Biomedical subjects

Alan J Wein

Publications and source records attributed to Alan J Wein.

At least 19 recordsLinked to original sources

PubMed2003

Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.

Partial urinary bladder outlet obstruction (PBOO) in men, secondary to benign prostatic hyperplasia, induces detrusor smooth muscle (DSM) hypertrophy. However, despite DSM hypertrophy, some bladders become severely dysfunctional (decompensated). Using a rabbit model of PBOO, we found that although DSM from sham-operated bladders expressed nearly 100% of both the smooth muscle myosin heavy chain isoform SM-B and essential light chain isoform LC17a, DSM from severely dysfunctional bladders expressed as much as 75% SM-A and 40% LC17b (both associated with decreased maximum velocity of shortening). DSM from dysfunctional bladder also exhibited tonic-type contractions, characterized by slow force generation and high force maintenance. Immunofluorescence microscopy showed that decreased SM-B expression in dysfunctional bladders was not due to generation of a new cell population lacking SM-B. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency correlated with overexpression of SM-A and LC17b. Myosin isoform expression and bladder function returned toward normal upon removal of the obstruction, indicating that the levels of expression of these isoforms are markers of the PBOO-induced dysfunctional bladders.

Animals↗

PubMed2003

Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase.

Detrusor smooth muscle (DSM) undergoes hypertrophy after partial bladder outlet obstruction (PBOO) in male rabbits, as it does in men with PBOO induced by benign prostatic hyperplasia. Despite detrusor hypertrophy, some bladders are severely dysfunctional (decompensated). In this study, the rabbit model for PBOO was used to determine the biochemical regulation of the contractile apparatus and force maintenance by the detrusor from decompensated bladders (DB). Bladders from sham-operated rabbits served as a control. On stimulation with 125 mM KCl, the DSM from sham-operated (SB) rabbits showed phasic contractions, whereas the detrusor from DB was tonic, exhibiting slow development of force, a longer duration of force maintenance, and slow relaxation. The Rho kinase (ROK) inhibitor Y-27632 enhanced the relaxation of precontracted DSM strips from DB. The enhancement of relaxation of the KCl-induced contraction of DB by Y-27632 was associated with dephosphorylation of myosin light chain (MLC20). The DSM extract from DB showed low phosphatase activity compared with that from SB. The DB also showed more Ca2+-independent MLC20 phosphorylation, which was partially inhibited by Y-27632. RT-PCR and Western blotting revealed similar expression levels of MLC kinase and ROK-alpha in SB and DB, but ROK-beta was overexpressed in DB. These results suggest that the ROK-mediated pathway is partly responsible for the high degree of force maintenance and slow relaxation in the detrusor from DB.

Amides↗

PubMed2003

Effect of the Bowman-Birk inhibitor (a soy protein) on in vitro bladder neck/urethral and penile corporal smooth muscle activity.

AIMS: The Bowman-Birk inhibitor (BBI), is a serine protease inhibitor derived from soy beans, which is presently being evaluated in clinical trials for its ability to serve as a cancer preventive or anti-inflammatory agent. The form of BBI currently in clinical trials is known as Bowman-Birk inhibitor concentrate (BBIC). There have been anecdotal reports from patients of improved voiding and sexual functions in the ongoing BBIC trials. The objective of this study was to quantify the effect of BBI and BBIC on urethral and corporal smooth muscle activity. METHODS: In vitro muscle strip studies of New Zealand White rabbit urethra/bladder neck and penile corpora in the presence or absence of BBI or BBIC incubation (5 mg/mL) were performed. RESULTS: In dose-response curves to alpha stimulation, BBI mediated a shift to the right (decreased receptor sensitivity in bladder/urethra as well as corpora with no change in the maximal response). Bladder base/ urethra contraction by field stimulation was significantly inhibited by BBI at higher frequencies (1-32 Hz) (12.2 + 0.8 g vs. 6.3 + 0.75 g, P < 0.05). BBI inhibited field stimulated relaxation of corporal muscle at lower frequencies. Muscarinic contraction of the bladder neck/urethra in alpha prestimulated tissue was significantly inhibited by BBI (5.3 + 0.2 g vs. 2.7 + 0.1 g, P < 0.05). BBI has an inhibitory effect on alpha adrenergic dose-response curves in bladder neck/urethral and corpora smooth muscle. BBI also significantly inhibited neurohumoral cholinergic release and in vitro muscarinic contraction of the urethra. The effects on corpora relaxation were less pronounced. CONCLUSIONS: The data suggest that the phytochemical BBI may promote physiologic effects of urethral relaxation and improved voiding by unique mechanisms and deserves further study as a pharmacologic agent for lower urinary tract symptoms.

