Modified Gleason grade of prostatic adenocarcinomas detected in the PLCO cancer screening trial.

PURPOSE: We determined the modified Gleason grade of prostatic adenocarcinomas detected in PLCO to assess grade distribution and compare modified Gleason grades of cancer detected in the intervention arm (organized annual screening) vs the control arm (opportunistic screening). MATERIALS AND METHODS: Modified Gleason grading was performed in 859 radical prostatectomy cases by a single urological pathologist. We compared the proportion of cases with high grade disease in the screened arm vs the control arm by logistic regression analysis. RESULTS: In the intervention arm a modified Gleason score of 5, 6, 7 (3+4), 7 (4+3), 8, 9 and 10 was assigned in 3.6%, 43.3%, 39%, 7.4%, 3.5%, 3.2% and 0.1% of cases, respectively. In the control arm a modified Gleason score of 5, 6, 7 (3+4), 7 (4+3), 8, 9 and 10 was assigned in 3.0%, 35.7%, 46.4%, 7.1%, 5.4%, 1.9% and 0.5% of cases, respectively, after correcting for high grade disease over sampling. A high grade modified Gleason score of 7 or greater was detected in 53% of cases in the intervention arm vs 61.3% in the control arm after correction (p=0.019). The median modified Gleason score was 7 (3+4) in each arm. CONCLUSIONS: A significant percent of cancers in each arm had a component of high grade disease. The modified Gleason grade of prostate cancers detected by organized annual screening was slightly lower than the modified grade of those detected by opportunistic screening. This is an expected consequence of more intensive screening.

Changes in initial expenditures for benign prostatic hyperplasia evaluation in the Medicare population: a comparison to overall Medicare inflation.

PURPOSE: Benign prostatic hyperplasia creates significant expenses for the Medicare program. We determined expenditure trends for benign prostatic hyperplasia evaluative testing after urologist consultation and placed these trends in the context of overall Medicare expenditures. MATERIALS AND METHODS: Using a 5% national sample of Medicare beneficiaries from 2000 to 2007 we developed a cohort of 40,253 with claims for new visits to urologists for diagnoses consistent with symptomatic benign prostatic hyperplasia. We assessed trends in initial inflation and geography adjusted expenditures within 12 months of diagnosis by evaluative test categories derived from the 2003 American Urological Association guideline on the management of benign prostatic hyperplasia. Using governmental reports on Medicare expenditure trends for benign prostatic hyperplasia we compared expenditures to overall and imaging specific Medicare expenditures. Comparisons were assessed by the Z-test and regression analysis for linear trends, as appropriate. RESULTS: Between 2000 and 2007 inflation adjusted total Medicare expenditures per patient for the initial evaluation of patients with benign prostatic hyperplasia seen by urologists increased from $255.44 to $343.98 (p <0.0001). Benign prostatic hyperplasia related imaging increases were significantly less than overall Medicare imaging expenditure increases (55% vs 104%, p <0.001). The increase in per patient expenditures for benign prostatic hyperplasia was significantly lower than the increase in overall Medicare expenditures per enrollee (35% vs 45%, p = 0.0015). CONCLUSIONS: From 2000 to 2007 inflation adjusted expenditures increased for benign prostatic hyperplasia related evaluations. This growth was slower than the overall growth in Medicare expenditures. The increase in BPH related imaging expenditures was restrained compared to that of the Medicare program as a whole.

Production of specific mRNA transcripts, usage of an alternate promoter, and octamer-binding transcription factors influence the surface expression levels of the HIV coreceptor CCR5 on primary T cells.

Surface levels of CCR5 on memory CD4(+) T cells influence HIV-1/AIDS susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA isoforms that differ based on whether they contain or lack the untranslated exon 1. The impact of exon 1-containing transcripts on CCR5 surface expression is unknown. In this study, we show that the increased cell surface expression of CCR5 on primary T cells is associated with selective enrichment of exon 1-containing transcripts. The promoter that drives exon 1-containing transcripts is highly active in primary human T cells but not in transformed T cell lines. The transcription factors Oct-1 and -2 inhibit and enhance, respectively, the expression of exon 1-containing transcripts and CCR5 surface levels. However, polymorphisms at homologous octamer-binding sites in the CCR5 promoter of nonhuman primates abrogate the binding of these transcription factors. These results identify exon 1-containing transcripts, and the cis-trans factors that regulate the expression levels of these mRNA isoforms as key parameters that affect CCR5 surface expression levels, and by extension, susceptibility to HIV/AIDS among humans, and possibly, the observed interspecies differences in susceptibility to lentiviral infection.

Butyl acrylate porous polymer monoliths in fused-silica capillaries for use in capillary electrochromatography.

Capillary electrochromatography incorporates features of both capillary electrophoresis and liquid chromatography. Butyl acrylate polymers, cast in-situ with heat initiated polymerization and no retaining frits have been made. Van Deemter plots of chrysene have been examined at a variety of operating temperatures to examine column behavior. Hmin moves to faster flow-rates and increases slightly in magnitude as temperature is increased. The longevity and reproducibility of the columns have been examined with a homologous series. Performance is very reproducible between two different columns of different diameters, operated on different systems and prepared from the same polymeriation batch. The relative standard deviation of retention factors is a maximum of 3.1% with most values calculated at less than 1%. The uniformity of the polymers as a function of length has also been studied with a series of polycyclic aromatic hydrocarbons, and the columns have proved to be very uniform across their length as measured by the consistency of retention factors with a maximum relative standard deviation of 3.4% and most values calculated between 1 and 2%. Plate numbers of between 65000 and 80000 plates/m have been attained for compounds with retention factors of 3 to 12. These columns have proved easy to make, are quite reproducible, and long lived.