Prostate Development in Prune Belly Syndrome (PBS) and Posterior Urethral Valves (PUV): Etiology of PBS-Lower Urinary Tract Obstruction or Primary Mesenchymal Defect?

Prune belly syndrome (PBS) has been recognized since 1950 as the triad of absent abdominal wall musculature, undescended testes, and urinary tract anomalies. The etiology, however, remains uncertain. Theories of mesenchymal maldevelopment, obstruction, and genetic origin have been proposed. To evaluate the role of lower urinary tract obstruction as it relates to prostatic development and PBS, we studied the lower urinary tract of 15 cases of PBS, 8 cases of posterior urethral values (PUV), and 34 age-matched controls. It is generally accepted that prostatic growth and development are dependent on mesenchymal-epithelial interactions. We evaluated the mesenchymal and epithelial differentiation and relationships, and found distinctly different and consistent abnormalities between PBS and PUV as compared with one another and controls. The findings suggest that in PBS, prostatic growth and development are hindered because of destruction or absence of the appropriate primitive mesenchyme. Our studies could not definitely exclude very early obstruction as a cause of the findings because of lack of appropriate fetal material.     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.     

Prime-time television exposure to high priority school-aged social-developmental issues

BACKGROUND: The purpose of this study is to quantify the material children and adolescents are exposed to while watching prime-time television so that school educators, health professionals, and parents can focus on issues of maximum exposure that must be addressed. METHODS: Prime-time programming was recorded from 7 p.m. to 10 p.m. Hawaiian Standard Time daily for 2 weeks in July 2005. Recordings were then viewed to identify social behaviors of interest. RESULTS: Each hour on average, sex was referenced 1.8 times, drugs 0.6 times, tobacco 0.3 times, alcohol 2.4 times, and violence/crime 6.0 times per network. Messages advocating exercise, anti-drug advocacy, and anti-smoking advocacy were each shown 0.2 times per hour; while anti-alcohol advocacy was shown 0.1 times per hour. CONCLUSION: School educators, health professionals, and parents must recognize that prime-time television frequently exposes viewers to issues that are of critical importance to the health and social development of school-aged children and adolescents.     

Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation

Anaplastic large cell lymphoma (ALCL) comprises 10-15% of childhood non-Hodgkin lymphomas (NHL). Systemic ALCL is highly associated with anaplastic lymphoma kinase (ALK) gene translocations with over-expression of ALK protein. We studied ALK rearrangements using fluorescence in situ hybridisation (FISH) and ALK immunohistochemical staining in 43 paediatric systemic ALCLs. FISH (performed on 35 cases) identified a translocation in 29 cases (83%). Immunohistochemistry identified ALK over-expression in 42/43 cases (97%) with the single ALK-negative case demonstrating an ALK rearrangement by FISH, indicating 100% incidence of ALK translocations.     

Rectal hyperreactivity to distention in patients with irritable bowel syndrome: role of distention rate.

BACKGROUND AND AIMS: Rectal motor hyperreactivity to distention may be involved in the pathophysiological course of defecatory symptoms in patients with irritable bowel syndrome (IBS), but results of patient studies are conflicting, possibly because of differences in the applied distention rate. Because a fast rate of distention increases the rectal motor response in healthy subjects, it also may show hyperreactivity in patients with IBS. The aim of this study is to compare the effects of 2 distention rates on rectal motor responses and sensations in 16 patients with IBS and 12 healthy subjects. METHODS: Rectal distensibility and the frequency of rectal contractions and sensations were recorded during volume-controlled rectal distentions at 2 distention rates (10 and 100 mL/min). RESULTS: Recta of patients with IBS were significantly less distensible than those of healthy subjects during fast distention (P = 0.0006), but this difference was not statistically significant during slow distention (P = 0.07). The frequency of rectal contractions and sensations, the majority of which were sensations of gas and a desire to defecate, were significantly greater in patients with IBS during both slow and fast distentions (both P < 0.025). CONCLUSIONS: Recta of patients with IBS are hyperreactive to distention, and fast distention magnifies this abnormal motor response. A greater frequency of sensations during a fixed-time distention period may help to characterize the patients.     

Quality of diabetes care predicts the development of cardiovascular events: results of the QuED study

Background and aimIn the context of the QuED Study we assessed whether a quality of care summary score was able to predict the development of cardiovascular (CV) events in patients with type 2 diabetes.Methods and resultsThe score was calculated using process and intermediate outcome indicators (HbA_1c, blood pressure, low-density lipoprotein cholesterol, microalbuminuria) and ranged from 0 to 40. Overall, 3235 patients were enrolled, of whom 492 developed a CV event after a median follow-up of 5 years. The incidence rate (per 1000 person-years) of CV events was 62.4 in patients with a score ≤10, 54.8 in those with a score between 15 and 20, and 39.8 in those with a score >20. In adjusted multilevel regression models, the risk to develop a CV event was 89% greater in patients with a score of ≤10 (rate ratio [RR] = 1.89; 95% confidence interval [CI] 1.43–2.50) and 43% higher in those with a score between 10 and 20 (RR = 1.43; 95% CI 1.14–1.79), as compared to those with a score >20. A difference between centers of 5 points in the mean quality score was associated with a difference of 16% in CV event risk (RR = 0.84; 95% CI 0.72–0.98).ConclusionOur study documented for the first time a close relationship between a score of quality of diabetes care and long-term outcomes.