Germline mutations in the von Hippel–Lindau gene in Italian patients

von Hippel–Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumours, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumours.The current study investigated the occurrence of VHL mutations in Italian patients with classic VHL disease or with atypical VHL-like clinical features referred to the Service of Medical Genetics for VHL molecular diagnosis. In addition, an RQ-PCR protocol was validated in order to introduce it in the routine VHL laboratory diagnosis.     

Microvascular reconstruction of the columella using a small radial forearm free flap: a case report

Columellar defects can result from various causes, a number of methods have been described for the reconstruction using local, regional, or free flaps. When local tissues are not available due to the presence of scars, free flaps become the treatment of choice. We present the case of a columellar defect resulting from a distal necrosis of a forehead flap in total nasal reconstruction. The columella was reconstructed using a small radial forearm free flap and a conchal cartilage graft. The flap and the graft survived completely with a satisfactory cosmetic result and good respiratory function during the follow-up time of 2 years. The result was achieved in a single-stage operation: the patient did not need any further procedures to improve the nasal appearance. We propose that the radial forearm free flap may be an easy and reliable alternative among the surgical options for columellar defects when local tissues are not available.     

Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy

In this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid -AA- and 2 and 10 microM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents - group A- and 167 on dual antiplatelet agents plus GpIIb/IIIa inhibitors - group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p = 0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p < 0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p < 0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p < 0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both group A and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA, ADP 2 microM-PA and ADP 10 microM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.     

Reflux symptoms in professional opera choristers

BACKGROUND AND AIMS: A specific, occupation-related susceptibility of professional singers to experience gastroesophageal reflux was hypothesized. We investigated the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers in comparison with a general population sample. METHODS: A total of 351 professional opera choristers from well-known chorus in different Italian regions were identified and a sample of 578 subjects residing in the same areas with a similar distribution in age and sex was selected. Reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits were investigated in both study groups through a structured questionnaire. Prevalence rate ratios, adjusted for sex, age, body mass index, smoking status, alcohol consumption, and other confounding factors, were computed. RESULTS: Opera choristers reported a statistically significant higher prevalence of heartburn, regurgitation, cough, and hoarse voice than the population sample, with adjusted prevalent rate ratios of 1.60 (95% confidence interval [CI], 1.32-1.94), 1.81 (95% CI, 1.42-2.30), 1.40 (95% CI, 1.18-1.67), and 2.45 (95% CI, 1.97-3.04), respectively. Regurgitation appeared to be associated consistently with the cumulative lifetime duration of singing activity (P = .04) and with the weekly duration of singing activity (P = .005) when different multivariate models were applied. CONCLUSIONS: Opera choristers reported a higher prevalence of reflux symptoms than the population sample. Future studies will be needed to clarify whether gastroesophageal reflux in professional opera choristers is stress-induced and therefore may be considered as a work-related disease.     

Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer

Total thyroidectomy and central neck dissection are the procedures of choice in patients affected with medullary thyroid cancer. It is known that a medullary thyroid cancer with node metastases can be rarely cured, and therefore the utility of a modified radical neck dissection in the absence of suspicious node metastases still needs further evidence. The study aims to verify whether other epidemiological and pathological parameters could affect the prognosis of medullary thyroid cancer patients. We prospectively studied 70 medullary thyroid cancer patients consecutively operated on (from 2000 to 2004) at the same institution and analysed by the same pathologists. All patients underwent total thyroidectomy and central lymphadenectomy. In 27 cases, the ipsilateral (n=19) or bilateral (n=8) modified radical neck dissection was performed in the presence of suspicious lateral neck node metastases. After surgical treatment, basal and stimulated serum calcitonins (Cts) were measured in all patients. Follow-up ranged between 1 and 4 years. Patients were considered 'cured' when stimulated Ct was undetectable. Age, sex, tumour size, tumour capsule, multicentricity, nodes in the central neck and mean number of positive nodes were analysed in 'cured' and 'not-cured' patients. The presence of node metastases in the central compartment was significantly correlated with the outcome of the patients, being present in 9 and 72% of cured and not-cured patients respectively (P<0.000001). Tumour size was also significantly correlated with the outcome of the disease (P<0.00006). The presence of the tumour capsule correlated with better prognosis (P=0.0005) and absence of node metastases (P=0.0080). By multivariate analysis, the presence of node metastasis remained the most significant variable affecting the outcome of the disease (P=0.000014). Our results show that the outcome of encapsulated cancer is significantly better regardless of tumour size and node metastases. Although the early diagnosis and the extensive surgical treatment may favour the good outcome of medullary thyroid cancer, they do not always guarantee the definitive cure of the disease, being the capsular infiltration an independent bad prognostic factor.     

The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration

Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Galphai) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5'-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase-activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Galphai proteins and RhoGTPases.     

Treatment of pilonidal sinus with primary closure. A twenty-year experience

From 1985 to 2004, 229 patients (171 M, 58 F) aged from 16 to 35 years, affected by pilonidal sinus were treated by complete excision of the sinus and primary closure. Primary healing was achieved in 208 patients (91%) in an average time of 11.9 days. Secondary healing was achieved in 21 patients (9%) in 16-19 days. The mean postoperative hospital stay was 1.9 days and the average time off work 16 days. Recurrent pilonidal sinus was observed in 10 patients with a mean follow-up of 18 months (range: 12-24). On the basis of their experience, the authors conclude that complete excision of the pilonidal sinus with primary closure yields good results in terms of healing, morbidity, early return to work and recurrence rate and can be considered the treatment of choice for pilonidal sinus.