PTEN genomic deletion is associated with p‐Akt and AR signalling in poorer outcome,hormone refractory prostate cancer

PTEN haploinsufficiency is common in hormone‐sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non‐metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho‐Akt (p‐Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome was assessed by four‐colour FISH analyses. FISH was performed using six BAC clones spanning both flanking PTEN genomic regions and the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was also evaluated in a subset of cases using single nucleotide polymorphism (SNP) arrays. In addition, the samples were immunostained with antibodies against p‐Akt, p‐mTOR, p‐70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25% showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34% hemizygous deletions only. In a subset of the study group, SNP array analysis confirmed the FISH findings. PTEN genomic deletion was significantly correlated to the expression of downstream p‐Akt (p < 0.0001), AR (p = 0.025), and to cancer‐specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi‐allelic loss correlating to disease‐specific mortality and associated with Akt and AR deregulation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Synchronous intramuscular metastases of malignant melanoma—case report and literature review

Muscular metastasis is a rare event for any malignancy. There are only a limited number of cases reported in the literature in the past. The numbers are even smaller in case of malignant melanoma. We report on an elderly lady with two synchronous skeletal muscle metastases 13 years after initial presentation with malignant melanoma and a brief literature review.     

Systemic hemodynamic changes in mansonic schistosomiasis with portal hypertension treated by azygoportal disconnection and splenectomy

OBJECTIVE: The aim of this study was to assess systemic hemodynamic changes in patients with Manson's schistosomiasis and portal hypertension during azygoportal disconnection and splenectomy. METHODS: Sixteen patients with portal hypertension secondary to hepatosplenic schistosomiasis with indication for surgery were studied prospectively. All underwent invasive hemodynamic monitoring with pulmonary artery catheter. The first systemic hemodynamic assessment was performed preoperatively. In the intraoperative period new hemodynamic data were collected as follows: a) after laparotomy; b) 15-30 min after splenic artery ligature; c) 15-30 min after splenectomy; and d) after ligation of the collateral circulation. RESULTS: The results indicated preoperatively that the patients presented with an increased cardiac index (4.40 +/- 0.94 L/min/m2) together with a reduction in the systemic vascular resistance index (1692.25 +/- 434.91 dyne.s/cm5.m2). The stroke index (53.74 +/- 10.40 ml/beat/m2) and both left (5.71 +/- 1.50 kg.m/m2) and right heart work indexes (1.12 +/- 0.74 kg.m/m2) were also elevated. The mean pulmonary artery pressure was increased (17.81 +/- 9.00 mm Hg) and the pulmonary vascular resistance index decreased (164.31 +/- 138.69 dyne.s/cm5.m2). From the moment that the splenic artery was ligated until the end of the procedure, the cardiac index (3.45 +/- 0.90 L/min/m2) was reduced and the systemic vascular resistance index (2059.50 +/- 590.05 dyne.s/cm5.m5) increased. The systolic index (44.25 +/- 11.01 ml/beat/m2) and the left ventricle work index (4.33 +/- 1.29 kg.m/m2) also reduced. The mean pulmonary artery pressure (19.18 +/- 9.21 mm Hg) and the right ventricle work index (0.94 +/- 0.62 mm Hg) remained elevated after the surgical procedure. CONCLUSIONS: The data allowed us to conclude that hepatosplenic schistosomiasis induces a hyperdynamic circulatory state that was corrected after splenectomy and azygoportal disconnection, remaining a mild pulmonary hypertension. Therefore, these changes are correlated with the portosystemic collateral circulation, especially as a consequence of splanchnic hyperflow.     

Cardiovascular magnetic resonance for suspected cardiac amyloidosis: where are we now?

Heart Failure Reviews - Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality...     

Exploring California’s new law eliminating personal belief exemptions to childhood vaccines and vaccine decision-making among homeschooling mothers in California

Background

California’s Senate Bill 277 (SB-277) law eliminated the personal belief exemption to school immunization requirements. A potential consequence may be that parents choose homeschooling to avoid immunization. Vaccine attitudes and behaviors have not been well studied among the home-schooling population. This study explored the effect of SB-277 and vaccine decision-making among California home schoolers.

Positive sharp waves in the EEG of children and adults

Interictal epileptiform discharges (IEDs) with negative polarity have been extensively studied in the EEG literature. However, little attention has been drawn to IED with positive polarity [positive sharp waves (PSWs)]. In this paper, we discuss pathophysiological, neuroimaging, and clinical correlates of this pattern in a heterogeneous group of children and adults who demonstrated PSW in their scalp EEG. We prospectively reviewed the EEGs of 1,250 patients from a heterogeneous population over a period of 1 year. Thirty-one patients had PSW in their EEG. We documented EEG parameters as well as demographic, clinical, and neuroimaging data. Statistical analysis was performed to correlate the aforementioned data. The analysis showed that PSW is an epileptogenic pattern with localizing significance, occurring primarily in the younger age groups. Furthermore, there was a strong association of PSW with chronic and/or static CNS pathology, in particular, congenital CNS anomalies, often accompanied by psychomotor retardation. Patients with “multifocal’’ PSW invariably exhibited severe intellectual and motor deficits associated consistently with a variety of congenital CNS insults. PSW is a rare and under-reported EEG abnormality which, similar to negative IED, signifies focal epileptogenecity. The presence of PSW should prompt neuroimaging studies to investigate an associated chronic/static CNS pathology, in particular, congenital CNS anomalies. This association is particularly strong when PSW is multifocal in which case patients present with severe intellectual and motor deficits.