Daniela Pasquali | Università della Campania Luigi Vanvitelli (original) (raw)
Papers by Daniela Pasquali
Surgical Innovation, 2015
Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-... more Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy. Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications. Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P < .0001) versus the other 3 treatments. Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.
European Journal of Inflammation
Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic ... more Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic atrophic gastritis (AIG). Hypergastrinemia, secondary to AIG, predisposes to gastric enterochromaffin-like cell (ECL) hyperplasia, a preneoplastic condition. We evaluated the prevalence of AIG, hypergastrinemia and ECL hyperplasia in HT patients. A secondary end-point was to assess the efficacy of treatment with a somatostatin analogue in HT patient with ECL hyperplasia. From 2009 to 2011, 146 HT patients were enrolled in a prospective study. All cases underwent hormonal profile, and parietal cell antibody (PCA), gastrin, and chromogranin A (CgA) serum level assays. Selected patients with elevated gastrin and CgA levels underwent gastro esophageal endoscopy (EGDS). Patients positive for ECL hyperplasia received Octreotide LAR 30 mg/ 28 days for 12 months. Gastrin and CgA assays were repeated every three months and EGDS after one year. The results show that gastrin and CgA were significantly higher than normal in 17/115 (14.7%) patients. Seven more HT had isolated PCA positivity and in the 17 PCA positive patients histology diagnosed AIG, corpus prevalent, with mild to moderate atrophy. Diffuse ECL hyperplasia of the gastric body was present in three subjects, one of them presenting a type-1 carcinoid. Gastrin and CgA levels were significantly reduced (p<0.01) after 3 months of therapy with a somatostatin analogue and returned to normal after 1 year. ECL hyperplasia regressed in all three patients. We suggest that selected HT patients may need a more accurate surveillance for early signs of gastric EC risk. In the case of altered values of gastrin and in the presence of PCA positivity, EGDS and histology should be performed for an early diagnosis of AIG and treatment of ECL hyperplasia.
Il Giornale di chirurgia
to evaluate the role of pre and post-operative oral calcium and vitamin D supplements in preventi... more to evaluate the role of pre and post-operative oral calcium and vitamin D supplements in prevention of hypocalcemia after total thyroidectomy. 50 consecutive patients, undergoing total thyroidectomy, were enrolled. Oral calcium and vitamin D were administered in the pre and post-operative time. The data concerning symptomatic and laboratoristic hypocalcemia were collected. Incidence of symptomatic hypocalcemia was very low (6%); incidence of laboratoristic hypocalcemia was 10%. No permanent hypocalcemia developed. Implementing oral calcium and vitamin D both before and after total thyroidectomy can reduce the incidence of hypocalcemia related to surgery.
Journal of Cellular and Molecular Medicine, 2015
CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms... more CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1.
Journal of endocrinological investigation, 2003
In humans, like as in other mammals, the gonads, the internal genital ducts, and the external gen... more In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for diffe...
Minerva endocrinologica, 2001
Somatostatin (st) exerts a role in the control of prostate growth and function acting both at hyp... more Somatostatin (st) exerts a role in the control of prostate growth and function acting both at hypothalamus-hypophysis level and at glandular level. St analogues have been used to control prostate cancer (CaP) in clinical trials, with contradictory results. These data may be interpreted on the basis of st mechanism of action and tissue distribution of the five st receptors (sst1-5). Sts have been found in prostate tissue and, specifically, in the epithelial component. sst2 is preferentially expressed on normal prostate, sst1 and sst5 on CaP. st inhibits the proliferation of LNCaP and octreotide normal prostate epithelial cells in primary cultures. The lack of sst2 in CaP may explain the ineffectiveness of some selective st analogues in clinical trials. The use of other analogues actually developed with high affinities to ssts expressed mainly in CaP may represent a more rational approach.
Journal of pediatric endocrinology & metabolism : JPEM, 1998
We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudoher... more We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male ps...
