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Courtenay K Moore

Publications and source records attributed to Courtenay K Moore.

4 recordsLinked to original sources

The bladder epithelium and overactive bladder: what we know.

Although the urothelium has been traditionally thought of as a passive barrier between urine and detrusor muscle, new studies have shown that the urothelium is a highly specialized structure involved in antigen presentation, micturition reflex, metabolic secretion, inflammatory regulation, and sensory afferent functioning. Data from several laboratories have shown that the urothelium can respond to thermal, mechanical, and chemical stimuli. The earlier findings (activation of urothelial transient receptor potential channel vanilloid 1 producing the second messenger nitric oxide, which in turn triggers suburothelial sensory nerves) demonstrate how the urothelium acts as a transducer, releasing chemicals that target adjacent bladder cells and sensory neurons. We now know that bladder urothelium acts also as a transducer whereby afferent neurons, via urothelial mechanoafferent transduction, are involved in the micturition process and the pathogenesis of bladder disorders. This paper highlights the important role that the urothelium has in bladder pathophysiology.

Humans↗

Role of prostate biopsy schemes in accurate prediction of Gleason scores.

OBJECTIVES: To determine whether improved prostate sampling by the extended biopsy scheme also improves the accuracy of the biopsy Gleason score (bGS). Because most prostate cancer cases are now detected at an early stage with a low prostate-specific antigen level, the bGS may be the most important factor in therapeutic decision-making. Sextant biopsy schemes had poor correlation with prostatectomy Gleason scores. Extended prostate biopsies have replaced the sextant scheme because of the former's greater cancer detection rate. METHODS: We identified 426 patients whose biopsy and prostatectomy specimens were reviewed at our center. To minimize the effect of stage migration, all patients before 1997 were excluded. Of the 426 included patients, 221 men had undergone sextant biopsy and 205 men extended biopsy before prostatectomy. The rate of grading concordance and the effect of different variables on the concordance rate was determined. RESULTS: The overall accuracy of the extended and sextant schemes was 68% and 48% (P <0.001), respectively. Upgrading of the bGS was significantly less likely with the extended scheme (17% versus 41%, P <0.001). The sextant biopsy was more likely to be upgraded for a bGS of 6 or less (44% versus 25%, P <0.002) and a bGS of 7 (14% versus 3%, P <0.02). On multivariate analysis, the biopsy scheme was the only independent predictor of accurate Gleason scoring (P <0.001) and age, prostate-specific antigen level, digital rectal examination findings, prostate size, clinical stage, and number of positive cores were not. CONCLUSIONS: The use of an extended prostate biopsy scheme significantly improves the correlation between the bGS and prostatectomy Gleason score and reduces the risk of upgrading to a worse Gleason group at prostatectomy.

Biopsy↗

Prognostic significance of high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation in the contemporary era.

PURPOSE: High grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in the sextant biopsy had been associated with a high risk of prostate cancer. We determined whether the extended biopsy schemes used in the contemporary era have altered the prognostic value of these lesions at repeat biopsies. MATERIALS AND METHODS: From 1998 to 2003, 105 of 1,188 men had at least 1 repeat extended biopsy due to the presence of HGPIN (33 men) or ASAP (72 men) in a previous extended biopsy. Median biopsy interval for HGPIN and ASAP was 15 and 10 weeks (p <0.05), respectively. Differences in cancer detection rates were analyzed using the Pearson chi-square test. RESULTS: In the HGPIN group only 1 of 22 (4.5%) men had cancer on 1st repeat biopsy and 0 of 11 men had cancer on 2nd repeat biopsy. In men with ASAP 19 of 53 (36%, p <0.005) had cancer on 1st repeat biopsy, and 3 of 19 (16%) had cancer on 2nd repeat biopsy. Cancer was confined to a single core in 16 of 22 (73%) men. Median Gleason score was 6. Patient age, digital rectal examination status, prostate specific antigen, free prostate specific antigen, number of cores and biopsy interval were not independent predictors of cancer in men with ASAP. CONCLUSIONS: HGPIN found in the contemporary extended biopsy does not warrant repeat biopsy. ASAP continues to be associated with a high risk of cancer and requires at least 1 repeat biopsy using the extended biopsy scheme.

Adult↗

Relationship of mass of obstructed rat bladders and responsiveness to adrenergic stimulation.

PURPOSE: The effects of experimental partial bladder outlet obstruction on the bladder response to nerve stimulation and contractile agonists have been well characterized. Mildly obstructed bladders have small increases in mass and increased contractile responses to electrical field stimulation. More severely obstructed bladders become decompensated with large increases in mass and decreased functional responses. Little is known about relaxant mechanisms after obstruction. We investigated the relationship of the increase in rat bladder mass induced by outlet obstruction and responses to alpha and beta-adrenergic stimulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 3 groups, namely control, sham operated and obstructed. Surgical obstruction was done by tying a 2-zero silk ligature around the urethra. The ligature was placed around the urethra and removed in sham operated rats. At 2 and 6 weeks bladders from all groups were harvested, weighed and cut into strips. Contractile responses to electrical field stimulation and norepinephrine in the presence of propranolol were measured. Relaxant responses to norepinephrine and isoproterenol were measured after pre-contraction with KCl. RESULTS: All strips from control and sham operated rats relaxed completely in response to norepinephrine. Obstructed bladders that weighed 2 to 3-fold more than control or sham operated bladders also relaxed. In contrast, bladders that were 5 to 10-fold heavier failed to relax by at least 50% in response to norepinephrine, independent of duration of bladder outlet obstruction. These were called nonresponders. Two week nonresponders relaxed completely in response to isoproterenol, but 6-week nonresponders did not, suggesting that the duration of decompensation is important. All nonresponders relaxed in response to pinacidil (Sigma-Aldrich Corp., St. Louis, Missouri). Nonresponders tended to contract in response to norepinephrine in the presence of propranolol. Strips from the other rats were less responsive, suggesting an increase in alpha1-receptors with decompensation. Contractile responses to field stimulation were increased in obstructed strips that relaxed to norepinephrine, while responses of nonresponders were decreased compared with controls and sham operated rats. CONCLUSIONS: Severely obstructed bladders had an increase in mass and a decreased response to field stimulation, indicative of decompensation. This response was accompanied by decreased ability to relax to beta-agonists and an increased response to alpha-agonists. These changes were not seen in smaller, compensated bladders. Our findings suggest a change in detrusor alpha1 and beta-adrenergic receptor density. An increase in detrusor alpha-receptors may explain the clinical efficacy of alpha-blockers in alleviating irritative voiding symptoms in men with benign prostatic hyperplasia.

Adrenergic Fibers↗