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Biomedical subjects

M Elhilali

Publications and source records attributed to M Elhilali.

At least 19 recordsLinked to original sources

Age, comorbidity and hypertensive co-medication do not affect cardiovascular tolerability of 10 mg alfuzosin once daily.

PURPOSE: We assessed in real-life practice the impact of age, cardiovascular comorbidity and co-medication on the tolerability and efficacy of 10 mg alfuzosin OD in men with lower urinary tract symptoms suggestive of benign prostatic obstruction. MATERIALS AND METHODS: A total of 6,523 men with a mean age of 64.7 years were enrolled in a 6-month open label study of 10 mg alfuzosin OD. They were stratified by age quartile (younger than 60, 60 to 64, 65 to 70 and older than 70 years), comorbidity (hypertension, ischemic heart disease and diabetes) and antihypertensive co-medication (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II inhibitors and calcium channel antagonists). RESULTS: Alfuzosin was effective and well tolerated. Despite an increased prevalence of cardiovascular comorbidity and antihypertensive co-medication with age changes in blood pressure did not significantly differ among age groups. In controls, ie those with no cardiovascular comorbidity or co-medication, alfuzosin produced minimal decreases in sitting systolic (mean -2.6 to -2.8 mm Hg) and diastolic (mean -1.7 to -1.8 mm Hg) blood pressure. In men with cardiovascular comorbidity mean decreases in systolic (-3.5 to 5.8 mm Hg) and diastolic (-2.0 to -3.3 mm Hg) blood pressure remained marginal. Of the 6,523 exposed patients 19.3% withdrew from the study, mainly for adverse events (6.4%) or a lack of efficacy (5.3%), while 229 (3.5%) experienced serious adverse events and 1,558 (23.9%) reported at least 1 treatment emergent adverse event. The most commonly reported adverse event was dizziness/postural dizziness (4.8%). Hypotension/postural hypotension was uncommon (0.7%). Age, cardiovascular comorbidity and antihypertensive co-medication had no impact on the safety profile of 10 mg alfuzosin OD. CONCLUSIONS: Alfuzosin (10 mg) OD is effective and well tolerated, and it has marginal effects on blood pressure, including in elderly patients and those with hypertension, ischemic heart disease or diabetes and those receiving antihypertensive agents.

Adrenergic alpha-Antagonists↗

Murine renal cell carcinoma: evaluation of a dendritic-cell tumour vaccine.

OBJECTIVE: To use a murine model of renal cell carcinoma (RCC), Renca, to aid in developing a dendritic cell (DC)-mediated tumour vaccine for RCC; as conventional therapy has been unsuccessful for RCC and therapy using immune modulators has had limited success, novel therapies enhancing further the immune system must be developed. MATERIALS AND METHODS: DCs were obtained from mouse bone marrow enriched for the haematopoietic progenitors, and cultured in the presence of interleukin-4 and granulocyte macrophage-colony stimulating factor. In vivo vaccines and in vitro proliferation assays were used to assess ability of the DCs to present tumour antigen. RESULTS: The presence of DCs was confirmed in the cultures by fluorescent-activated cell sorting analysis. In vivo, tumour-bearing animals receiving tumour extract-pulsed DCs as a vaccine showed a two to threefold reduction in tumour growth at day 12 and day 16 but no significant difference at day 28. In vitro, tumour extract-pulsed DCs stimulated significant proliferation of splenocytes from naive animals but not tumour-bearing animals. In addition, splenocytes from tumour-bearing animals had an attenuated immune response in vitro. CONCLUSION: These results show that it is possible to use the DC vaccine to modulate the immune response to achieve an antitumour effect, but further manipulation of the DC vaccine may be needed to overcome the tumour-induced immune suppression.

Animals↗

The clinical burden of prostate cancer in Canada: forecasts from the Montreal Prostate Cancer Model.

