Biomedical subjects

Mostafa Elhilali

Publications and source records attributed to Mostafa Elhilali.

At least 19 recordsLinked to original sources

PubMed2006

Effect of the potassium channel opener WAY-133537 on the overactive bladder of spinalized rats.

AIMS: To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were used in this study. Six animals served as normal controls (without spinal cord transaction (ST)), while 42 rats underwent ST at the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was performed in six randomly chosen animals to ensure the development of neurogenic detrusor overactivity. The remaining 36 rats were divided into three equal groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537 0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and treatment group was further divided into two sub-groups (n = 6), with CMG at 3 and 4 weeks after ST, respectively. RESULTS: Two weeks after ST, all "vehicle control" rats developed detrusor overactivity with a mean frequency of 0.96 and 1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2-week treatment, respectively. Neurogenic detrusor overactivity disappeared from 50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor overactivity vanished from 67% of the animals with even further reduction in the frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared from only one animal with a non-significant decline in frequency. Fifty percent of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no detrusor overactivity. CONCLUSIONS: WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.

Animals↗

PubMed2006

Response to daily 10 mg alfuzosin predicts acute urinary retention and benign prostatic hyperplasia related surgery in men with lower urinary tract symptoms.

PURPOSE: We analyzed the influence of treatment response on the risk of acute urinary retention and benign prostatic hyperplasia related surgery in 5,792 men complaining of lower urinary tract symptoms who were treated for 6 months with the selective alpha1-blocker alfuzosin at 10 mg once daily. MATERIALS AND METHODS: The influence of dynamic variables (International Prostate Symptom Score change and bother during treatment) and baseline variables (patient age, prior acute urinary retention managed conservatively, prostate specific antigen, International Prostate Symptom Score and bother severity) on the risk of acute urinary retention and benign prostatic hyperplasia related surgery was estimated using the Kaplan-Meier method and log rank test. The associated HR and 95% CI were calculated using Cox proportional hazard models. RESULTS: During alfuzosin treatment International Prostate Symptom Score improved by 3 or greater and greater than 6 points in 74.8% and 50.3% of men, respectively. In this unselected population, including 3.8% with prior unoperated acute urinary retention, the rate of acute urinary retention and benign prostatic hyperplasia related surgery events during treatment was low (0.5% and 1.1%, respectively). Men with stable or worsening International Prostate Symptom Score were at increased risk for acute urinary retention or surgery (HR 3.75, 95% CI 1.58 to 8.89, p = 0.003 and HR 4.71, 95% CI 2.69 to 8.24, p <0.001, respectively). Prior acute urinary retention was a strong predictor of acute urinary retention relapse and surgery (HR 10.35, 95% CI 4.29 to 26.08, p <0.001 and HR 3.57, 95% CI 1.59 to 7.98, p = 0.002, respectively). Bother score greater than 3 during treatment was the strongest predictor of surgery (HR 7.61, 95% CI 4.16 to 13.93, p <0.001). Prostate specific antigen had much less predictive value. CONCLUSIONS: This 6-month real life practice study shows that alfuzosin is associated with a low incidence of acute urinary retention and benign prostatic hyperplasia related surgery. It also suggests that responder status is the most important predictor of acute urinary retention and benign prostatic hyperplasia related surgery. Thus, first line treatment with alfuzosin may help select patients at risk for benign prostatic hyperplasia progression to optimize treatment.

Acute Disease↗

PubMed2006

Holmium laser enucleation of the prostate in patients on anticoagulant therapy or with bleeding disorders.

