Circulating steroid hormones and the risk of prostate cancer.

Epidemiologic studies have failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk and some recent studies have even suggested that high testosterone levels might be protective particularly against aggressive cancer. We tested this hypothesis by measuring total testosterone, androstanediol glucuronide, androstenedione, DHEA sulfate, estradiol, and sex hormone-binding globulin in plasma collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean 8.7 years follow-up and a randomly sampled sub-cohort of 1,859 men. The association between each hormone level and prostate cancer risk was tested using Cox models adjusted for country of birth. The risk of prostate cancer was approximately 30% lower for a doubling of the concentration of estradiol but the evidence was weak (P(trend)=0.07). None of the other hormones was associated with overall prostate cancer (P(trend) >or= 0.3). None of the hormones was associated with nonaggressive prostate cancer (all P(trend) >or= 0.2). The hazard ratio [HR; 95% confidence interval (95% CI)] for aggressive cancer almost halved for a doubling of the concentration of testosterone (HR, 0.55; 95% CI, 0.32-0.95) and androstenedione (HR, 0.51; 95% CI, 0.31-0.83), and was 37% lower for a doubling of the concentration of DHEA sulfate (HR, 0.63; 95% CI, 0.46-0.87). Similar negative but nonsignificant linear trends in risk for aggressive cancer were obtained for free testosterone, estradiol, and sex hormone-binding globulin (P(trend)=0.06, 0.2, and 0.1, respectively). High levels of testosterone and adrenal androgens are thus associated with reduced risk of aggressive prostate cancer but not with nonaggressive disease.     

2D and 3D 3-tesla magnetic resonance imaging of the double bundle structure in anterior cruciate ligament anatomy

For anterior cruciate ligament (ACL) surgery using the anatomic approach of the double bundle concept it is helpful to describe the anteromedial (AM) and posterolateral (PL) bundle using Magnetic Resonance Imaging (MRI), since this is the most important preoperative parameter next to the physical examination. The aim of this study was to distinguish both bundles in MRI. In a prospective study we evaluated the double bundle structure in ACL anatomy with a 3-T ultra-high-field strength MR imaging of cadaver knees, which allows faster imaging times, increased resolution and increased signal-to-noise ratio. Using oblique sagittal and oblique coronal planes, we were able to distinguish the double bundle structure in each knee. The following arthroscopic evaluation of the knees confirmed our MRI findings. Our study demonstrates the possibility of distinguishing the two bundles in the native ACL with 3T MRI. Following examinations must study the value for clinical application by describing different rupture patterns of the bundles and correlating this to arthroscopy. It would be advantageous to know the rupture pattern in advance. Presurgical planning could be improved by reconstructing only the torn and preserving the intact bundle.     

Taxanes from Shells and Leaves of Corylus avellana

Paclitaxel is an effective antineoplastic agent originally extracted in low yield from the bark of Taxus brevifolia. Although it was generally considered a particular metabolite of Taxus sp., paclitaxel was recently found in hazel cell cultures. The aim of the present work was to verify whether hazel differentiated tissues could be used as a commercial source of paclitaxel and other taxanes. Thus, shells and leaves of hazel plants were analyzed by ELISA and HPLC-MS. Both shell and leaf extracts contained taxanes. Among these, paclitaxel, 10-deacetylbaccatin III, baccatin III, paclitaxel C, and 7-epipaclitaxel were identified and quantified. Hazel extracts also showed biological activity, inhibiting metaphase to anaphase transition in a human tumor cell line. The level of total taxanes in leaves was higher than in shells collected in the same period from the same plants. However, the finding of these compounds in shells, which are considered discarded material and are mass produced by many food industries, is of interest for the future availability of paclitaxel and other antineoplastic compounds.     

Managed ventricular pacing vs. conventional dual-chamber pacing for elective replacements: the PreFER MVP study: clinical background, rationale, and design

Aims: Several clinical studies have shown that, in patients with intactatrioventricular (AV) conduction, unnecessary chronic rightventricular (RV) pacing can be detrimental. The managed ventricularpacing (MVP) algorithm is designed to give preference to spontaneousAV conduction, thus minimizing RV pacing. The clinical outcomesof MVP are being studied in several ongoing trials in patientsundergoing a first device implantation, but it is unknown towhat extent MVP is beneficial in patients with a history ofventricular pacing. The purpose of the Prefer for Elective ReplacementMVP (PreFER MVP) study is to assess the superiority of the MVPalgorithm to conventional pacemaker and implantable cardioverter-defibrillatorprogramming in terms of freedom from hospitalization for cardiovascularcauses in a population of patients exposed to long periods ofventricular pacing. Methods and results: PreFER MVP is a prospective, 1:1 parallel, randomized (MVP ON/MVPOFF), single-blinded multi-centre trial. The study populationconsists of patients with more than 40% ventricular pacing documentedwith their previous device. Approximately, 600 patients willbe randomized and followed for at least 24 months. The primaryendpoint comprises cardiovascular hospitalization. Conclusion: The PreFER MVP trial is the first large prospective randomizedclinical trial evaluating the effect of MVP in patients witha history of RV pacing.