovascular diabetic involvement, as it predicts both macroangiopathic carotid alteration and microvascular brain impairment.

Aged↗
PubMed2003

Idiopathic infertility: susceptibility of spermatozoa to in-vitro capacitation, in the presence and the absence of palmitylethanolamide (a homologue of anandamide), is strongly correlated with membrane polarity studied by Laurdan fluorescence.

Capacitation is a widely investigated process, which induces sperm plasma membrane changes resulting in its increased affinity for the zona pellucida. The fluorescent probe Laurdan, localized only within the plasma membrane of spermatozoa, is particularly useful to evaluate bilayer polarity in this part of the cell. According to a previous study, sperm membranes from oligozoospermic and some normozoospermic subjects (defined according to World Health Organization criteria), are characterized by low polarity (high Laurdan exGP(340)), while the spermatozoa from the remaining normozoospermic men show a larger polarity (low exGP(340)). In this paper, Laurdan was used to study membrane changes occurring during in-vitro capacitation, on sperm membranes from oligozoospermic and normozoospermic subjects. Results indicated that cells with high exGP(340) show a different susceptibility to Ca(2+)-induced capacitation in vitro, as compared with cells with low exGP(340). Palmitylethanolamide, physiologically present in human reproductive tracts, affects the time-course of in-vitro capacitation, increasing the rate of this process only in the cells with a lower membrane polarity.

Cell Membrane↗
PubMed2003

Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors.

A 56-yr-old woman was referred with a diagnosis of Cushing's disease. Hypertension and severe hypokalemia were present and high urinary free cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and octreotide scans were negative. Remission and relapse periods lasting 3-4 months were observed during the 3.5 yr of follow-up. Finally a thoracic computed tomography scan showed a basal paracardic nodule in the left lung. After surgery, a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was diagnosed, staining positively for ACTH. RT-PCR revealed expression of proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue. Interestingly, we observed the simultaneous presence of ghrelin and both GH secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting tumor with an in vivo ACTH response to hexarelin coupled with the tumoral expression of ghrelin and GHS receptors. This finding might imply an autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting tumors.

Bronchial Neoplasms↗
PubMed2003

Diagnosis and complications of Cushing's syndrome: a consensus statement.

In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Cardiovascular Diseases↗
PubMed2001

Cushing's syndrome.

During the past 30 years, there have been advances in understanding of the pathogenesis of Cushing's syndrome and in differential diagnosis of its various forms. Improved diagnostic tests and procedures have increased the ability to recognise even mild hypercortisolism and have provided the means to obtain an accurate diagnosis. Despite these advances, the occurrence of unusual clinical presentations and laboratory shortcomings may produce diagnostic problems and challenge clinical intuition. This article reviews recent pathogenic views, new tests, and new diagnostic problems in the evaluation of Cushing's syndrome. Atypical clinical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome are also reported.

Cushing Syndrome↗
PubMed2001

Recovery of bone mineral density after surgical cure, but not by ketoconazole treatment, in Cushing's syndrome.

The aim of our study was to retrospectively assess the effect of treatment on bone mineral density (BMD) in patients with Cushing's syndrome. Nineteen patients (17 women, 2 men; mean age +/- SD, 41 +/- 10 years; preoperative duration of disease 20 +/- 15 months) were studied. Six patients had a cortisol-producing adenoma and 13 had pituitary-dependent bilateral adrenal hyperplasia. BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry just before and 1-10 years after adrenalectomy or pituitary adenomectomy. Patients were divided in two groups. The first group of 9 patients (6 adrenal and 3 pituitary adenomas; group A) included those treated successfully by surgery ( > 5 years follow-up in the case of pituitary surgery). The second group of 10 patients (group B) included those treated with the steroidogenesis inhibitor ketoconazole, 300-600 mg/day, after unsuccessful pituitary surgery. In group A, restoration of normal cortisol was associated with a significant increase in BMD (from 829 +/- 112 mg/cm2 to 952 +/- 107 mg/cm2; p = 0.002). In group B, no changes in BMD were observed (from 857 +/- 160 to 847 +/- 163 mg/cm2), in spite of markedly decreased or normalized cortisol levels during ketoconazole treatment. These findings indicate that definitive correction of hypercortisolism restores BMD to normal levels in patients with Cushing's syndrome. In patients treated with ketoconazole after unsuccessful pituitary surgery, even when normalization of cortisol levels was achieved, BMD remained low. This would suggest an interfering effect of this drug on bone metabolism.

Absorptiometry, Photon↗
PubMed2001

Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.

OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.

Adrenal Gland Neoplasms↗