Minerva endocrinologica, 1993
The American journal of physiology, 1990
Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid... more Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with an...
Molecular pharmacology, 1992
The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphos... more The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity of membrane preparations by approximately 40%. This inhibition was reversed by atropine, occurred even in a Ca(2+)-free medium containing ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, and was not reproduced by the Ca2+ ionophore A23187. The carbachol effect was not prevented by simultaneous incubation of cells with either isobutylmethylxanthine, an inhibitor of phosphodiesterase, or H-7, an inhibitor of protein kinase. Pretreatment of cells with pertussis toxin to inactivate the Gi inhibitory protein also failed to affect the carbachol inhibition. Although carbachol did not reduce the basal or the TSH-stimulated cyclase activities when ad...
Klinefelter's syndrome (KS) is the most common sex-chromosome male disorder, characterized by one... more Klinefelter's syndrome (KS) is the most common sex-chromosome male disorder, characterized by one or more extra X chromosomes. It is associated with a significant increase of cardiovascular mortality and morbidity. This review examines cardiovascular (CV) abnormalities known in KS until now. KS is associated with both functional and structural CV alterations, particularly KS patients show a wide range of CV abnormalities, specifically LV diastolic dysfunction, impaired exercise performance, Chronotropic Incompetence (CI), and increased carotid intima-media thickness (IMT). Regarding diastolic function, they display an increased Isovolumetric Relaxation Time (IVRT) but no prolongation of Mitral deceleration Time (MdT). This condition indicates the presence of a mild diastolic dysfunction. KS patients also have an exercise intolerance, that depends on reduced stroke volume during exercise, caused by the limited increase in the LV end-diastolic volume despite normal ejection fraction and the increased LV filling pressure and left atrial pressure during exercise. Patients with KS also display a significant increase of carotid IMT, a surrogate marker of atherosclerotic disease. This alteration represents a subclinical marker of early atherosclerosis and is the most important risk factor of new or recurrent stroke and myocardial infarction. Testosterone replacement Klinefelter's syndrome and cardiovascular disease therapy does not normalize the impaired cardiovascular parameters. This wide range of CV abnormalities represents the pathophysiological underpinnings for the raised mortality observed in KS.
Advances in Experimental Medicine and Biology, 1989
Systems Biology in Reproductive Medicine, 1993
Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. ... more Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. This study deals with the sixth recorded family with familial testicular torsion and the effects on the spermatogenesis and the appearance of testicular autoantibodies in three affected subjects (two brothers, aged 18 and 15 years, and their father, aged 48 years). The father and one of the brothers, who had peripubertal unilateral testicular torsion, presented normal fertility and oligozoospermia, respectively. The other brother, who had a history of bilateral testicular torsion, did not present pubertal development until he was 18 years old and he needed substitutive testosterone therapy. Sperm autoantibody titer increased only in the two cases with unilateral torsion and remained unmodified at a 5-year follow-up. The results indicate that testicular torsion can cause variable degrees of spermatogenesis impairment and induce development of autoantibodies against spermatozoa and gonadal antigens. The persistence of fertility in the father and the progressive spermatogenesis recovery in one of the affected sons suggest that the damaging effects of these autoantibodies deserve further investigation.
The Journal of Urology, 1998
Purpose: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group o... more Purpose: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group of cryptorchid boys, and determined whether it may be influenced by orchiopexy.
