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Biomedical subjects

Alan J Wein

Publications and source records attributed to Alan J Wein.

At least 37 records · Page 2Linked to original sources
PubMed2005

Impact of multiple biopsy cores on predicting final tumor volume in prostate cancer detected by a single microscopic focus of cancer on biopsy.

OBJECTIVES: To compare the impact that the number of biopsy cores have on final pathologic findings when minimal disease is detected at biopsy. Discordance has been noted between transrectal ultrasound-guided biopsy results and tumor volume even when minimal amounts of tumor are found on biopsy. METHODS: We identified patients who had undergone radical retropubic prostatectomy for a single microscopic focus of adenocarcinoma from a prospectively maintained surgical database. Patients were stratified into two groups: those with six biopsies or less and those with seven or more. The Gleason score, margin status, presence of extracapsular extension, and percentage of tumor volume were compared. RESULTS: A total of 102 patients in our database had a single microscopic focus of adenocarcinoma detected by needle biopsy. Of these patients, 65 underwent six or fewer biopsies and 37 underwent seven or more at transrectal ultrasonography. Of the 37 patients in group 2, 27 (73%) had a final tumor volume of less than 5% compared with 24 (37%) of 65 patients in group 1 (P = 0.002). Of the group 2 patients, 15 (75%) with Stage T1c had an estimated tumor volume of less than 5% compared with only 11 (34%) in group 1 (P = 0.01). No statistically significant difference was noted between the two groups for margin status, presence of extracapsular extension, or Gleason score. CONCLUSIONS: A single microscopic focus of cancer obtained after multiple cores predicts for a significantly lower tumor volume on final pathologic examination across clinical stages. In the context of greater tissue sampling, the minimal disease designation may carry more predictive value and be a useful parameter in stratifying patients with Stage T1c and other good-risk factors with regard to surgical outcome.

Adenocarcinoma↗
PubMed2005

Impact of the percentage of positive biopsy cores on the further stratification of primary grade 3 and grade 4 Gleason score 7 tumors in radical prostatectomy patients.

OBJECTIVES: To examine whether the percentage of core biopsies positive can further stratify Gleason score 7 patients with primary Gleason grade into precise prognostic groups. METHODS: Between 1991 and 1999, 379 radical prostatectomy patients were found to have pathologic Gleason 7 tumors. The patients were divided into primary grade 3 or 4. Percentage positive was calculated by dividing the number of positive core biopsies by the total number of cores. RESULTS: In the cohort, 290 tumors were primary grade 3, and 89 were primary grade 4. On univariate analysis patients with primary grade 3 tumors had a significant prostate-specific antigen (PSA) progression-free survival advantage over grade 4 patients. When separated according to percentage of core biopsies positive, statistical analysis revealed significantly better 60-month actuarial PSA progression-free survival for patients with grade 3 and grade 4 and less than 50% core biopsies positive as compared with grade 3 and grade 4 and 50% or more core biopsies positive (85%, 85%, 61%, and 33%, respectively). Furthermore, multivariate analysis demonstrated that primary grade did not have an independent impact on biochemical progression-free survival. However, on subset analysis, among patients with 50% or more biopsy cores positive, primary Gleason grade was indeed found to have a significant, independent impact. CONCLUSIONS: In the present study Gleason 7 patients with primary grade 4 tumors and less than 50% of biopsy cores positive had an excellent prognosis after radical prostatectomy. Our data suggest that among Gleason 7 patients, the percentage of positive biopsies is a stronger predictor of biochemical progression-free survival than primary Gleason grade.

Adult↗
PubMed2005

Mixed incontinence.

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Adrenergic Uptake Inhibitors↗
PubMed2005

Diabetes induced decrease in detrusor smooth muscle force is associated with oxidative stress and overactivity of aldose reductase.

