Erectile dysfunction in the Africa/Middle East Region: epidemiology and experience with sildenafil citrate (Viagra).
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Africa↗
Biomedical subjects
I M Khalaf
Publications and source records attributed to I M Khalaf.
Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa.
The efficacy of sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been demonstrated in global studies. This 12-week randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study assessed the efficacy and safety of sildenafil to treat ED in men in Egypt and South Africa. Men with ED of varied etiology were randomized to receive sildenafil 50 mg (n=128) or placebo (n=126); doses could be adjusted to 100 or 25 mg. Questions from the International Index of Erectile Function (IIEF) assessing the ability to achieve (Q3) and maintain (Q4) erections demonstrated a significant improvement with sildenafil compared with placebo (P<0.0001). Improved erections were reported by 74% of patients receiving sildenafil and 27% of those receiving placebo (P<0.0001). Headache, dyspepsia, and flushing were the most common adverse events in sildenafil-treated patients. These results are consistent with clinical trials in other countries. We conclude that sildenafil is an efficacious and well-tolerated treatment for men with ED in Egypt and South Africa.
Adult↗
Effects of verapamil, prostaglandin F2 alpha, phenylephrine, and noradrenaline on upper urinary tract dynamics.
OBJECTIVES: The effects of verapamil (VRP), prostaglandin F2 alpha (PGF2 alpha), phenylephrine, and noradrenaline on upper urinary tract dynamics were studied in vivo, using a pig model involving 12 miniswine which were subjected to acute pharmacologic perfusion studies of the upper urinary tract. METHOD: Changes in renal pelvic pressure (Ppvs) and ureteral peristalsis frequency were recorded at 2 mL/min perfusion rate premedication, and then during perfusion with different concentrations of each drug tested in three experiments. RESULTS: Ppvs showed no significant variations with VRP perfusion when compared with premedication readings, whereas ureteral peristalsis frequency was decreased significantly by 10(-3) mol/L of VRP. PGF2 alpha perfusion caused no statistically significant changes in Ppvs when compared with premedication values, but increased ureteral peristalsis frequency from 3 to 6.5/min at a concentration of 2 x 10(-1) mg (200 micrograms). Phenylephrine HCl and noradrenaline perfusion increased Ppvs from 8 +/- 1.1 to 11.9 +/- 1.6 cm water at a concentration of 100 micrograms. They augmented the frequency of ureteral peristalsis from about 2.5 +/- 1.2 to 4.1 +/- 1.3/min. No systemic effects were recorded since pulse, respiration, and left ureteral activity were unchanged during pharmacologic perfusion of the right side. CONCLUSION: Pharmacologic manipulation of ureteral activity can be achieved via direct perfusion with no significant modulation of Ppvs or systemic impact. VRP-induced smooth muscle relaxation of the upper urinary tract may be useful in percutaneous surgery for stones.
Animals↗
Healing and muscular restoration of the ureteral wall following balloon-induced rupture: an experimental animal model with light microscopic and ultrastructural observations.
Ureteral regrowth following balloon-induced rupture was studied using an animal model, with emphasis on the pattern and cellular events of self-reconstitution in the late phase of healing. At 4 weeks, the ureteral healing/remodeled region included a wedge-shaped muscular component which pointed toward a fibrous central zone, was continuous with the adjacent muscularis propria, and abutted on a thin-lining epithelium. Progressive enlargement, aggregation, and bundle formation of myogenic cells was observed along the centrifugal axis. At 7 weeks, there was near-total muscular continuity, a rudimentary lamina propria, and partial periluminal folding. Muscular restoration was unaffected by the use of a stent, but epithelial metaplastic changes were observed. The intermediate zone showed admixed fibroblasts, immature and mature myogenic cells, and myofibroblasts. Frequent plasmalemmal appositions and junctions were observed between different cell types, whereas myofibroblasts were not associated with cell-to-stroma attachments. Myofibroblasts might play more than a contractile role in this phase of ureteral healing, possibly having an induction role and/or representing a transient form in myogenic differentiation.
Animals↗
Long-term effects of ureteric stent after ureteric dilation.
Balloon dilation of the right ureterovesical junction (UVJ) and distal ureter to three times its normal caliber was performed in 12 pigs. A right double-J (D-J) stent was inserted after dilation in 6 pigs. Bilateral upper tract dynamics with different perfusion rates (0.5, 2 and 4 ml. per minute) were recorded before dilation, immediately after dilation, and then 4 and 7 weeks after dilation. Immediate and late antegrade nephrostograms as well as suprapubic cystograms were taken. Grade 3 reflux occurred in 100% of animals at 7 weeks on the dilated, stented ureter and no reflux on the dilated, nonstented ureter. At 7 weeks on the dilated, stented side, significant growth (> 100,000, colonies) of Pseudomonas species was noted in all animals. Creatinine clearance was significantly reduced on the dilated, stented side when compared to the dilated, nonstented side at 7 weeks. Histologic examination of the dilated, stented and dilated, nonstented ureters at 4 weeks revealed a segmental muscular defect with muscular regeneration starting from the edge of the defect, particularly in the innermost region. At 7 weeks, there was a more advanced, but similar, pattern of muscular regeneration in both groups. However, at 7 weeks, metaplastic changes of the ureter and chronic pyelonephritis were evident on the dilated, stented ureter. Electron microscopy showed that myofibroblasts played a major role in the healing process with new muscle formation. At 4 weeks, no significant morphologic difference was found between the dilated, stented and dilated, nonstented ureters. At 7 weeks, however, it appeared that the ureteric stent resulted in damage and deterioration of renal function without affecting muscular regeneration of the ureter. We conclude that the changes observed could be entirely due to the infection associated with the stent rather the stent itself.