British Journal of Plastic Surgery, 2003
An increased secretion of cytokines and growth factors has been hypothesised to play a role in th... more An increased secretion of cytokines and growth factors has been hypothesised to play a role in the abnormal growth of keloid fibroblasts. The aim of this study was to evaluate the effect of the calcium antagonist verapamil on the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, as well as on cellular growth, in primary cultures of fibroblasts derived from the central part of keloid lesions. These cells grew faster than peripheral keloid and nonkeloid fibroblasts, and, in long-term cultures, became stratified assuming a three-dimensional structure. Compared with peripheral and nonkeloid fibroblasts, central keloid fibroblasts presented an increased production of both IL-6 and VEGF (P , 0.03 and P , 0.005, respectively). Verapamil (100 mM) decreased IL-6 and VEGF production (P , 0.03 and P , 0.005, respectively) in central keloid fibroblasts cultures at 72 h. Moreover, verapamil decreased cellular proliferation by 29% and increased apoptosis to an absolute value of 8%. The results of this study demonstrate that in primary cultures of central keloid fibroblasts verapamil reduces the sustained basal IL-6 and VEGF production and inhibits cell growth; these data may offer the link with the beneficial effect of calcium antagonists on keloid scars in vivo.
Journal of Molecular Endocrinology, 2000
Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. W... more Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-rastransformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10 7
Journal of Molecular Endocrinology, 2000
To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in ... more To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst 1-5 ) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [ 125 I-Tyr 11 ]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst). The sst 2 transcript was found in nine, sst 3 in five and sst 5 in eight out of ten GO cell cultures. Sst 2 was detected in all six, and sst 3 in four out of the six control cell cultures. Sst 4 was absent from all samples, and sst 1 was found only in six out of the ten GO samples.
Journal of Endocrinological Investigation, 2004
Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medul... more Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism due to specific RET proto-oncogene mutations. Fertile MEN 2A women are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. This condition may cause psychological distress in affected pregnant patients and their families. Here we describe the genetic prenatal testing, the pregnancy management and obstetric outcome in a MEN 2A patient with a right side adrenal hyperplasia and elevated calcitonin levels, a condition suspicious for possible recurrence of pheochromocytoma. We confirm that maternal or fetal complications are rare when MEN 2A diagnosis is made before pregnancy and an accurate monitoring is instituted. Furthermore, our results indicate that prenatal testing for RET mutations is highly recommended in making decisions and assuring parents on the lifelong risk of tumors. This will avoid the psychological distress that can further complicate the pregnancy of affected women.
Surgical Innovation, 2015
Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-... more Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy. Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications. Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001) versus the other 3 treatments. Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.
European Journal of Inflammation
Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic ... more Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic atrophic gastritis (AIG). Hypergastrinemia, secondary to AIG, predisposes to gastric enterochromaffin-like cell (ECL) hyperplasia, a preneoplastic condition. We evaluated the prevalence of AIG, hypergastrinemia and ECL hyperplasia in HT patients. A secondary end-point was to assess the efficacy of treatment with a somatostatin analogue in HT patient with ECL hyperplasia. From 2009 to 2011, 146 HT patients were enrolled in a prospective study. All cases underwent hormonal profile, and parietal cell antibody (PCA), gastrin, and chromogranin A (CgA) serum level assays. Selected patients with elevated gastrin and CgA levels underwent gastro esophageal endoscopy (EGDS). Patients positive for ECL hyperplasia received Octreotide LAR 30 mg/ 28 days for 12 months. Gastrin and CgA assays were repeated every three months and EGDS after one year. The results show that gastrin and CgA were significantly higher than normal in 17/115 (14.7%) patients. Seven more HT had isolated PCA positivity and in the 17 PCA positive patients histology diagnosed AIG, corpus prevalent, with mild to moderate atrophy. Diffuse ECL hyperplasia of the gastric body was present in three subjects, one of them presenting a type-1 carcinoid. Gastrin and CgA levels were significantly reduced (p<0.01) after 3 months of therapy with a somatostatin analogue and returned to normal after 1 year. ECL hyperplasia regressed in all three patients. We suggest that selected HT patients may need a more accurate surveillance for early signs of gastric EC risk. In the case of altered values of gastrin and in the presence of PCA positivity, EGDS and histology should be performed for an early diagnosis of AIG and treatment of ECL hyperplasia.
