Serologic evidence of human papillomavirus 16 and 18 infections and risk of prostate cancer.

Human papillomavirus (HPV) subtypes 16 and 18 are sexually transmitted and have been associated with an increased incidence of several anogenital tumors. Although previous epidemiological studies have suggested that sexual behaviors such as an early age at first intercourse and larger numbers of sexual partners are also related to an increased risk of prostate cancer, seroepidemiological studies of these infectious agents in relation to prostate cancer have produced differing results. To further evaluate this potential relationship, we completed a population-based control study in King County, Washington. Middle-aged (40-64 years) men diagnosed with prostate cancer (n = 642) were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry between January 1993 and December 1996. Controls (n = 570) of similar age were selected from the same population as the cases by random digit dialing. Overall, there was no association between serological evidence of prior HPV-16 (adjusted odds ratio, 1.06; 95% confidence interval, 0.71-1.57) or HPV-18 (adjusted odds ratio, 1.36; 95% confidence interval, 0.69-2.69) infection and the risk of prostate cancer. Analyses of clinical features demonstrated no relationship between HPV infection status and Gleason score, stage of disease, or a combined measure of disease aggressiveness. Our findings indicate that HPV-16 and HPV-18 are not associated with prostate cancer risk.     

Late results of mitral valve reconstruction in the elderly

BACKGROUND: This study attempts to confirm favorable results with mitral valve reconstruction (MVP) in patients greater than or equal to 70 years of age and to examine complication rates by actual analysis. METHODS: Between June of 1980 and December of 1997, 278 patients 70 years of age or older (mean, 75.2 years; range, 70 to 87 years) underwent MVP for mitral regurgitation. Most involved insertion of an annuloplasty ring. Concomitant procedures were performed in 72.3%, and 55.0% required coronary revascularization. RESULTS: For isolated MVP, the in-hospital mortality rate was 6.5% and 17.0% when combined with coronary revascularization. The mortality rate when combined with another valve procedure was 13.2%. The 5-year freedom from late cardiac death was 100% in the isolated MVP group and 79.7% for MVP with a concomitant procedure (p = 0.006). Complications were analyzed using actual (cumulative incidence) analysis to eliminate the competing risk of noncardiac death. Mean NYHA class improved from 3.32 to 1.71 postoperatively. Repair failure was rare, with a 5-year freedom from reoperation of 91.2%. CONCLUSIONS: These findings confirm the favorable outcome of MVP in elderly patients. Late repair failures are rare; comorbid disease is an important predictor of outcome.     

Mechanical endothelial damage results in basic fibroblast growth factor-mediated activation of extracellular signal-regulated kinases.

BACKGROUND: Endothelial damage, such as that associated with balloon angioplasty or preparation of veins for bypass grafts, results in intimal hyperplasia. Growth factors and cytokines that modulate endothelial cell functions through various intracellular signaling pathways mediate rapid endothelial repair, which may prevent or reduce restenosis. Here we investigated the effect of mechanical injury of endothelial cells on the mitogen-activated kinase signaling pathways, extracellular-signal-regulated kinases (ERKs), C-Jun N-terminal kinase (JNK/SAPK), and p38. METHODS: Confluent human umbilical vein endothelial cells or bovine aortic endothelial cells were wounded with a razor blade; mitogen-activated kinase activation was monitored by immunoblotting with antibodies to active ERK, JNK/SAPK, or p38. RESULTS: Wounding of human umbilical vein endothelial cell or bovine aortic endothelial cell monolayers resulted in rapid (5-minute) activation of ERK-1 and -2, which was abolished by monoclonal antibody to basic fibroblast growth factor (FGF-2). This antibody or an inhibitor of ERK activation, PD98059, also blocked endothelial cell migration after the wounding. Thus FGF-2-induced ERK activation mediates the endothelial response to wounding. CONCLUSIONS: ERK-1 and -2 are activated by FGF-2 released from endothelial cells in response to injury. Therapeutic strategies aimed at reducing FGF-2-induced intimal hyperplasia should preserve ERK activation in endothelial cells while abolishing it in smooth muscle cells.     