PURPOSE: We evaluated the safety and efficacy of HoLEP in patients on anticoagulation with significant obstructive symptoms secondary to BPH refractory to medical therapy. MATERIALS AND METHODS: From May 1999 to October 2004, 83 patients with a mean age of 76.6 years who had symptomatic BPH and were on chronic oral anticoagulant therapy or had bleeding disorders underwent HoLEP. Mean preoperative prostate size estimated by transrectal ultrasound was 82.4 cc (range 25 to 222). A total of 14 patients underwent HoLEP without oral anticoagulant withdrawal, 34 underwent surgery with low molecular weight heparin substitution and 33 stopped anticoagulants before surgery, including 8 on antiplatelet therapy. All patients were assessed preoperatively, and 1, 3, 6 and 12 months after surgery. RESULTS: HoLEP was performed successfully in all patients with a mean enucleation time of 86.5 minutes (range 35 to 210). Mean morcellation time was 20.1 minutes (range 3 to 100). Peak urinary flow, post-void residual urine, International Prostate Symptom Score and quality of life score were significantly improved by 1 month after surgery and they continued to improve during subsequent followup. One patient required intraoperative platelet transfusion and 7 required blood transfusion early in the postoperative period due to hematuria coinciding with restarting oral anticoagulant therapy. Mean preoperative and postoperative hemoglobin was 13.5 (range 8.3 to 16.4) and 12.2 gm/dl (range 5.3 to15.4), respectively (p <0.0001). There were no major operative or postoperative complications, or thromboembolic events. CONCLUSIONS: HoLEP is a safe and effective therapeutic modality in patients on anticoagulation with symptomatic BPH refractory to medical therapy.

Aged↗

PubMed2006

BCG for upper-tract transitional-cell carcinoma: is it safe in patients with renal compromise?

We report three cases of end-stage renal failure necessitating hemodialysis subsequent to BCG administration for the treatment of upper-urinary tract transitional-cell carcinoma in patients with a solitary kidney, one with normal renal function and two with chronic renal failure prior to BCG instillation. We discuss treatment-related issues with pertinent literature review.

Aged↗

PubMed2006

Long-term efficacy and safety of alfuzosin 10 mg once daily: a 2-year experience in 'real-life' practice.

OBJECTIVE: To assess the 2-year efficacy and safety of alfuzosin 10 mg once daily, a selective alpha(1)-adrenoceptor antagonist, in men complaining of lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia (BPH), in 'real life' practice. PATIENTS AND METHODS: In all, 839 European men with LUTS (mean age 67.3 years) were enrolled by general practitioners in a 2-year open-label study with alfuzosin 10 mg once daily. They were asked to complete the International Prostate Symptom Score (IPSS), its appended eighth question (bother score), and the five domains (sexual drive, erection, ejaculation, problem assessment, and overall satisfaction) of the Brief Male Sexual Function Inventory (BSFI). The results were analysed at the endpoint in the intent-to-treat population. RESULTS: At the endpoint the total IPSS improved by 7 points (-38.5%) from baseline (P < 0.001) with 76.9% and 49.7% of men having an improvement of > or = 3 points and >6 points, respectively. There were also significant improvements in nocturia (-0.9, -30%; P < 0.001) and bother score (-1.8, -43%; P < 0.001) from baseline. Most patients (56%) perceived symptom relief within the first 2 weeks of treatment. All BSFI domains significantly improved from baseline (P < 0.05; <0.001 for overall satisfaction) and these improvements were more marked in men with severe LUTS at baseline. Alfuzosin 10 mg was well tolerated; the most common adverse event related to vasodilatation was dizziness/postural dizziness (3.1%). Ejaculatory disorders were uncommon (0.3%). Changes in blood pressure remained marginal, including in elderly men and those receiving antihypertensive agents. CONCLUSIONS: Alfuzosin 10 mg administered for 2 years in real practice is effective in improving LUTS and quality of life, and is well tolerated from a cardiovascular perspective, including in elderly men and those receiving antihypertensive co-medication. Ejaculatory disorders are uncommon. Alfuzosin may even slightly improve various domains of sexual function, such as sexual drive, erection, ejaculation and satisfaction with sexual life.

Adrenergic alpha-Antagonists↗

PubMed2006

The beneficial effect of alfuzosin 10 mg once daily in 'real-life' practice on lower urinary tract symptoms (LUTS), quality of life and sexual dysfunction in men with LUTS and painful ejaculation.

