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Biomedical subjects

R Shabsigh

Publications and source records attributed to R Shabsigh.

At least 55 records · Page 3Linked to original sources

The effects of testosterone on the cavernous tissue and erectile function.

A review of the current literature is conducted to explore the developmental aspects, animal and human experiences and the effects of pharmacological manipulation to explain the role androgens play in sexual function with special emphasis on erectile function and the erectile tissue. This review reveals that androgens are necessary for the normal development of the penis and their deficiency results in significant structural abnormalities. Although androgen receptors in the penis decrease after puberty, they usually do not disappear completely. Animal data show that androgens support erectile function through a direct effect on the erectile tissue. Experimental castration results in impaired erectile response to central and peripheral stimulation and decrease in penile tissue concentration of nitric oxide synthase-containing nerves. Testosterone replacement reverses these abnormalities. In the rat penis, apoptosis is induced by castration and new DNA synthesis is induced by testosterone replenishment. Human data are less clear than animal data. Castration results in loss of libido and in erectile dysfunction. However, these effects are not universal. Testosterone enhances libido, frequency of sexual acts and sleep-related erections. Its effects on erotic erections are not clear.

Androgens↗

Apoptosis in the rat penis after penile denervation.

PURPOSE: Despite the advances in nerve sparing prostatectomy for prostate cancer, some patients develop impotence or subjectively complain of a decrease in penile size. We hypothesized that these clinical observations may be explained by injury to the cavernous nerves resulting in programmed cell death (apoptosis) within the penis. We utilized a rat model of penile denervation in order to demonstrate apoptosis after denervation. METHODS AND MATERIALS: Fifteen male Sprague Dawley rats underwent abdominal exploration and bilateral cavernous neurotomy. Fifteen sham operations were performed as normal controls. The rats were sacrificed on postoperative day 1,2,3,6, and 10 and their penises were harvested. Messenger RNA was extracted and probed on a northern blot for sulfated glycoprotein-2 (SGP-2). SGP-2 is a gene product reported to be elevated in apoptotic tissues. Separate denervated and sham rats were used for DNA extraction (sacrificed postoperative day #2) in order to demonstrate the internucleosomal DNA fragmentation (laddering) found in apoptotic tissues. In addition, in situ histology was performed with ISEL techniques (in situ end labeling) to stain for apoptotic nuclei in denervated rats. RESULTS: Northern blot analysis showed a large increase in SGP-2 mRNA expression in the denervated rats with little detected in the sham operated group. DNA extraction studies revealed the presence of internucleosomal DNA fragmentation on agarose gel (a marker for apoptosis) in the denervated group versus intact high molecular weight DNA in the sham rats. In addition, in situ staining of denervated penile erectile tissue demonstrated apoptotic nuclei in the cavernous tissue. CONCLUSION: Apoptosis of penile erectile tissue occurs after denervation of the rat penis. This has not been previously described in the literature and may offer some explanation at the molecular level concerning the mechanism of impotence and/or decrease in penile size after radical prostatectomy.

Animals↗

Transperineal prostate needle biopsy guided by transurethral ultrasound in patients without a rectum.

OBJECTIVES: Patients with elevated prostate-specific antigen (PSA) and no access to the rectum present a diagnostic challenge to the urologist. This study was undertaken to determine the efficacy of transperineal prostate biopsy using transurethral ultrasound guidance for the detection of prostate cancer. METHODS: Five men status post either total colectomy or abdominoperineal resection (age range: 58 to 73 years, mean age 65.8 years) were referred to us for the evaluation of an elevated PSA (range: 5.6 to 21.4 ng/dL, mean 16.1 ng/dL). Seven procedures were performed utilizing transurethral ultrasound to guide transperineal prostate biopsies in these men. RESULTS: Biopsy results revealed benign prostatic hyperplasia in 4 procedures and prostate cancer in 3 procedures. CONCLUSIONS: Transurethral ultrasound enables the practitioner to perform accurate sonographic assessment and precise biopsy of the prostate in such patients.

Aged↗

Laser tissue soldering in urinary tract reconstruction: first human experience.