OBJECTIVES: The incidence of prostate cancer is increasing, as is the number of diagnostic and therapeutic interventions to manage this disease. We developed a Markov state-transition model--the Montreal Prostate Cancer Model--for improved forecasting of the health care requirements and outcomes associated with prostate cancer. We then validated the model by comparing its forecasted outcomes with published observations for various cohorts of men. METHODS: We combined aggregate data on the age-specific incidence of prostate cancer, the distribution of diagnosed tumours according to patient age, clinical stage and tumour grade, initial treatment, treatment complications, and progression rates to metastatic disease and death. Five treatments were considered: prostatectomy, radiation therapy, hormonal therapies, combination therapies and watchful waiting. The resulting model was used to calculate age-, stage-, grade- and treatment-specific clinical outcomes such as expected age at prostate cancer diagnosis and death, and metastasis-free, disease-specific and overall survival. RESULTS: We compared the model's forecasts with available cohort data from the Surveillance, Epidemiology and End Results (SEER) Program, based on over 59,000 cases of localized prostate cancer. Among the SEER cases, the 10-year disease-specific survival rates following prostatectomy for tumour grades 1, 2 and 3 were 98%, 91% and 76% respectively, as compared with the model's estimates of 96%, 92% and 84%. We also compared the model's forecasts with the grade-specific survival among patients from the Connecticut Tumor Registry (CTR). The 10-year disease-specific survival among the CTR cases for grades 1, 2 and 3 were 91%, 76% and 54%, as compared with the model's estimates of 91%, 73% and 37%. INTERPRETATION: The Montreal Prostate Cancer Model can be used to support health policy decision-making for the management of prostate cancer. The model can also be used to forecast clinical outcomes for individual men who have prostate cancer or are at risk of the disease.

Adult↗

The economic burden of prostate cancer in Canada: forecasts from the Montreal Prostate Cancer Model.

BACKGROUND: We developed an economic model of prostate cancer management from diagnosis until death. We have used the Montreal Prostate Cancer Model to estimate the total economic burden of the disease in a cohort of Canadian men. METHODS: Using this Markov state-transition simulation model, we estimated the probability of prostate cancer, annual prostate cancer progression rates and associated direct medical costs according to patient age, tumour stage and grade, and treatment modalities in a 1997 cohort of Canadian men. The estimated lifetime costs of prostate cancer included the costs of clinical staging, initial treatments and complications, follow-up cancer therapies, routine outpatient care, and palliative care following metastatic disease. RESULTS: The clinical burden of prostate cancer forecasted using the model was similar to the projections of the National Cancer Institute. In the 1997 cohort of 5.8 million Canadian men between 40 and 80 years old, prostate cancer would be diagnosed in an estimated 701,491 men (12.1%) over their lifetime. Direct medical costs would total $9.76 billion, or $3.89 billion when discounted 5% annually. INTERPRETATION: The Montreal Prostate Cancer Model indicates that the economic burden of prostate cancer to Canada's health care system will be substantial. Further analyses are needed to identify the most efficient means of treating this disease.

Adult↗

Practice patterns of Canadian urologists in benign prostatic hyperplasia and prostate cancer. Canadian Prostate Health Council.

PURPOSE: We reviewed the practice patterns of Canadian urologists in benign prostatic hyperplasia (BPH) and prostate cancer, and assessed the changes that occurred between 1995 and 1998. MATERIALS AND METHODS: In 1995 and 1998 questionnaires were mailed to all active members of the Canadian Urological Association who practiced adult urology in Canada. Many questions were similar, allowing for the assessment of changes in practice patterns. RESULTS: A number of changes were observed between 1995 and 1998. Cystoscopy and imaging of the upper urinary tract were used less often to evaluate uncomplicated cases of BPH. However, 39% of respondents continued to perform cystoscopy routinely. Finasteride was no longer administered in men with a smaller prostate. In 1998 before radical prostatectomy 28% of respondents routinely performed a bone scan, 29% cystoscopy and 57% chest x-ray. The number believing that maximal androgen blockade is the most effective hormonal therapy decreased from 90% to 62%, while 24% reported in the 1998 survey that they frequently administered intermittent hormonal therapy. Comparison with an American study from 1995 indicated that American urologists used the American Urological Association symptom score and performed a prostate specific antigen test more frequently than Canadian urologists. However, Canadian urologists performed cystoscopy more frequently. CONCLUSIONS: These surveys provide a useful insight into the variations in clinical practice of Canadian urologists and help to determine whether changes are occurring in regard to the development of practice guidelines. They also indicate the need to develop further guidelines, and ensure that these guidelines are widely promoted and accepted by the urological community.