OBJECTIVE: To determine the efficacy and safety of the selective alpha(1)-blocker alfuzosin in men with lower urinary tract symptoms (LUTS) and painful ejaculation, compared with those with LUTS only, as painful ejaculation is one of the most prevalent, differentiating and bothersome symptoms in men with chronic prostatitis/chronic pelvic pain syndrome. PATIENTS AND METHODS: In all, 4857 sexually active men with LUTS had an evaluable answer to the Danish Prostate Symptom Score for Sexual Symptoms question related to pain/discomfort on ejaculation at enrolment in a 6-month open-label study with alfuzosin 10 mg once daily. Efficacy was analysed at the endpoint in the intent-to-treat population. RESULTS: Of the 4857 men, 997 (20.5%) had pain/discomfort on ejaculation and 889/997 (89.2%) considered it was a problem. At inclusion, men with painful ejaculation had more severe LUTS and bother than men with LUTS only. Erectile dysfunction (ED) and reduced ejaculation were more prevalent (74.5% and 71.9%, respectively) and bothersome in men with painful ejaculation than in those with no pain (59.6% and 57.4%, respectively). Under alfuzosin treatment, all variables in both groups significantly improved from baseline; men with painful ejaculation compared to LUTS-only had similar improvements in weighted scores for LUTS (-7.8 vs -7.7), bother (-1.7 vs -1.7), and reduced ejaculate (-0.5 vs -0.4) but greater improvements in ED (-0.6 vs -0.4; P < 0.001). The weighted score for painful ejaculation decreased from 2.2 to 0.8 (P < 0.001). Alfuzosin was well tolerated in both groups. CONCLUSIONS: This 6-month open-label study suggests that alfuzosin 10 mg once daily significantly improves LUTS, quality of life and sexual function in men with prostatitis-like symptoms, and is well tolerated.

Adrenergic alpha-Antagonists↗

PubMed2005

Symptom deterioration during treatment and history of AUR are the strongest predictors for AUR and BPH-related surgery in men with LUTS treated with alfuzosin 10 mg once daily.

OBJECTIVES: To assess the predictors of acute urinary retention (AUR) and/or surgery related to benign prostatic hyperplasia (BPH) in 3514 men complaining of lower urinary tract symptoms and treated for 6 months with the selective alpha1-blocker alfuzosin at 10 mg once daily. METHODS: The impact of baseline (age, prior AUR, prostate-specific antigen tertiles, lower urinary tract symptoms severity, and bother score) and dynamic (International Prostate Symptom Score [IPSS] worsening of 4 points or greater and bother greater than 3 during treatment) variables on the risk of AUR/BPH-related surgery was assessed using Kaplan-Meier curves and log-rank tests. Associated hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. RESULTS: Of the 3514 men analyzed, 140 (4%) experienced a first episode of conservatively managed AUR before inclusion. Of those 140 men, 5 (3.6%) had AUR relapse during alfuzosin treatment and 6 (4.3%) underwent BPH-related surgery. Of those 3374 men without prior AUR, 19 (0.6%) experienced AUR during treatment and 41 (1.2%) underwent BPH-related surgery. During treatment, the most important predictors of AUR were prior AUR (HR 6.35, 95% CI 2.31 to 17.40; P < 0.01), IPSS worsening of 4 or greater (HR 3.34, 95% CI 1.11 to 9.99; P = 0.03), and bother score greater than 3 (HR 3.32, 95% CI 1.29 to 8.53; P < 0.01) at endpoint. Other variables (age, PSA, baseline IPSS, and bother) had much less predictive value. Similar results were observed regarding the risk of AUR and/or BPH-related surgery. CONCLUSIONS: The results of this 6-month real life practice study suggest that prior AUR and symptom deterioration during treatment with alfuzosin 10 mg once-daily (IPSS worsening of 4 or more points, bother score greater than 3) were the strongest predictors of AUR and AUR/BPH-related surgery in men with lower urinary tract symptoms.

Acute Disease↗

PubMed2005

Change in serum prostate specific antigen concentration after holmium laser enucleation of the prostate: a marker for completeness of adenoma resection?