A Treatment Model for Craving Identification and Management

Abstract

This article presents an addiction treatment model based on craving identification and management (CIM). Craving is broadly defined as the desire to use alcohol or other drugs; it increases the likelihood of use of these substances. In the CIM Model treatment interventions are referenced to craving, i.e., helping clients to identify their craving level and equipping them with strategies to avoid use. Four causes of craving are identified: (1) environmental cues (triggers): exposure to people, places, and things associated with prior drug-using experiences may cause immediate and overwhelming craving; (2) stress: addicted persons experience stress as craving; (3) mental illness; and (4) drug withdrawal: symptoms of both mental illness and withdrawal lead to craving if clients associate use with relief of these symptoms. The CIM Model incorporates four service delivery elements: Relapse Prevention Workshop, individual counseling, medical/psychiatric services, and screening for ongoing drug use. At its core, the CIM Model asks clients to be aware of craving. analyze its causes, and, based on those causes, implement specific strategies to prevent and manage craving. The CIM Model combines several treatment components. including control of exposure to environmental cues, establishment of a daily schedule, the use of behaviors that dissipate craving (tools), and treatment (with medications when appropriate) of mental health and withdrawal symptoms. The CIM Model is a client-derived approach to achieving and maintaining sobriety based on a process of analyzing craving and managing it with an individualized program of recovery activities.     

Results of randomized controlled trials of low-versus high-osmolality contrast media

The authors reviewed 100 randomized controlled trials (RCTs) conducted in humans to compare safety or efficacy of new low-osmolality contrast media (LOM) with that of high-osmolality contrast media (HOM). Findings of the 43 RCTs judged to be of the highest quality suggest that the efficacy of LOM in imaging is equal or superior to that of HOM for all routes of administration. Heat sensation occurred less often with LOM for all routes and pain occurred less often with LOM for intraarterial routes. No differences were seen in nephrotoxicity or in frequency of nausea, vomiting, urticaria, bronchospasm, laboratory test abnormalities, or neurologic events. Greater cardiovascular changes were seen with HOM, including increased or decreased heart rate, increased left ventricular end-diastolic pressure, decreased systolic pressure, and QT prolongation, depending on route of administration. To demonstrate whether a reduction in clinically significant adverse outcomes truly occurs with LOM, trials will need to enlist larger numbers of patients and employ appropriate outcome measures. Future trials should stratify patients according to their risk of adverse reactions to provide better information about benefits of LOM in low- versus high-risk patients.     

Recently published papers: A series of negative results

Studies with negative results rarely hit the headlines. But the results are often just as important as the positive ones. A number of 'negative headline' studies are looked at in this review: intensive insulin therapy regime, thrombolysis in cardiac arrest, the effects of nutritional guidelines and rapid response outreach teams.     

Bmp15 mutations and ovarian function

BMP15, also known as growth and differentiation factor 9B (GDF9B), is a member of the transforming growth factor beta superfamily (TGFbeta) which in humans, rodents and sheep is expressed exclusively in the oocyte. BMP15 is closely related to GDF9, another oocyte-specific member of this superfamily which has been shown to be essential for early ovarian folliculogenesis. Inactivation of the BMP15 gene in mice has shown only minor effects on fertility. However, Inverdale and Hanna lines of sheep carry naturally occurring mutations in BMP15 which highlight differences in the action of this gene between mice and other mammals. Sheep which are heterozygous show an increase in ovulation rate whereas homozygotes are infertile. The granulosa cell receptor which mediates the BMP15 response has not yet been identified, but the discovery that a point mutation in the BMP1B receptor in Booroola sheep is responsible for increased ovulation rate highlights the importance of the TGFbeta signalling molecules in early folliculogenesis.