Adrenergic alpha-Agonists↗

PubMed2003

An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma.

PURPOSE: The standard of care for muscle invasive transitional cell carcinoma of the bladder is radical cystectomy. Definitive therapy may often be delayed for various reasons. We assessed whether pathological stage and survival correlated with the length of time between diagnosis of muscle invasion and cystectomy. MATERIALS AND METHODS: The records of 290 consecutive patients who underwent radical cystectomy between February 1987 and July 2000 were reviewed. Of 265 (91.4%) cystectomies performed for transitional cell carcinoma data were available for 247 (85.2%) and 189 (65.2%) patients were identified who underwent surgery for muscle invasive disease (T2 or greater). The interval between diagnosis of muscle invasion and cystectomy was calculated for each patient. Patients were divided into groups based on time to surgery as group 1-less than 4 weeks, 2-4 to 6 weeks, 3-7 to 9 weeks, 4-10 to 12 weeks, 5-13 to 16 weeks, and 6-greater than 16 weeks. Exploratory univariate and multivariate analyses were performed to test the association of time lag with clinical features and postoperative survival. RESULTS: Mean patient age was 66 years (range 37 to 84) and overall 3-year Kaplan-Meier estimated survival was 59.1% +/- 4% (median followup 36 months). For all patients mean interval from diagnosis to cystectomy was 7.9 weeks (range 1 to 40). Extravesical disease (P3a or greater) or positive nodes were identified in 84% (16 of 19) of patients when the delay was longer than 12 weeks, compared with 48.2% (82 of 170) in those with a time lag of 12 weeks or less (p < 0.01). Similarly 3-year estimated survival was lower (34.9% +/- 13.5%) for patients with a surgery delay longer than 12 weeks compared to those with a shorter interval 62.1% +/- 4.5% (hazards ratio 2.51, 95% CI 1.30-4.83, p = 0.006). When adjusted for nodal status, and clinical and pathological stages the interval was still statistically significant (adjusted hazards ratio 1.93, 95% CI 0.99-3.76, p = 0.05). CONCLUSIONS: In patients undergoing radical cystectomy a delay in surgery of greater than 12 weeks was associated with advanced pathological stage and decreased survival. Although this relationship persisted after adjusting for nodal status, and clinical and pathological stages, the presence of lymph node metastasis remained the strongest predictor of patient outcome.

Adult↗

PubMed2003

Urologic complications of nonurologic medications.

A physician must be aware of common drug side effects and interactions before prescribing a certain agent. In addition to the drugs that we, as urologists, prescribe, we must also be aware of the urologic side effects of drugs that are commonly prescribed by nonurologists. The mechanisms of the pharmacologic causes for voiding dysfunction, erectile and sexual dysfunction, infertility, and urolithiasis are often mutifactorial and incompletely understood. The recognition and association of a particular drug's potential side effects may save valuable time and money involved in the workup of a patient with a new urologic complaint. It is incumbent on the practicing urologist to be able to recognize the common, and sometimes subtle, urologic complications of medications that are used for nonurologic conditions.

Drug-Related Side Effects and Adverse Reactions↗

PubMed2003

Are urodynamic tests useful tools for the initial conservative management of non-neurogenic urinary incontinence? A review of the literature.

OBJECTIVES: To summarise the evidence for the role of urodynamic tests in the diagnosis and classification of urinary incontinence. METHODS: Reference lists in relevant papers were reviewed and MEDLINE searches conducted. RESULTS: The mean sensitivity (specificity) of clinical history versus urodynamic tests was 0.82 (0.57) for stress incontinence, 0.69 (0.60) for urge incontinence/overactive bladder, and 0.51 (0.66) for patients with mixed incontinence. The proportion of women with a clinical diagnosis of urinary incontinence but with normal findings from urodynamic tests ranged from 3 to 8%. Overall sensitivity of urodynamic tests was about 85-90% in the diagnosis of urodynamic stress incontinence, but generally lower following diagnosis of urge and mixed incontinence. No relationship emerged between urodynamic test results and response to medical treatment. CONCLUSIONS: This literature review shows that the sensitivity of clinical history versus urodynamic tests was 0.82, 0.69 and 0.51 respectively for stress, urge and mixed urinary incontinence. It also suggests that urodynamic diagnosis does not predict response to treatment. These data add to the ongoing 'urodynamics or no urodynamics' debate in the evaluation of urinary incontinence and show that urodynamic testing may not be helpful for patients receiving initial non-invasive therapy. These data are in line with the conclusions of the 1st and 2nd International Consultations on incontinence.

