Rate of Gleason 7 or higher prostate cancer on repeat biopsy after a diagnosis of atypical small acinar proliferation.

BACKGROUND: Limited information is known about the clinical significance of cancers diagnosed upon repeat biopsy for the indication of atypical small acinar proliferation (ASAP). With increasing concern regarding overdiagnosis and overtreatment of prostate cancer, and the reported rise in infectious complications related to prostate biopsy, we examined the outcomes of patients rebiopsied for a diagnosis of ASAP. METHODS: Clinical, pathologic and outcomes data of patients diagnosed with ASAP on prostate biopsy at our institutions between 2000 and 2010 were abstracted through chart review. Statistical analyses included Fisher's exact and the two-sample Wilcoxon rank sum tests. Logistic regression evaluated risk factors for the probability of cancer following a diagnosis of ASAP. RESULTS: A total of 349 patients met the inclusion criteria with median follow-up of 4.4 years. Median age was 65.3 years with a median PSA of 5.3 ng ml(-1). Of men diagnosed with ASAP, 250/349 (71.6%) had a repeat biopsy within 1 year with 94/246 (38.2%) demonstrating prostate cancer; only 26/245 (10.6%) had ⩾Gleason 7 disease. Of men diagnosed with ASAP, 284/349 (81.4%) underwent biopsy at some time during follow-up. Prostate cancer was diagnosed in 132/279 (47.3%) of these men, 48/278 (17.3%) with ⩾Gleason 7 disease. Multivariate analyses suggested that older age, no previous biopsy and PSA density were predictive of cancer on repeat biopsy within 1 year from ASAP. Univariate analysis revealed PSA density was associated with the presence of ⩾Gleason 7 disease at 1 year and any time after a diagnosis of ASAP. CONCLUSIONS: The overall rate of intermediate- and high-grade prostate cancer found on repeat biopsy for ASAP is low. Further investigation into ways to further risk stratify these men may be warranted. However, until such tests become available, repeat biopsy of men diagnosed with ASAP remains prudent.

Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates.

Although circumcision reduces male acquisition of human immunodeficiency virus type-1 (HIV-1) by 60%, the initial mechanisms of HIV-1 transmission at the foreskin remain elusive. We have established two novel and complementary models of the human adult foreskin epithelium, namely, ex vivo foreskin explants and in vitro reconstructed immunocompetent foreskins. In these models, efficient HIV-1 transmission occurs after 1 h of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs migrate toward the epidermis-dermis interface to form conjugates with T cells, thereby transferring HIV-1. Seminal plasma mixed with cervicovaginal secretions inhibits HIV-1 translocation. This set of results rationalizes at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.

Niche overlap estimates based on quantitative functional traits: a new family of non-parametric indices.

The concept of niche overlap appears in studies of the mechanisms of the maintenance of species diversity, in searches for assembly rules, and in estimation of within-community species redundancy. For plant traits measured on a continuous scale, existing indices are inadequate because they split the scale into a number of categories thus losing information. An index is easy to construct if we assume a normal distribution for each trait within a species, but this assumption is rarely true. We extend and apply an index, NO(K), which is based on kernel density functions, and can therefore work with distributions of any shape without prior assumptions. For cases where the ecologist wishes to downweight traits that are inter-correlated, we offer a variant that does this: NO(Kw). From either of these indices, an index of the mean niche overlap in a community can be calculated: NO(K,community) and NO(Kw,community). For all these indices, the variance can be calculated and formulae for this are given. To give examples of the new indices in use, we apply them to a coastal fish dataset and a sand-dune plant dataset. The former exhibits considerable non-normality, emphasising the need for kernel-based indices. Accordingly, there was a considerable difference in index values, with those for an index based on a normal distribution being significantly higher than those from an index which, being based on kernel fitting, is not biased by an assumption for the distribution. The NO(K) values were ecologically consistent for the fish species concerned, varying from 0.02 to 0.53. The sand-dune plant data also showed a wide range of overlap values. Interestingly, the least overlap was between two graminoids, which would have been placed in the same functional group in the coarse classification often used in functional-type/ecosystem-function work.

Determination of clobazam, N-desmethylclobazam and their hydroxy metabolites in plasma and urine by high-performance liquid chromatography.

Owing to the pharmacological and clinical importance of the determination of plasma and urine levels of the hydroxy metabolites of clobazam and N-desmethylclobazam in healthy volunteers and in epileptic patients, a high-performance liquid chromatographic (HPLC) method was developed that permits the determination of all these compounds in the same plasma or urine sample. The method involved ether extraction at pH 13 with diazepam as internal standard for the measurement of clobazam and N-desmethylcobazam, followed by ether extraction at pH 9 with nitrazepam as internal standard for the measurement of the hydroxy derivatives. The limit of detection was about 10-20 ng/ml for each of these compounds. Applications to patients were limited by chromatographic interferences between the hydroxy metabolites and some medications currently associated with clobazam in the treatment of epilepsy. The only interference in clobazam and N-desmethylclobazam analysis was from N-desmethyldiazepam. Despite these inconveniences, this HPLC procedure appears to be the only available method for the simultaneous quantification of clobazam and its three main metabolites.