BACKGROUND AND PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a well-established technique for the treatment of benign prostatic hyperplasia (BPH). To date, changes in serum prostate specific antigen (PSA) after HoLEP have not been published. We hypothesized that HoLEP produces a diminution in PSA similar to that produced by the gold-standard therapies for BPH. To test this hypothesis, we have examined PSA data before and after HoLEP from two institutions performing high volumes of this procedure. PATIENTS AND METHODS: Between August 1998 and September 2004, 509 HoLEPs were performed at two institutions for which complete PSA data were available. Preoperative demographic and transrectal ultrasonography (TRUS) volume measurements were recorded; postoperative pathology and TRUS volume were obtained. Change in PSA as a function of the weight of prostate resected and the relation of preoperative TRUS volume to PSA was determined. RESULTS: The average weight of adenoma resected was 49.8 g (range 5-300 g) in the McGill group and 90.4 g (range 7.9-312 g) in the Methodist Hospital group. The mean decrease in PSA was 81.7% in the McGill group (range 6.0-1.1 ng/mL; P < 0.0001) and 86.0% in the Methodist Hospital group (range 8.6-1.2 ng/mL; P < 0.0001). Log transformed preoperative PSA correlated well with TRUS volume (r = 0.45), as did the weight of adenoma resected with absolute change in PSA (r = 0.38). The TRUS volume decreased significantly, from 111.9 cc to 26.5 cc, in the Methodist Hospital group (P < 0.0001). CONCLUSION: The HoLEP procedure produces a significant diminution in PSA that correlates well with the weight of adenoma resected. Measurement of PSA may be a useful tool for the objective assessment of ablative therapies for BPH, as the reduction in PSA corresponds well with the amount of adenoma removed.

Adenoma↗

PubMed2005

Benign prostatic hyperplasia (BPH) and prostatitis: prevalence of painful ejaculation in men with clinical BPH.

OBJECTIVES: To determine the prevalence and importance of pain/discomfort on ejaculation (prostatitis-like symptom) in men with lower urinary tract symptoms (LUTS) diagnosed with clinical benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Baseline data from 5096 men reporting LUTS suggestive of BPH, and enrolled in the ALF-ONE study by general practitioners and urologists in Europe, Asia, Latin America, the Middle East and Canada, were analysed to determine the prevalence and significance of pain/discomfort on ejaculation. All the men were asked to complete the International Prostate Symptom Score (IPSS) questionnaire, the bother score (IPSS question 8), and the Danish Prostate Symptom Score sexual-function questionnaire (DAN-PSSsex) which assesses three symptoms (rigidity of erection, amount of ejaculate and pain/discomfort on ejaculation) and their bothersomeness. RESULTS: There were 3700 sexually active men who had an evaluable answer to the DAN-PSSsex question related to pain/discomfort on ejaculation. Of these, 688 (18.6%) reported pain/discomfort on ejaculation and 609 (88%) considered it was a problem. Patients with painful ejaculation had more severe LUTS and reported greater bother (P < 0.001). Of men with painful ejaculation, 72% reported erectile dysfunction, of whom 91% considered it a problem, and 75% reported reduced ejaculation, of whom 81% considered it a problem. By contrast, of men with no ejaculatory discomfort, 57% reported erectile dysfunction, of whom 79% considered it a problem, and 56% reported reduced ejaculation, of whom 57% considered it a problem. A history of urinary tract infection was reported by 12% of men in the ejaculatory pain group, compared with 7% in the LUTS-only group, while 5% of men in the ejaculatory pain group reported macroscopic haematuria, compared to 3% in the LUTS-only group. Men with ejaculatory pain were slightly younger, but there were no significant differences in duration of LUTS, history of acute urinary retention, prostate-specific antigen concentrations or maximum urinary flow rate compared to the LUTS-only group. CONCLUSIONS: Of sexually active men with LUTS suggestive of BPH, approximately 20% complain of specific prostatitis-like symptoms of pain/discomfort on ejaculation, and these men clearly differ from those who present with LUTS only. For most the symptom is a significant bother. Men with BPH and painful ejaculation have more severe LUTS and reported greater bother, and had a higher prevalence of erectile dysfunction and reduced ejaculation, than men with LUTS only. Evaluation and treatment strategies should address this population of men with symptoms suggestive of both prostatitis and BPH.

