Association between the estrogen receptor beta gene and age of onset of Parkinson's disease

The purpose of this study was to investigate the potential contribution of genetic variants in the estrogen receptor beta gene to the aetiology of Parkinson's disease (PD). Several lines of evidence from human and animal studies suggest a protective role for estrogen in PD. Recently the estrogen receptor beta subtype was reported to be an important mediator of estrogen actions in the nigrostriatal dopamine system. Two single nucleotide polymorphisms at position 1730 and 1082 in the ER beta gene were genotyped, using pyrosequencing, in 260 patients with PD and 308 controls recruited from the Swedish population. Neither of the two estrogen receptor beta polymorphisms was associated with an increased risk for PD. However, the G allele of the A1730G polymorphism was more frequent in patients with an early age of onset than in patients with a late age of onset of PD (P = 0.006). Patients carrying the GG genotype had an odds ratio of 2.2 for having an early onset of PD compared to non-carriers. In conclusion, our results indicate that genetic variation in the estrogen receptor beta gene may influence the age of onset of PD.     

In vitro platelet aggregation defects in patients with myeloproliferative disorders and high platelet counts: Are they laboratory artefacts?

It has been recently shown that in vitro platelet aggregation is inhibited when platelet concentration in platelet-rich plasma (PRP) is “normalized” by the addition of platelet-poor plasma (PPP). In this study we tested the hypothesis that the large amount of PPP required to “normalize” PRP in patients with thrombocytosis may result in falsely defective platelet function. To this end, we evaluated platelet aggregation in PRP samples “normalized” with either PPP or buffer in 16 patients with high platelet counts induced by myeloproliferative disorders. Comparison with the results obtained in healthy subjects demonstrated that patients had reduced platelet responses to ADP or collagen in PRP/PPP samples, but normal responses in PRP/buffer. By contrast, the majority of patients had severely defective platelet response to epinephrine independently from the methodological approach. We suggest that the reduced in vitro platelet aggregation previously described in patients with myeloproliferative disorders and thrombocytosis partially derived from a laboratory artefact.     

Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension

This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units (Mid-South of Italy), and in 100 healthy Caucasian subjects randomly recruited from the same area. Cardiac anatomy and function were analysed by non invasive diagnostic imaging techniques (Echocardiography standard m-mode, 2D, colour-Doppler) and by invasive studies (cardiac catheterization). Molecular screening of the region of interest was performed by automated sequencing. At univariate analysis, patients with the His323His TT genotype show a lower cardiac index (2 ± 0.6 vs. 2.3 ± 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 ± 9.6 vs. 14.2 ± 6.9; p = 0.01) at cardiac catheterization. A logistic multivariate model shows idiopathic disease (p = 0.01; OR = 3.8; CI = 1.3-11) and indexed pulmonary vascular resistances (p = 0.01; OR = 1.1; CI = 1-1.2) as independent predictors of TT genotype. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH.     

Prognosis of patients with spontaneous rupture of hepatocellular carcinoma in cirrhosis

The treatment of cirrhotic patients with spontaneous rupture of hepatocellular carcinoma (HCC) is controversial and largely dependent on general conditions of the patients and compensation of the underlying cirrhosis. We retrospectively reviewed clinical, imaging and surgical records of 24 consecutive cirrhotic patients (17 males, 7 females; age range 52–88 years) with hemoperitoneum from spontaneous rupture of HCC observed from June 2004 to January 2010 at our Institution. When indicated, patients were referred to surgery or trans-arterial embolization (TAE). Advanced decompensated patients were conservatively treated and clinically followed up. Spontaneous rupture of HCC was assessed by aspiration of bloody ascites at paracentesis in all cases. The presence of large blood-clots over HCC and liver surface at US and/or CT was considered a specific sign of ruptured HCC in 14 cases. In two out of four patients who underwent TAE active bleeding from tumor surface could be demonstrated. In 2 cases, the active hemorrhage from the HCC surface could be assessed by contrast-enhanced ultrasonography. Four out of 24 patients underwent surgery. Three out of four of these patients died within 2 weeks, 8 months, and 20 months after operation, respectively. The remaining patient is still alive at 52 months follow-up. Four patients underwent TAE and died at 1, 2, 6 and 10 months after treatment, because of recurrent peritoneal bleeding and/or liver failure. Sixteen patients with ruptured HCC in the advanced Child C cirrhosis were treated conservatively with blood derivative transfusion and with procoagulant drugs. All patients, but one died within 2–18 days. One patient survived the acute hemorrhage from ruptured HCC and died of liver failure after 3 months. We concluded that spontaneous rupture of HCC is usually a fatal event in patients with poor liver function, even after successful TAE. In compensated patients, timely surgical treatment can result in long term and even tumor-free survival of the patient.     

Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Neuropathy and peripheral artery disease represent the main pathophysiological conditions underlying diabetic foot. Several studies showed that Lipoprotein(a)-Lp(a)-and homocysteine (Hcy) can be associated with diabetic complications, but their relationship with diabetic foot is unclear. Aim of this study was to investigate whether Lp(a) and Hcy were associated with diabetic foot ulcerations, classified according to the presence of peripheral artery disease (PAD) or neuropathy. From among consecutive type 2 diabetic attending at the Diabetic Foot Clinic 27 subjects with vascular diabetic foot (VDF), 43 with neuropathic diabetic foot (NDF) and 52 controls without foot ulceration, neuropathy, and PAD were enrolled. Both Lp(a) (26.1 ± 22.7 vs. 14.9 ± 19.5 mg/dl; P = 0.003) and Hcy levels (15.4 ± 5.7 vs. 12.2 ± 5.1 μmol/l; P = 0.022) were significantly greater in the VDF group than in controls. Lp(a) levels were significantly lower in the NDF group than in controls (6.9 ± 8.1 versus 14.9 ± 19.5 mg/dl; P = 0.009), while no difference in Hcy levels was found. Multiple logistic regression analysis showed that Hcy was associated with VDF (OR: 1.11; 95% CI: 1.07-14.1; P = 0.048). Lp(a) did not enter the model, but its P-value was very near to the significant level (OR: 1.09; 95% CI: 0.99-12.05; P = 0.059). Moreover, low Lp(a) levels were associated with NDF (OR: 0.84; 95% CI: 0.21-0.96; P = 0.039). Our study has shown for the first time that high Lp(a) and Hcy levels are associated with the development of VDF, while low Lp(a) levels appear to be associated with delayed wound healing in patients with neuropathic foot ulcerations.     

Changes in left anterior descending coronary artery wall thickness detected by high resolution transthoracic echocardiography

Recently, it has been demonstrated that high-resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. The aim of this study was to further validate this technique. One hundred ten volunteers, 58 patients with angiographically proved CAD and 52 control subjects, underwent assessments of their LADs using HRTTE. Anterior and posterior wall thicknesses differed between subjects in the CAD group and controls (1.9 +/- 0.6 vs 1.2 +/- 0.3 mm, p <0.001, and 1.8 +/- 0.5 vs 1.2 +/- 0.3 mm, p <0.001, respectively). External LAD diameter was also greater in subjects in the CAD group compared with controls (5.2 +/- 1.9 vs 4.4 +/- 0.9 mm, respectively, p = 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and the controls (1.9 +/- 0.9 vs 2.1 +/- 0.8 mm, respectively, p = 0.3). In conclusion, HRTTE demonstrated that LAD wall thicknesses and external diameters in patients with CAD were significantly larger than in normal volunteers. Luminal diameter, however, was maintained in the 2 groups, indicating that subjects in the CAD group had undergone positive remodeling at the site measured. This objectively visualized evidence of coronary atherosclerosis with HRTTE would likely be undetected during coronary angiography.