Adult↗

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

OBJECTIVES: The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years. RESULTS: Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of -24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the quasi-American Urological Association symptom score was decreased by 4.3 points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average. Finasteride was well tolerated, with no significant increase in the prevalence of sexual adverse events over time. CONCLUSIONS: Patients treated with finasteride 5 mg maintained an initial decrease in prostate volume and improvement in symptom score and maximal urinary flow rate over 5 years.

Double-Blind Method↗

Impact of a shared decision-making program on patients with benign prostatic hyperplasia.

OBJECTIVES: To determine patient views about the Shared Decision-Making Program (SDP), an interactive videodisk program designed to inform patients with benign prostatic hyperplasia (BPH) about their condition and treatment options and to determine its impact on perceived knowledge and treatment preference. METHODS: Six hundred seventy-eight patients with symptomatic BPH from eight Canadian centers viewed the SDP. Before and after viewing the video, patients answered questionnaires designed to assess treatment preference, knowledge gained, and satisfaction with this educational format. A 1-year follow-up survey was also conducted. RESULTS: Most patients showed a high desire for information and high satisfaction with the SDP; this satisfaction persisted at 1 year. Patients' self-reported knowledge increased significantly (P <0.0001). However, the SDP did not alter initial treatment preferences among those with already formed preferences, although it aided almost half of those initially undecided in forming a preference. Viewing the SDP also appeared to enhance the physician-patient relationship. CONCLUSIONS: Patients saw the SDP as an effective method for teaching patients about BPH and the risks and benefits of various treatments, clarifying particular areas about which many patients appear to have a desire for more information than is often provided. Patients were enthusiastic about the educational value of the program, and their active participation in the decision-making process may actually enhance the physician-patient relationship. Contrary to other studies, we found no significant alterations in treatment preferences. Problems relating to the cost and timely updating of the software need to be addressed for these kinds of programs to realize their full potential.

Aged↗

Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.

BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Adjuvants, Immunologic↗

Hyperreflexia of the urinary bladder: possible role of the efferent function of the capsaicin sensitive primary afferents.

PURPOSE: Capsaicin sensitive primary afferents (CSPA) have been implicated in the pathogenesis of hyperreflexia after spinalization. In this study we investigated the role of the efferent function of these fibers in detrusor hyperreflexia and its effect on detrusor physiology and pharmacology. MATERIALS AND METHODS: Four groups of female Sprague Dawley rats were included in our study. These groups were normal controls, capsaicin treated normal rats, spinalized rats and capsaicin treated spinalized rats. Six weeks following spinalization, animals were subjected to cystometric study, and bladders were obtained for either in vitro detrusor contractility study or substance P (SP), neurokinin A (NKA) and calcitonin gene related peptide (CGRP) quantification by radioimmunoassay. RESULTS: Spinalized animals consistently developed hyperreflexia after spinalization in the form of uninhibited contractions more than 15 cm. water in amplitude. This was accompanied by increased urinary bladder total content of the neuropeptides but without any change in the detrusor contractility or neurokinin receptor pharmacology as shown by responses to KCl, electric field stimulation and neurokinin receptor selective agonists in the in vitro study. In the control group, urinary bladder total content of SP, NKA and CGRP was 0.19+/-0.03, 0.15+/-0.01 and 0.84+/-0.1 pmol/bladder respectively. In contrast, in the spinalized animals, these were 0.44+/-0.07, 0.21+/-0.03 and 2.28+/-0.34 pmol/bladder for the same peptides, respectively. Capsaicin treatment abolished hyperreflexia, which corresponded with the decrease in the neuropeptide content of the urinary bladder. The number and amplitude of the uninhibited contractions decreased dramatically. SP, NKA and CGRP reached 0.06+/-0.01, 0.07+/-0.01 and 0.44+/-0.18 pmol/bladder 2 weeks after capsaicin treatment in spinalized animals. This was associated with the occurrence of detrusor super-sensitivity to both neurokinin receptor selective agonists. CONCLUSION: This study demonstrates the importance of the efferent function of the CSPA in the pathogenesis of hyperreflexia. On the other hand, detrusor changes were shown to be a noncrucial factor in the development of hyperreflexia.