Aged↗

PubMed2005

Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction.

OBJECTIVE: To assess the effect on sexual function of alfuzosin 10 mg once daily, a uroselective alpha(1)-blocker, in men with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction. PATIENTS AND METHODS: In all, 3076 men (mean age 65.9 years) were treated for 1 year with alfuzosin 10 mg in 'real life' practice. They were asked to complete the International Prostatic Symptom Score (IPSS), its appended eighth question (bother score) and the Danish Prostatic Symptom Score questionnaire for sexual dysfunction (DAN-PSSsex). The results were analysed at the endpoint in the intent-to-treat population. RESULTS: At baseline, 2434 (79.1%) men were sexually active and answered correctly at least one item of the DAN-PSSsex. Sexual dysfunction was highly prevalent (reduced stiffness of erection, 65.3%; reduced volume of ejaculate, 63.2%; pain/discomfort on ejaculation, 20.2%), and was strongly related to the severity of LUTS and impairment of quality of life. At the endpoint, alfuzosin significantly improved the total IPSS (-6.1, - 32%) and bother score (-1.4, - 33.2%, both P < 0.001) over baseline. In those men with sexual dysfunction there were significant improvements in weighted scores related to reduced rigidity of erection (-0.5), reduced amount of ejaculate (-0.4) and pain/discomfort on ejaculation (-1.2, all P < 0.001) over baseline. The perceived improvements were more marked in men with severe LUTS or a severe bother score at baseline. CONCLUSIONS: Sexual dysfunction is highly prevalent in men with LUTS and related to the baseline IPSS and bother score. Alfuzosin 10 mg once daily for 1 year is effective in improving LUTS and quality of life, and is well tolerated. It may even improve sexual function in those men with concomitant erectile and/or ejaculatory dysfunction.

Adrenergic alpha-Antagonists↗

PubMed2005

Canadian guidelines for the management of benign prostatic hyperplasia.

OBJECTIVE: To develop the first Canadian guidelines for the management of lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH). METHODS: These guidelines, developed under a mandate provided by the Canadian Urological Association (CUA), were a collaborative effort between the CUA guidelines committee and the Canadian Prostate Health Council. BPH guidelines developed by the American Urological Association, the European Association of Urology, the World Health Organization International Consultation on BPH, and similar committees from Germany, Sweden and Australia were reviewed. The committee further reviewed a systematic literature search, updated to May 2004, and systematically derived Canadian urological opinion data. RESULTS: The subsequent Canadian BPH guidelines were developed as an evidence based consensus among the committee members. Mandatory evaluation includes history, physical examination and urinalysis, while a symptom inventory and PSA in selected patients are recommended. Serum creatinine, uroflow, voiding diary, post void residual and sexual function questionnaire are optional. Unless there is an indication, other related tests are not recommended. Treatment choices should be governed by the severity of the symptoms, bother and patient preference. Guidelines for medical, surgical and minimally invasive treatment as well as special considerations are described in terms of guideline, option and recommendation. CONCLUSIONS: Diagnostic and treatment guidelines for BPH reflect the Canadian social priorities, economics, socialized medical practice, manpower issues, and medicolegal considerations.

Canada↗

PubMed2005

Early symptom improvement of benign prostatic hyperplasia (BPH) treated with once daily alfuzosin.

