Mutational analysis of PINX1 in hereditary prostate cancer

BACKGROUND: Telomerase activity is increased in most tumors. PinX1 has recently been identified as a critical component in regulating telomerase activity. The PinX1 gene is located within chromosomal region 8p22-23, a region associated with LOH and potentially linked to increased prostate cancer risk. METHODS: PINX1 was re-sequenced in 159 hereditary prostate cancer (HPC) probands. Four non-synonymous coding variants were genotyped in 159 HPC families. RESULTS: Thirty-nine polymorphisms were identified in the HPC screening panel. Ten coding polymorphisms were identified, seven (Gln50His, Leu91Met, Gln206His, Arg215Ile, Thr220Ala, Ser254Cys, and Glu414Ala) of which were non-synonymous. The most common variants Thr220Ala and Ser254Cys were not significantly over-transmitted from affected parent to affected offspring. CONCLUSIONS: Based on these results, we conclude that PINX1 is not a major factor for HPC risk.     

Reevaluation of the harboe assay as a standardized method of assessment for the hemolytic performance of ventricular assist devices

The Harboe spectrophotometric assay is regarded as one of the safest and most reproducible methods for measuring plasma free hemoglobin (pfHb). However, there is still some ambiguity in the application of the assay when assessing the hemolytic performance of ventricular assist devices (VADs). The purpose of this study was to reexamine and compare values of pfHb obtained using different concentrations of plasma diluent (Na(2) CO(3) ) as cited by various studies such that a standard practice may be recommended for the application of the Harboe assay in the hemolytic evaluation of VADs, allowing reliable comparisons to be made between laboratories. As a means to examine the Harboe assay, a BioMedicus BPX-80 was tested using both whole blood and a washed suspension of red blood cells (RBCs). Results show that for whole blood, the pfHb may be underestimated by 13-23%, dependent upon the concentration of Na(2) CO(3) diluent solution. This trend was not observed for the washed suspension of RBCs. Furthermore, it is shown that the concentration of diluent influences the stability of a sample. The results of this study show that the problems associated with the incongruity of pfHb readings are a direct result of the precipitation of proteins from the plasma under alkaline conditions; as the molarity of the diluent controls pH, it becomes essential to use the appropriate concentration of Na(2) CO(3) diluent in order to avoid turbidity of the solution and the consequent misrepresentation of pfHb values. Such standardization is pertinent when measuring the very low levels of pfHb observed during the in vivo testing of modern ventricular assist devices.     

Automated Assessment of Exclusion Criteria for DXA Lumbar Spine Scans

Modern bone densitometry systems using dual-energy X-ray absorptiometry (DXA) automatically analyze lumbar spine scans and provide clinically important information concerning spine bone mineral density (BMD) and fracture risk. Lumbar spine BMD accurately reflects skeletal health and fracture risk in most cases, but degenerative diseases associated with aging may lead to the formation of reactive bone (osteophytes) and other confounding conditions that elevate BMD without a concomitant increase in bone strength or decrease in fracture risk. Automated densitometry software known as computer-aided densitometry (CAD) (GE Medical Systems Lunar) assists the user in identifying scans with common acquisition and analysis irregularities known to influence BMD values. Visual examination of 231 female spine scans measured with DXA found abnormal conditions that could influence BMD results in 29% of scans. The sensitivity and specificity of several criteria for identifying scans with conditions that could influence BMD were determined. A good criterion for identifying scans with abnormal conditions was a T-score difference of greater than 0.9 or 1.0 between L1-L4 mean and individual vertebrae. Criteria for excluding affected vertebrae were determined. Exclusion of affected vertebrae resulted in a mean BMD decrease of nearly 0.6 SD (T-score) among affected scans.     

Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial.