Animals↗
The effect of exogenous prostaglandins F2 alpha and E2 and indomethacin on micturition.
The influence of exogeneous infusion of prostaglandins (PGs) of the F2 alpha and E2 series and of indomethacin on micturition cycles was investigated in 30 anaesthetised female dogs. In 30 other animals, urethrovesical disconnection was performed to study the action of PGs and of indomethacin without the muscle continuity factors. In the intact animal model during vesical distension, PGE2 produced a significant urethral pressure drop and a dose-dependent reduction in the threshold micturition volume. PGF2 alpha produced a significant urethral pressure rise. At doses higher than 0.3 micrograms/kg, PGF2 alpha reduced the threshold micturition volume. On the other hand, indomethacin significantly increased the threshold micturition volume and reduced the maximum intravesical pressure. In the disconnected model, PGE2 produced a dose-dependent decrease in the resting urethral pressure and hardly affected the intravesical pressure; PGF2 alpha produced a dose-dependent increase in both urethral and intravesical pressures. Thus it is suggested that endogenous PG release during vesical distension could play a facilitatory role in micturition.
Animals↗
Intravesical prostaglandin: release and effect of bladder instillation on some micturition parameters.
Bladder washout effluent fluid was examined for prostaglandin-like activity following acidic lipid extraction and bioassay using the rat-stomach strips technique. A low basal level of prostaglandin-like material was detected in washouts collected when the bladder was empty in 4 out of 7 dogs. Increased levels were detected following micturition in 5 of these 7 dogs. A significantly high level of prostaglandin-like material was recovered after pelvic nerve stimulation. The prostaglandin-like material was tentatively identified as PGE based on the bioassay with the addition of specific antibody. Intravesically administered PGE2 or PFG2 alpha significantly reduced, in a dose-dependent response, the threshold micturition volume. All of these findings suggested that prostaglandins may play a role in the micturition process.
Animals↗
Release of prostaglandins into the pelvic venous blood of dogs in response to vesical distension and pelvic nerve stimulation.
Prostaglandin release into the pelvic venous blood in response to vesical distension and pelvic nerve stimulation was studied in anesthetized female nonpregnant dogs. The change in the prostaglandin content of the plasma at sequential physiologic points in the voiding cycle and with pelvic nerve stimulation was measured using a radioimmunoassay technique. A significant liberation of PGE and PGF2 alpha was observed during maximal bladder distension and after micturition. The increased levels returned to near control levels when measured 5 min after bladder evacuation. After pelvic nerve stimulation, PGF2 alpha was also significantly released. The source, mechanism, and functional significance of prostaglandin release during bladder activity are discussed.
Analysis of Variance↗
Urethral pressure changes in reflex micturition.
The mechanism and pattern of urethral pressure changes during bladder filling and voiding were investigated in anesthetized female dogs. A series of experiments was performed involving simultaneous recording of intraurethral and intravesical pressures before and after surgical separation of the bladder from the urethra. Similar experiments were done after pharmacologic blockade of the striated muscles, alpha-adrenergic receptors, and autonomic ganglia. The urethral pressure rise during the collection phase and its drop simultaneous with bladder contraction were observed both before and after vesicourethral interruption. Tubocurarine did not block pressure changes recorded in the proximal urethra. Phentolamine did not prevent a urethral pressure drop simultaneous with detrusor contraction. After effective blockade of autonomic ganglia by pentolinium, reflex micturition could not be induced by bladder filling. However subsequent administration of bethanechol chloride induced a bladder pressure rise together with a simultaneous drop of urethral pressure. We conclude that both vesicourethral muscle continuity and autonomic reflexes contribute to the urethral pressure changes during the two phases of bladder activity, passive collection and active expulsion.
Animals↗
The effect of dantrium on the canine urethral pressure profile.
The effects of dantrolene sodium and tubocurarine on the urethral pressure profile were investigated in anesthetized dogs. A model of urethrovesical separation was used to prohibit transmission of pressure changes between the bladder and urethra. Intravesical pressure (representing smooth muscle activity) and arterial blood pressure (for cardiovascular effects) were recorded simultaneously. Tubocurarine and dantrolene sodium in pharmacologic doses had equally depressive effects on the urethral pressure profile at its distal three-fifths although a longer duration of action was observed with dantrolene. The depressive effect of dantrolene was dose-dependent. Although dantrolene sodium had no effect on blood pressure or heart rate, it did depress intravesical pressure at the 15 mg per kg of body weight dose. These findings would seem to suggest the use of dantrolene sodium in urodynamic experimental studies.
Animals↗