INTRODUCTION AND OBJECTIVES: A novel slow release formulation of alfuzosin should improve compliance by reducing dosing to one 10 mg tablet per day. The current study examined efficacy, at 9 days and 3 months, and safety of this formulation of alfuzosin in BPH patients. METHODS: ALF-X was a 3-month, non-comparative, observational study of 353 BPH patients from 39 Canadian Urology centres. RESULTS: At baseline (BL), mean age was 63.1+/-9.01 years, 92.6% of patients were Caucasian, 3.4% had a history of acute urinary retention, mean duration of the micturition disorder was 48.6+/-54.15 months, and mean PSA was 3.3+/-6.65 ng/mL. Mean total International Prostate Symptom Score (I-PSS) decreased from 17.5 at BL to 10.4 at M3--an improvement of 7.1+/-6.82 points (40.6%, p < 0.001), mostly occurring (27.0%, p < 0.001)) during the first 9 days. Mean Quality of Life Assessment Index improved by 0.7+/-1.39 points between BL and D9 (17.5%, p < 0.001), and by 1.5+/-1.52 points between BL and M3 (37.5%, p < 0.001). The proportion of 'mild' I-PSS patients increased from 11.8% (BL) to 29.7% (D9) to 39.0% (M3); those with 'severe' I-PSS decreased from 37.8% (BL) to 14.5% (D9) to 9.4% (M3). Of 144 patients with nocturia (>2 nightly voidings) at D1, 51.4% improved to < or = 2 nightly voidings at D9, and 60.4% at M3. Adverse events related to alfuzosin occurred in 7.8% of patients; 2.0% experienced serious adverse events. There were no vasodilatory events related to alfuzosin or deaths. CONCLUSIONS: In routine clinical practice, slow-release alfuzosin is associated with a significant improvement in LUTS, and frequency of nocturia, and an excellent safety profile.

Adrenergic alpha-Antagonists↗

PubMed2004

uPM3, a new molecular urine test for the detection of prostate cancer.

OBJECTIVES: To evaluate, in a multicenter study, the diagnostic performance of a new molecular test uPM3 for detecting prostate cancer cells in urine because of the need for better methods to identify patients at risk of prostate cancer. METHODS: The uPM3 test is a nucleic acid amplification assay detecting simultaneously in the urine the relative expression of prostate-specific antigen (PSA) mRNA as a marker of prostate cells and PCA3RNA, which is selectively expressed in most types of prostate cancer. The test is performed using the isothermic nucleic acid-based amplification method, and the two targets are simultaneously detected in real-time fluorescence using specific beacons as probes in a thermostated spectrofluorometer. The test was performed on the first voided urine obtained after careful digital rectal examination of the prostate in men undergoing transrectal ultrasound-guided prostate biopsy. RESULTS: Of 517 patients undergoing biopsy at five centers, 443 (86%) had an assessable sample. Of those, 21%, 55%, and 24% had a total PSA level of less than 4 ng/mL, between 4 and 10 ng/mL, and greater than 10 ng/mL. The corresponding percentage of biopsies positive for cancer in these three groups was 20%, 35%, and 44%. The overall uPM3 sensitivity and specificity was 66% and 89%, respectively. In men with a PSA level less than 4 ng/mL, the sensitivity was 74% and specificity 91%. In those with a PSA level of 4 to 10 ng/mL, the sensitivity was 58% and specificity 91%. In those with a PSA level greater than 10 ng/mL, the sensitivity and specificity was 79% and 80%, respectively. The positive predictive value of uPM3 was 75% compared with 38% for total PSA, and the negative predictive value was 84% compared with 89% and 80% for a PSA cutoff of 2.5 and 4.0 ng/mL, respectively. The overall accuracy was 81% compared with 43% and 47% for total PSA at a cutoff of 2.5 and 4.0 ng/mL, respectively. CONCLUSIONS: These results suggest that the uPM3 molecular urine test may be an important adjunct to current methods for the detection of early prostate cancer.

Adenocarcinoma↗

PubMed2003

Urinary bladder hyperreflexia: a rat animal model.

In this work, we are presenting a rat animal model for bladder hyperreflexia after suprasacral spinal cord transection. Our aim was to standardize an animal model that can be useful in studying this condition. After standardizing the animal model in a pilot study, 26 female Sprague-Dawley rats were subjected to spinal cord transection at the level of T10 vertebra. Four animals were subjected to cystometrogram (CMG) 24 hr after spinalization and six rats 3 weeks post-spinalization. These CMGs were compared to that of six normal controls. The detailed description of the model presented in this manuscript, is the final result after several modifications. All the animals consistently developed hyperreflexia after an initial period of spinal shock phase. Expressed volume of urine continued to decrease until it reached a plateau after peaking at 1-week post-spinalization. The attrition rate reached 27.3% after several improvements in the animal model and was mostly from self-inflicted injuries. Post-operative complications included hypothermia, decubitus ulcers, hematuria, urinary tract infection in addition to the unexplained death of two animals. In conclusion, we believe that this animal model closely resembles the clinical condition of hyperreflexia and follows similar course. The relative low cost of this animal model and the easy maintenance makes it a valuable tool to study such a condition.