Il Giornale di chirurgia
to evaluate the role of pre and post-operative oral calcium and vitamin D supplements in preventi... more to evaluate the role of pre and post-operative oral calcium and vitamin D supplements in prevention of hypocalcemia after total thyroidectomy. 50 consecutive patients, undergoing total thyroidectomy, were enrolled. Oral calcium and vitamin D were administered in the pre and post-operative time. The data concerning symptomatic and laboratoristic hypocalcemia were collected. Incidence of symptomatic hypocalcemia was very low (6%); incidence of laboratoristic hypocalcemia was 10%. No permanent hypocalcemia developed. Implementing oral calcium and vitamin D both before and after total thyroidectomy can reduce the incidence of hypocalcemia related to surgery.
Journal of Cellular and Molecular Medicine, 2015
CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms... more CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1.
Journal of endocrinological investigation, 2003
In humans, like as in other mammals, the gonads, the internal genital ducts, and the external gen... more In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for diffe...
Minerva endocrinologica, 2001
Somatostatin (st) exerts a role in the control of prostate growth and function acting both at hyp... more Somatostatin (st) exerts a role in the control of prostate growth and function acting both at hypothalamus-hypophysis level and at glandular level. St analogues have been used to control prostate cancer (CaP) in clinical trials, with contradictory results. These data may be interpreted on the basis of st mechanism of action and tissue distribution of the five st receptors (sst1-5). Sts have been found in prostate tissue and, specifically, in the epithelial component. sst2 is preferentially expressed on normal prostate, sst1 and sst5 on CaP. st inhibits the proliferation of LNCaP and octreotide normal prostate epithelial cells in primary cultures. The lack of sst2 in CaP may explain the ineffectiveness of some selective st analogues in clinical trials. The use of other analogues actually developed with high affinities to ssts expressed mainly in CaP may represent a more rational approach.
Journal of pediatric endocrinology & metabolism : JPEM, 1998
We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudoher... more We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male ps...
Minerva endocrinologica, 1993
The American journal of physiology, 1990
Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid... more Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with an...
Molecular pharmacology, 1992
The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphos... more The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity of membrane preparations by approximately 40%. This inhibition was reversed by atropine, occurred even in a Ca(2+)-free medium containing ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, and was not reproduced by the Ca2+ ionophore A23187. The carbachol effect was not prevented by simultaneous incubation of cells with either isobutylmethylxanthine, an inhibitor of phosphodiesterase, or H-7, an inhibitor of protein kinase. Pretreatment of cells with pertussis toxin to inactivate the Gi inhibitory protein also failed to affect the carbachol inhibition. Although carbachol did not reduce the basal or the TSH-stimulated cyclase activities when ad...
Klinefelter's syndrome (KS) is the most common sex-chromosome male disorder, characterized by one... more Klinefelter's syndrome (KS) is the most common sex-chromosome male disorder, characterized by one or more extra X chromosomes. It is associated with a significant increase of cardiovascular mortality and morbidity. This review examines cardiovascular (CV) abnormalities known in KS until now. KS is associated with both functional and structural CV alterations, particularly KS patients show a wide range of CV abnormalities, specifically LV diastolic dysfunction, impaired exercise performance, Chronotropic Incompetence (CI), and increased carotid intima-media thickness (IMT). Regarding diastolic function, they display an increased Isovolumetric Relaxation Time (IVRT) but no prolongation of Mitral deceleration Time (MdT). This condition indicates the presence of a mild diastolic dysfunction. KS patients also have an exercise intolerance, that depends on reduced stroke volume during exercise, caused by the limited increase in the LV end-diastolic volume despite normal ejection fraction and the increased LV filling pressure and left atrial pressure during exercise. Patients with KS also display a significant increase of carotid IMT, a surrogate marker of atherosclerotic disease. This alteration represents a subclinical marker of early atherosclerosis and is the most important risk factor of new or recurrent stroke and myocardial infarction. Testosterone replacement Klinefelter's syndrome and cardiovascular disease therapy does not normalize the impaired cardiovascular parameters. This wide range of CV abnormalities represents the pathophysiological underpinnings for the raised mortality observed in KS.
