Biomedical subjects

Alessandro Piovesan

Publications and source records attributed to Alessandro Piovesan.

4 recordsLinked to original sources

PubMed2006

Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor.

INTRODUCTION: Three single-nucleotide polymorphisms in the calcium-sensing receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E have been associated with normal variation in extracellular calcium homeostasis, both individually and in haplotype combination. The aim of this study was to examine haplotype associations in primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Patients with sporadic PHPT (n = 237) were recruited from endocrine clinics and healthy controls (n = 433) from a blood donor clinic, and levels of serum calcium, albumin, and PTH were measured. In PHPT patients, urinary calcium/creatinine clearances and bone mineral density at spine and femoral neck were measured and the presence of kidney stones and vertebral fractures identified. The CASR single-nucleotide polymorphisms were haplotyped by allele-specific sequencing. RESULTS: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight were observed, in keeping with significant linkage disequilibrium, but haplotype frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of 866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect. There was no significant association between haplotype and bone mineral density or fractures, but association with kidney stones was significant (P = 0.0007). In the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95% confidence interval, 1.30-11.3) for presentation with renal stones compared with the rest. CONCLUSION: Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones.

Adult↗

PubMed2006

A slight decrease in renal function further impairs bone mineral density in primary hyperparathyroidism.

BACKGROUND: The impairment of renal function can affect the clinical presentation of primary hyperparathyroidism (PHPT), increasing cardiovascular morbidity, fracture rate, and the risk of mortality. AIM: The aim of the study was to assess the differences in bone status in a series of consecutive patients affected by PHPT without overt renal failure at diagnosis grouped according to creatinine clearance (Ccr). METHODS: A total of 161 consecutive patients with PHPT were studied. They were divided into two groups based on Ccr. Group A had Ccr 70 ml/min or less (n = 49), and group B had Ccr greater than 70 ml/min (n = 112). PTH, total and ionized serum calcium; urinary calcium and phosphate; serum 25-hydroxyvitamin D3; serum and urinary bone markers; lumbar, forearm, and femoral bone mineral density (BMD) were evaluated. RESULTS: Patients in group A were older than those in group B (P < 0.0001). PTH levels did not differ in the two groups, whereas both urinary calcium and phosphorus were lower in group A than group B (P < 0.01). Lower BMD was evident in group A at lumbar spine (P < 0.002), forearm (P < 0.0001), and femur (P < 0.01). In asymptomatic PHPT, those with Ccr 70 ml/min or less had lower forearm BMD than patients with higher Ccr (P < 0.00001). When adjusting for age and body mass index in PHPT, BMD at each site persisted being lower (P < 0.05) in group A than group B. In all PHPT subjects, Ccr (beta = 0.29, P < 0.0005), age (beta = -0.27, P < 0.00001), and PTH levels (beta = -0.27, P < 0.0005) were all independently associated with forearm BMD. CONCLUSIONS: In PHPT a slight decrease in renal function is associated with more severe BMD decrease, independent of age, body mass index, and PTH levels. This association is also present in asymptomatic PHPT and strengthens the National Institutes of Health recommendations for surgery in patients with mild PHPT.

Adult↗

PubMed2005

Unexpected results using rapid intraoperative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism.

Rapid intraoperative parathyroid hormone (RIOPTH) monitoring predicts complete removal of all hypersecreting tissue by means of a significant parathyroid hormone (PTH) decrease. In this study we have tried to provide an explanation for some unexpected results of RIOPTH monitoring observed during a series of 125 conventional parathyroidectomies for primary hyperthyroidism, discussing the possible consequences on the surgical strategy. Three main groups can be recognized: (1) spikes: a PTH increase 10 minutes after removal of the diseased gland was observed in three patients; (2) false-negative results: six patients showed an inadequate PTH decreases at 10 minutes, three of them resulting in cure at 20 minutes (all six patients were cured at follow-up); (3) false-positive results: five patients with multiglandular disease showed a PTH decrease to a cure level despite excision of one adenoma only (in two of these patients a 20-minute sample showed a PTH increase soon after manipulation of the second adenoma). We concluded that the spike, almost certainly a consequence of manipulating the adenoma, when detected should be considered the "true" baseline value. False-negative results are to some extent related to undetected spikes. The assay used for RIOPTH determination and PTH half-life variability may also play a role. A false-negative result usually prolongs the surgical time. False-positive results are usually related to a double adenoma, one functionally prevailing over the other. Because in our experience manipulation of the second adenoma brought a PTH increase detected with RIOPTH monitoring, we believe that the second adenoma should be excised.

Aged↗

PubMed2004

Valproic acid induces the expression of the Na+/I- symporter and iodine uptake in poorly differentiated thyroid cancer cells.

In poorly differentiated thyroid cancer, molecular characteristics are reported to be lost such as to cause insensitivity of the tumor to radiometabolic therapy. Considerable work is in progress to identify compounds that redifferentiate thyroid cancer cells. The present study evaluates the action of valproic acid, a potent anticonvulsant recently reported to inhibit histone deaceytlase, on cultured thyroid cancer cells. N-PA (poorly differentiated) and ARO (anaplastic) cells were treated with increasing valproic acid concentrations.; expression of mRNA and cell localization pattern for the Na+/I- symporter (NIS), as well as 125I uptake, were evaluated before and after treatment. Valproic acid induced NIS gene expression, NIS membrane localization and iodide accumulation in N-PA cells; it was effective at clinically-safe doses in the therapeutic range. In ARO cells, only induction of NIS mRNA was observed, and was not followed by any change in iodide uptake. Valproic acid is thus effective at restoring the ability of N-PA cells to accumulate iodide and its use in clinical trials may be recommended.

Carcinoma↗