Animals↗

PubMed2003

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

OBJECTIVES: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS: After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS: Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.

5-alpha Reductase Inhibitors↗

PubMed2003

Role of 5-HT receptors in treatment of overactive bladder.

Normal bladder function requires coordinated detrusor relaxation and urethral sphincter contraction during the filling phase and the reverse during micturition. This is achieved by the integration of excitatory, inhibitory, and sensory nerve activity in control centers in the spinal cord, pons, and forebrain. It is possible that much of bladder pathology is related to disturbances in the vesical ganglia, sensory reflex loops, and central control of micturition. Experimental studies in animals have revealed that spinal reflex circuits involved in voiding function exhibit a dense serotonergic innervation, multiple 5-HT receptors, and sensitivity to 5-HT receptor agonists and antagonists, and 5-HT reuptake inhibitors. Activity in the serotonergic pathway generally enhances urine storage by facilitating the vesical sympathetic reflex pathway and inhibiting the parasympathetic voiding pathway. Thus, 5-HT receptor antagonists and reuptake inhibitors represent important targets for the development of new treatments of detrusor overactivity and urinary incontinence. Among the drugs modulating the bladder function through 5HT receptor, duloxetine, a potent and selective inhibitor of 5-HT and NE reuptake, is presently undergoing clinical trials for stress urinary incontinence after being shown to be effective in animal models of this condition.

Animals↗

PubMed1999

Learning needs of Canadian urology residents: a survey.

In 1998, we conducted the first national survey of urology residents to evaluate Canadian training programs and other aspects related to the future practice of urology. The survey, a 7-page questionnaire, examined the educational learning needs of the trainees. Of 70 residents surveyed, 41 responded (response rate 60%). Topic areas in which the respondents felt comfortable included uro-oncology, and surgery of the prostate, kidney, and bladder. They were less comfortable with management of incontinence and infertility. In-training evaluation was thought to be an important activity that was well done by the training programs. A large majority (81%) expressed interest in elective rotations which they indicated should last 3 to 4 months. They suggested that research rotations be available, but not mandatory. There was strong support for the concept of a national examination preparation course. Almost half of the respondents indicated that American board examinations in urology were important in that it allowed them a choice between Canada and the United States. These results will be of use to those involved in the training of Canada's future urologists.

Journal Article↗

PubMedDate not supplied

Assessment of cutaneous photosensitivity of TOOKAD (WST09) in preclinical animal models and in patients.

TOOKAD (WST09) is a new, long-wavelength palladium bacteriopheophorbide photosensitizer that targets tissue vasculature. The cutaneous phototoxicity of TOOKAD was assessed in normal rat and pig animal models and in patients in a Phase-I trial of TOOKAD-mediated photodynamic therapy (PDT) for recurrent prostate cancer. Controlled skin exposures were administered using solar-simulated light at various times after drug administration. Two different spectral ranges were used. In the first, the UV portion of the spectrum was removed (UV(-)) because UV irradiation in nondrugged control animals produced an erythema response at incident energy densities (J/cm(2)) lower than those required to induce a PDT response. In the second, the full solar spectrum (UV(+)) was used, and the potentiation by the photosensitizer of the UV-mediated minimum erythema dose was assessed. Results showed that the PDT skin response was negligible at clinical drug doses of 2 mg/kg for any period after administration at light doses of 128 J/cm(2) in the animal models. In patients, there was no observed UV(-) skin response at doses of up to 2 mg/kg, drug-light intervals of 1-3 h or greater and light exposures up to 128 J/cm(2). At higher drug doses in the rat and pig models, the duration of skin phototoxicity was found to be approximately 3 h and less than 1 h, respectively. Using the full spectrum of solar-simulated light, the presence of TOOKAD did not measurably enhance the UV(+)-induced erythema in the rats, pigs or patients.

Animals↗