Advances in Experimental Medicine and Biology, 1989
Systems Biology in Reproductive Medicine, 1993
Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. ... more Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. This study deals with the sixth recorded family with familial testicular torsion and the effects on the spermatogenesis and the appearance of testicular autoantibodies in three affected subjects (two brothers, aged 18 and 15 years, and their father, aged 48 years). The father and one of the brothers, who had peripubertal unilateral testicular torsion, presented normal fertility and oligozoospermia, respectively. The other brother, who had a history of bilateral testicular torsion, did not present pubertal development until he was 18 years old and he needed substitutive testosterone therapy. Sperm autoantibody titer increased only in the two cases with unilateral torsion and remained unmodified at a 5-year follow-up. The results indicate that testicular torsion can cause variable degrees of spermatogenesis impairment and induce development of autoantibodies against spermatozoa and gonadal antigens. The persistence of fertility in the father and the progressive spermatogenesis recovery in one of the affected sons suggest that the damaging effects of these autoantibodies deserve further investigation.
The Journal of Urology, 1998
Purpose: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group o... more Purpose: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group of cryptorchid boys, and determined whether it may be influenced by orchiopexy.
British Journal of Plastic Surgery, 2003
An increased secretion of cytokines and growth factors has been hypothesised to play a role in th... more An increased secretion of cytokines and growth factors has been hypothesised to play a role in the abnormal growth of keloid fibroblasts. The aim of this study was to evaluate the effect of the calcium antagonist verapamil on the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, as well as on cellular growth, in primary cultures of fibroblasts derived from the central part of keloid lesions. These cells grew faster than peripheral keloid and nonkeloid fibroblasts, and, in long-term cultures, became stratified assuming a three-dimensional structure. Compared with peripheral and nonkeloid fibroblasts, central keloid fibroblasts presented an increased production of both IL-6 and VEGF (P , 0.03 and P , 0.005, respectively). Verapamil (100 mM) decreased IL-6 and VEGF production (P , 0.03 and P , 0.005, respectively) in central keloid fibroblasts cultures at 72 h. Moreover, verapamil decreased cellular proliferation by 29% and increased apoptosis to an absolute value of 8%. The results of this study demonstrate that in primary cultures of central keloid fibroblasts verapamil reduces the sustained basal IL-6 and VEGF production and inhibits cell growth; these data may offer the link with the beneficial effect of calcium antagonists on keloid scars in vivo.
Journal of Molecular Endocrinology, 2000
Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. W... more Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-rastransformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10 7
Journal of Molecular Endocrinology, 2000
To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in ... more To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst 1-5 ) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [ 125 I-Tyr 11 ]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst). The sst 2 transcript was found in nine, sst 3 in five and sst 5 in eight out of ten GO cell cultures. Sst 2 was detected in all six, and sst 3 in four out of the six control cell cultures. Sst 4 was absent from all samples, and sst 1 was found only in six out of the ten GO samples.
Journal of Endocrinological Investigation, 2004
Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medul... more Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism due to specific RET proto-oncogene mutations. Fertile MEN 2A women are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. This condition may cause psychological distress in affected pregnant patients and their families. Here we describe the genetic prenatal testing, the pregnancy management and obstetric outcome in a MEN 2A patient with a right side adrenal hyperplasia and elevated calcitonin levels, a condition suspicious for possible recurrence of pheochromocytoma. We confirm that maternal or fetal complications are rare when MEN 2A diagnosis is made before pregnancy and an accurate monitoring is instituted. Furthermore, our results indicate that prenatal testing for RET mutations is highly recommended in making decisions and assuring parents on the lifelong risk of tumors. This will avoid the psychological distress that can further complicate the pregnancy of affected women.