Humans↗

PubMed2003

Evaluation of lower urinary tract symptoms in females.

PURPOSE OF REVIEW: Ongoing controversy exists as to the extent of the necessary evaluation of the female presenting with lower urinary tract symptoms. Most would agree that a detailed history, a physical examination and a urine analysis are essential components of the initial evaluation of lower urinary tract symptoms in the female. Beyond these assessments, however, there are no universally accepted guidelines or recommendations. In selected patients, a urodynamic, endoscopic and/or radiographic evaluation may be indicated. When further investigation of lower urinary tract symptoms is being considered, individual test characteristics, including sensitivity, specificity, reproducibility and accuracy, must be balanced against such factors as cost, morbidity, discomfort, availability and invasiveness. This review discusses some of the recent reports, controversies and developments in the evaluation of lower urinary tract symptoms in the female, and briefly reviews the most recent relevant International Continence Society subcommittee publications. RECENT FINDINGS: The proceedings of the International Consultation on Incontinence, as well as recent publications by a number of its subcommittees, have provided some guidance for the structured evaluation of lower urinary tract symptoms in the female, especially with regard to the investigation of urinary incontinence. The role of urodynamics and radiographic imaging continues to be refined. Magnetic resonance imaging is, at present, still primarily a research tool in the evaluation of lower urinary tract disorders in the female; however, a clinical role for this technology is evolving. SUMMARY: The goal of a diagnostic evaluation is the accurate characterization of lower urinary tract symptoms for the purposes of treatment. Ideally, a brief, low-cost, non-invasive evaluation would provide a high degree of diagnostic accuracy. However, existing technology is limited in this regard. Until future refinements permit a completely non-invasive, cost-effective and accurate analysis of female lower urinary tract symptoms, existing technology must be appropriately utilized. Well-conducted, evidence-based, prospective studies are needed.

Female↗

PubMed2003

Diagnosis and reconstruction of the dorsal or circumferential urethral diverticulum.

PURPOSE: Uncommonly a saddlebag urethral diverticulum (UD) may extend circumferentially around the urethra dorsally or anteriorly with compromise of the adjacent tissues. Excision of the entire mucosalized surface of this type of UD may leave an extensive gap in the urethra. Unfortunately the full extent of a saddlebag UD is often not appreciated on preoperative imaging and it is only discovered intraoperatively when potential reconstructive flaps have already been compromised. The advent of endoluminal magnetic resonance imaging (eMRI) has provided outstanding preoperative staging that has greatly aided in the successful reconstruction of the cases. We present our experience with the diagnosis and reconstruction of these complex UDs. MATERIALS AND METHODS: A review of 41 patients with UD at a single institution revealed 9 with circumferential involvement of the urethra confirmed on eMRI. All patients had voiding cystourethrography as the initial diagnostic modality. Four of the 9 patients had had at least 1 prior attempt at surgical repair elsewhere. Presenting symptoms included severe pain in 7 of the 9 patients, recurrent cystitis in 7, a vaginal mass in 2 and mixed urinary incontinence in 6. Eight of the 9 patients had undergone attempted surgical repair. Surgical reconstruction consisted of complete division of the urethra to access the dorsal wall of the UD with partial urethrectomy. Urethral continuity was restored by end-to-end urethroplasty in 5 patients and by tubularizing the dorsal (anterior) wall of the UD to construct a neourethral segment in 3. A Martius flap and pubovaginal sling were used selectively. Postoperatively voiding cystourethrography was performed in all patients to document absence of the UD. Self-administered patient questionnaires were completed preoperatively and postoperatively. RESULTS: All patients report subjective relief of pain. Six of 8 patients did not use pads for incontinence. One patient used 2 to 3 pads daily for stress urinary incontinence symptoms and 1 had persistent urgency with rare incontinence, for which she used 1 pad daily. Complications included a distal urethrovaginal fistula in 1 patient and urethral stricture in 1. CONCLUSIONS: Circumferential UD is an unusual problem. However, with the use of eMRI as a diagnostic and staging modality the incidence may be higher than previously realized. Preoperative knowledge of the extent of the UD is helpful in ensuring complete excision of the UD and optimizing urethral reconstruction. We conclude that excision and reconstruction of the circumferential UD is possible with excellent symptomatic and anatomical results.

Adult↗

PubMed2003