PURPOSE: The effect of exercise on androgens in middle-aged to older men is poorly understood, and it could have implications for several aspects of health. This analysis was conducted to examine the effects of long-term aerobic exercise on serum sex hormones in middle-aged to older men. METHODS: One hundred two sedentary men, ages 40-75 yr, were randomly assigned to a 12-month exercise intervention or a control group (no change in activity). The combined facility- and home-based exercise program consisted of moderate/vigorous-intensity aerobic activity for 60 min.d(-1), 6 d.wk(-1). Serum concentrations of testosterone, free testosterone, dihydrotestosterone (DHT), 3alpha-androstanediol glucuronide (3alpha-Diol-G), estradiol, free estradiol, and sex hormone-binding globulin (SHBG) were measured at baseline, 3, and 12 months. RESULTS: Exercisers trained a mean of 370 min.wk(-1) (102% of goal), with only two dropouts. Cardiopulmonary fitness (.VO(2max)) increased 10.8% in exercisers and decreased by 1.8% in controls (P < 0.001). DHT increased 14.5% in exercisers versus 1.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P = 0.03). SHBG increased 14.3% in exercisers versus 5.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.9% above baseline in exercisers versus 4.0% in controls (P = 0.13). There were significant trends toward increasing DHT and SHBG, with greater increases in .VO(2max) at 3 and 12 months in exercisers. No statistically significant differences were observed for testosterone, free testosterone, 3alpha-Diol-G, estradiol, or free estradiol in exercisers versus controls. CONCLUSIONS: A year-long, moderate-intensity aerobic exercise program increased DHT and SHBG, but it had no effect on other androgens in middle-aged to older men.     

The impact of surgical excision in chest wall rhabdomyosarcoma: a report from the Children's Oncology Group

Aims

Rhabdomyosarcoma (RMS) is the most common soft tissue tumor of childhood. Patient age, size, histologic finding, and site of the tumor are primary determinants of prognosis in RMS. Chest wall RMS is a site in which the limitations of surgical excision are realized. We aim to determine the impact of surgical excision in chest wall RMS.

Methods

A retrospective chart review was conducted of all 130 pediatric patients enrolled in the Intergroup Rhabdomyosarcoma Study (IRS) with chest wall rhabdomyosarcoma from the first (I) through fourth (IV) IRS with follow-up to June 2005. Median follow-up was 12.1 years (4.6-27.2 years).

Results

There was a significant improvement in failure-free survival (FFS) and overall survival (OS) between the first IRS study, I, and IRS-IV. The estimated FFS and OS at 5 years in IRS I was 30% and 40%, respectively, compared to 68% and 78%, respectively, in IRS-IV (P = .03 and P = .05, respectively). There was no association between histologic finding or size and FFS or OS. However, all patients who presented without metastasis had an FFS and OS of 49% and 61%, respectively, compared with metastatic patients, 7% and 7%, respectively (P < .001). Five-year FFS of group I, II, and III patients was 52%, 52%, and 45%, respectively, and OS was 65%, 60%, and 59%, respectively. There was no significant difference in 5-year FFS or OS in patients who had a complete resection (group I), complete resection with positive microscopic margins (group II), or biopsy or partial resection only (group III). In groups I to III patients, the local and regional failure rate at 5 years is 25% and 6%, respectively.

Conclusions

The most significant impact on outcome in chest wall RMS patients is metastatic disease at diagnosis. The locoregional failure rate is high but does not appear to impact survival. Alternative treatment strategies are needed for chest wall RMS, but aggressive surgical excision may not be necessary.     

Total shoulder arthroplasty

Seventy Neer Series II total shoulder arthroplasties were performed in 65 patients. The average age was 69 years. The average follow-up period was 40 months. Rheumatoid arthritis or osteoarthritis was the diagnosis in 34 and 29 shoulders, respectively. Rotator cuff tears were identified in 18 patients. There were no infections, neurological injuries, or vascular injuries, or vascular injuries. Two glenoid fractures and two humeral shaft fractures were sustained intraoperatively. Uniformly, excellent pain relief was obtained regardless of the disease process. The resultant average increase in range of motion (ROM) was 60 degrees of active forward elevation and 18 degree of external rotation. Radiolucent lines were present in 17 humeral components; however, none was symptomatic or had progressed in thickness. Five glenoid components demonstrated progression of radiolucency, and two required revision. Both of these were in patients with rheumatoid arthritis. Although pain relief was uniformly good among all patient groups, a statistically significant degree of improvement in ROM was found in individuals with osteoarthritis. The etiology of the disease process and the status of the rotator cuff may determine the eventual outcome in individuals treated with total shoulder arthroplasty.