PURPOSE: Bladder dysfunction is one of the complications of diabetes. We determined whether diabetic induced bladder dysfunction is associated with decreased detrusor smooth muscle contractility, hyperglycemia induced over expression of aldose reductase (AR) and increased sorbitol production. In addition, we compared oxidative stress in the detrusor smooth muscle in diabetic rabbits with that in normal rabbits by estimating lipid peroxidation. MATERIALS AND METHODS: Diabetes was induced in New Zealand White, age matched male rabbits by intravenous injection of alloxan (100 mg/kg body weight). Normal and sucrose drinking rabbits served as controls. Six months after the induction of diabetes rabbits with a blood glucose level of 400 mg/dl or higher were sacrificed and detrusor smooth muscle tissue was isolated. Detrusor was analyzed for force generation, lipid peroxidation products using malondialdehyde as a biomarker, and AR expression and function by reverse transcriptase-polymerase chain reaction and sorbitol levels, respectively. RESULTS: The mean maximum force +/- SE produced by detrusor muscle strips in response to 125 mM KCl was 17.50 +/- 1.66, 17.56 +/- 1.23 and 7.51 +/- 2.56 gm/100 mg tissue in normal, sucrose drinking and diabetic rabbits, respectively, representing a 57% force decrease in diabetic subjects. Bethanechol elicited force decreased 40% (26.52 +/- 3.21, 27.3 +/- 2.87 and 16.32 +/- 1.67 gm/100 mg tissue, respectively, in normal, sucrose drinking and diabetic rabbits) in diabetic vs control subjects. Concomitant with the force decrease, the expression of AR, sorbitol content and lipid peroxidation products were increased. CONCLUSIONS: Diabetes induced a decrease in detrusor smooth muscle force. This was associated with an increase in lipid peroxides and sorbitol concomitant with over expression of AR and polyol pathway activation. Our data suggest that these changes might contribute to oxidative stress and decreased contractility of detrusor smooth muscle, leading to bladder dysfunction.

Aldehyde Reductase↗
PubMed2005

Regional alterations in the expression of smooth muscle myosin isoforms in response to partial bladder outlet obstruction.

PURPOSE: Smooth muscle (SM) myosin (SMM) isoform composition is altered in response to partial bladder outlet obstruction (PBOO). A recent study showed that during PBOO the upper dome region of the bladder is subjected to greater expansion pressure than the base and regional differences in contractility exist in the detrusor of PBOO rabbits. We hypothesized that alteration in SMM isoform composition in response to PBOO may show regional heterogeneity. MATERIALS AND METHODS: Detrusor samples were obtained from 9 defined regions of the bladders from dysfunctional PBOO rabbits (greater than 30 voids per 24 hours) and sham operated adult New Zealand White rabbits. Reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to determine the relative levels of SMM isoform expression at the mRNA and protein levels. Contractile responses to bethanechol and KCl were also determined. RESULTS: Myosin isoform expression was uniform throughout the detrusor from sham operated subjects with all regions expressing SM-B almost completely. However, in response to PBOO the dome region showed approximately 70% SM-B and 30% SM-A isoforms, whereas the base region expressed only 35% SM-B and, thus, 65% SM-A. This change also correlated with an approximately 2-fold higher protein level expression of SM-B in the dome region of PBOO rabbit bladders. Expression of the SMemb SMM isoform was significantly increased in PBOO rabbits at the mRNA and protein levels but only in the dome region. Regional differences in SMM isoform expression in the PBOO rabbit bladders correlated with altered contractility. CONCLUSIONS: Alteration in SMM isoform composition in response to PBOO shows regional heterogeneity and may be involved in the mechanism responsible for regional localized differences in detrusor contractility in PBOO rabbits.

Animals↗
PubMed2005

A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis.

PURPOSE: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC). MATERIALS AND METHODS: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively. RESULTS: A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates. CONCLUSIONS: Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.

Administration, Intravesical↗
PubMed2005

Over expression of smooth muscle thin filament associated proteins in the bladder wall of diabetics.

PURPOSE: The thin filament associated proteins caldesmon, tropomyosin and calponin have been shown to modulate actin-myosin interaction, actomyosin adenosine triphosphatase and contraction in smooth muscle. This study was performed to determine whether the expression of these proteins is altered in diabetes induced decrease in the contractility of bladder wall smooth muscle. MATERIALS AND METHODS: Detrusor samples were obtained from New Zealand White male rabbits with alloxan induced diabetes, and from age and sex matched control rabbits. In addition, a bladder myocyte cell line, which continues to express smooth muscle phenotype, was exposed to either normal (5 mM) or high (50 mM) concentrations of glucose. The levels of expression of the thin filament associated proteins were determined at the mRNA and protein levels by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: Detrusor smooth muscle tissue from rabbits with alloxan induced diabetes showed over expression of thin filament associated proteins, calponin, tropomyosin and caldesmon when compared with that of the control. Similar up-regulation was seen also in bladder myocytes in cultures treated with 50 mM glucose, indicating that the high glucose induced the changes. CONCLUSIONS: Our results suggest that the increased expression of thin filament proteins, calponin, tropomyosin and caldesmon in diabetic rabbits might alter the contractile and cytoskeletal structure in bladder myocytes. The over expression of these thin filament associated proteins, which suppresses actin-myosin interaction and actomyosin adenosine triphosphatase, and the enhancement of this suppression by tropomyosin are likely to have an effect on the relationship between force and myosin light chain phosphorylation, requiring higher levels of phosphorylation in diabetic detrusor compared with that of control. The downstream effects of high glucose (eg oxidative stress) appear to modulate the transcriptional regulation of thin filament mediated regulatory proteins in bladder smooth muscle.

Animals↗