Animals↗

Outcome assessment of double-J stents during extracorporeal shockwave lithotripsy of small solitary renal calculi.

The utility of indwelling double-J ureteral stents during extracorporeal shockwave lithotripsy (SWL) of renal calculi is ill defined. We evaluated 179 patients treated with SWL for small (< 20 mm in diameter) solitary renal calculi with (N = 27) or without (N = 152) indwelling ureteral stents. There was no significant difference in the stone-free rates at 1 month (both 52%) and 3 months (61% nonstented group v 67% stented group; P = 0.45) or in the retreatment rates (13.3% nonstented group v 14.8% stented group; P = 0.60). The incidence and severity of pain/renal colic were similar for the two treatment groups. There was minimal morbidity associated with SWL in either group. Placement of double-J stents for the purpose of improving stone-free rates, alleviating pain, or preventing ureteral obstruction in conjunction with SWL of solitary renal calculi < 20 mm in diameter is unnecessary.

Evaluation Studies as Topic↗

Apomorphine versus mating behavior in testing erectile capabilities of diabetic rats.

OBJECTIVES: Diabetes mellitus (DM) is an important cause of organic impotence. It is estimated that 35% to 75% of diabetic patients are impotent. In the present study we investigated the effect of experimentally induced diabetes (streptozocin 60 mg/kg, intraperitoneally, for 9 weeks) on sexual behavior and compared it to the apomorphine (APO) bioassay test. METHODS: Libido, genital reflex excitability, and penile competence as measured by different parameters of mating behavior were reduced with DM (P < 0.05 versus control for each parameter). RESULTS: Of 17 diabetic rats, 53% (9 rats) experienced positive mating behavior (either intromission or ejaculation) compared with 82.4% (14 rats) positive response to the APO bioassay test. Moreover, combined apomorphine injection and mating sexual testing in diabetic rats that achieved intromission but not ejaculation or those that did not achieve intromission in the initial mating, considerably improved the performance of these rats. CONCLUSIONS: We suggest that the APO test alone or, even better, combined APO injection and sexual testing are superior in eliciting maximum erectile capabilities of the diabetic rats than mating testing alone.

Animals↗

A minipig model for urodynamic evaluation of infravesical obstruction and its possible reversibility.

PURPOSE: The aim of our study was to create reproducible partial bladder outlet obstruction and to evaluate the resulting urodynamic changes. MATERIALS AND METHODS: Thirty-one female Yucatan microswine were randomly divided into obstructed and control groups. In the obstructed group of 21 animals, an artificial 4.5-cm. sphincter cuff was placed around the bladder neck. Fourteen of these minipigs were eventually deobstructed. In the controls (unobstructed sham-operated group), the sphincter cuff was removed prior to closure. Urodynamic measurements were conducted at 2, 4, 8 and 12 weeks postobstruction in conscious animals restrained in specially designed adjustable cages. RESULTS: (with all pressures in cm.H2O): 1) Unobstructed sham controls: Pdet,open 28.8 Pdet (Qmax) 22.5, Qmax 30.8 ml. per second, Pdet,isv 61.7, urethral resistance relation (URA) 7.7 cm.H2O, and Watts factor (WF) 4.7 W/m.2; 2) Obstructed group: Pdet,open 85.2; Pdet (Qmax) 94.4, Qmax 5.6 ml. per second, Pdet,isv 135.2, mean URA 74.3 cm.H2O and WF 13.5 W/m.2; 3) Deobstructed group: Pdet,open 39.9, Pdet (Qmax) 25.9, Qmax 25.0 ml. per second, Pdet,isv 58.0, mean URA 8.9 cm.H2O and WF 5.4 W/m.2. CONCLUSION: This animal model of reversible infravesical obstruction has given consistent and reproducible pressure flow data in the conscious, upright state.

Animals↗

Conscious minipig model for evaluating the lower urinary tract.

An animal model using minipigs to study urodynamic pressure flow relationships in the conscious animal is described. Port-catheters were implanted subcutaneously in the backs of 22 minipigs with access to the bladder (to measure intravesical pressure Pves) and to the peritoneal cavity (to measure abdominal pressure Pabd). The subtracted pressure (Pdet = Pves = Pabd) was recorded during the storage phase following Furosemide diuresis. Simultaneously, measurement of urinary flow (Q) during voiding was also recorded. Urodynamic studies were performed satisfactorily in all animals, and normal urodynamic profiles in minipigs were established. The minipig model allows reliable and reproducible measurement of pressure-flow parameters in a conscious state and in the natural posture.

Animals↗

Dog as an animal model for neurostimulation.

The dog provides an important model to study the effect of neural stimulation of different parts of the central and peripheral nervous systems. A multitude of experiments on neurostimulation and neuromodulation to ensure bladder evacuation have been conducted on dogs. The present article reviews the most prominent contributions in the English literature related to neurostimulation using the dog as an experimental model. The various modes of stimulation using dogs as a model and the rationale for their use as well as their shortcomings will be examined. The prominent anatomic features in the neural control of the bladder and the technical aspects involved in neurostimulation of the canine bladder will be reviewed.

Animals↗

Effect of balloon dilation of ureter on upper tract dynamics and ureteral wall morphology.

Sixteen male Yucatan minipigs underwent balloon dilation of the right ureterovesical junction (UVJ) and lower ureter to twice its normal caliber. With the bladder open, bilateral upper tract dynamics measurements under different perfusion rates (0.5, 2, and 4 ml/min) were recorded predilation, immediately after dilation, and 1, 2, 3, 4, and 6 weeks after dilation. Immediate and late antegrade nephrostograms, suprapubic cystograms, and right antegrade nephrostograms (oblique view) were taken. In the chronic experiment, no difference in renal pelvic pressure (Ppvs) was detectable between the control and dilated sides immediately after dilation. Only at 4 ml/min was there a statistically significant increase in the Ppvs of the dilated ureter 1 week after dilation when compared with the controls. At 2 weeks, this obstructive change had disappeared. At 3, 4, and 6 weeks, Ppvs of the dilated ureter declined progressively in comparison with the control side, but the difference was not statistically significant. At 6 weeks, Ppvs of the dilated ureter decreased significantly compared with predilation readings only at 4 ml/min. Immediate antegrade radiologic evaluation revealed that 69% of the experimental animals had no extravasation, while 31% showed variable degrees of extravasation, which disappeared completely on late antegrade nephrostograms (6 weeks). Grade 2 reflux occurred in 33% of the experimental animals at 1 week and had disappeared at 6 weeks. Histologic examinations at 1, 2, and 3 weeks revealed a nonhomogeneous pattern of ureteral damage, ranging from total rupture to much less dramatic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Digital subtraction cavernosography: method to detect venous leakage.

Cavernosography has become an important diagnostic test for detecting venous leakage as a cause of vasculogenic impotence. Digital subtraction cavernosography (DSC) was carried out on 21 patients with a history of venous leakage resulting in impotence. The DSC technique was compared to conventional cineradiography. Major venous leaks were easily identified in 16 patients. DSC was able to detect minor leaks missed by cineradiography in 2 patients. DSC seems to be a reliable technique that is easy to perform. It should be done in conjunction with pharmacologically induced erection.

Angiography, Digital Subtraction↗

Total androgen ablation: Canadian experience.

A multicenter randomized, double-blind trial comparing total androgen blockade obtained by the use of castration with a pure anti-androgen (nilutamide) with simple castration was begun. One hundred and five patients received the combined treatment and 103 the orchiectomy plus placebo. Several features were used to evaluate the efficacy. Bone pain responded better to combined treatment at 6 months (P = 0.042). The number of favorable responses, as evaluated by the NPCP criteria, was 61% with simple castration and 78% with the combined treatment (P = 0.013). There was no statistically significant difference between the two groups in time to progression (logrank test P = 0.462) or survival (logrank test P = 0.137) despite an increase in median survival of 5.4 months. All other measures showed no difference between the two treatments. With total androgen blockade, 50% of the patients had disease progression at 1 year, and 45% were dead at 2 years. A review of the results of similar reported studies suggests no improvement or very modest improvement with total androgen blockade over testicular androgen ablation alone.

Adult↗

A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma.

A randomized double-blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti-androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression-free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma.

Adult↗