OBJECTIVES: Laser tissue soldering (LTS) in the urinary tract provides an immediate leak-free seal and may avoid complications seen with conventional repair (such as fistula and stricture). We have begun a Phase I clinical trial investigating the use of LTS in performing urologic reconstructive surgery. METHODS: Ten patients (aged 3 months to 38 years) underwent urologic reconstruction using LTS with a protein solder composed of human albumin (42%) and indocyanine green dye. In each case standard microsuture repair preceded laser-soldered suture line reinforcement. Anastomotic closure time and immediate leak pressure were measured. Postoperatively, all patients were evaluated for evidence of complications, including stricture, fistula formation, or impaired healing. RESULTS: Using LTS as an adjunct to suturing added an average of 7.9 +/- 3.0 minutes (28%) to the overall mean anastomotic time of 28.3 +/- 9.4 minutes. Intraoperative leak pressure measurements for laser-soldered anastomoses (> or = 94.2 +/- 24.2 mm Hg) were significantly higher (P < 0.001) than primarily sutured anastomoses (20 +/- 2.9 mm Hg). Two instances of suture disruption (20%) occurred during laser activation, neither of which were repaired with sutures. Average follow-up for all patients was 7.1 + - 2.2 months. There were no intraoperative or postoperative complications, including the 2 patients with suture disruption. CONCLUSIONS: These initial clinical results indicate that LTS is safe, easy to perform, and, contrary to conventional suturing, provides an immediate leak-free closure. Follow-up in these and other patients, as well as those undergoing sutureless and stent-free procedures, will determine whether our method of LTS benefits patients undergoing urologic reconstruction.

Anastomosis, Surgical↗

Laser welding versus suturing in tunica vaginalis and venous patch graft corporoplasty.

Congenital penile curvature may result from corporeal disproportion in nearly 40% of cases, while in adults scarring of the corporeal bodies or periurethral fibrosis accounts for the majority of cases. Some surgeons advocate lengthening the fibrosed corporeal bodies by excising tunica albuginea and grafting such defects to straighten the penis. Tunica vaginalis, dermis, dorsal vein and lyophilized dura have been used for this purpose. Traditionally, these graft biomaterials have been sutured to the tunica albuginea. We assessed the feasibility, short-term safety and efficacy of diode laser tissue welding using albumin based solder and indocyanine green dye to perform patch graft corporoplasty in the dog. Ten animals were subjected to bilateral transverse excision of 1 x 2 cm. sections of tunica albuginea. Corporoplasty was performed using grafts composed of saphenous vein (5) or tunica vaginalis (5). Microsurgical repair with 7-zero polydioxanone suture (10) was compared to contralateral laser welded repair (10) by recording operative time, initial and short-term bursting pressures (mean plus or minus standard deviation) and histological analysis. Operative time on the laser side (9.8 +/- 2.3 minutes) was significantly shorter (p < 0.05) than on the suture side (17.1 +/- 5.1 minutes). Leak pressures, initially (laser 105.7 +/- 23.8 mm. Hg versus suture 35.3 +/- 8.0 mm. Hg), at 3 to 5 days (greater than 333.3 +/- 62.4 mm. Hg versus 136.6 +/- 39.4 mm. Hg) and at 7 to 10 days (greater than 397.8 +/- 39.8 mm. Hg versus 191.5 +/- 46.4 mm. Hg) were higher (p < 0.05) in the laser side compared to controls. Graft failure (necrosis) occurred in 3 repairs (2 laser on day 4 and 1 suture on day 10). Viable tissue with minimal differences in foreign body reaction between groups was observed in the remaining grafts. We conclude that laser welded patch graft corporoplasty using tunica vaginalis or vein is easy to perform, and provides excellent initial and short-term leak pressures. The use of laser welding in conjunction with suturing may be beneficial in corporoplasty for congenital or acquired penile curvature.

Animals↗

Neurotrophic factors in the rat penis.

An intact nerve supply is essential for normal erectile function. We have undertaken a study to examine the presence and synthesis of growth factors of the penis that support neural function. Extracts were obtained from deskinned penises of Sprague-Dawley rats, aged 3, 6 and 10 weeks, representing prepubertal, pubertal and postpubertal states. Penile extracts were subjected to Northern blot analysis to evaluate expression of nerve growth factor-beta (beta-NGF)-mRNA, PC-12 bioassay to quantitate the nerve growth promoting activity and immunoassay to detect the amount of beta-NGF protein. These initial experiments showed a disproportionately abundant level of nerve growth promoting activity as compared with the levels detected with the immunoassay. The PC-12 bioassay is sensitive to both beta-NGF and fibroblast growth factors (FGFs). To further investigate these findings, the bioassay was conducted again after heparin chromatography, with beta-NGF receptor blockade, or with the addition of anti-beta-NGF, anti-basic-FGF, or anti-acidic-FGF. These studies confirmed that the abundant nerve growth promoting activity in the rat penis is due largely to basic FGF. In conclusion, the neurotrophin NGF is expressed in the rat penis at levels consistent with its expression in other peripheral tissues. Basic-FGF, on the other hand, has been detected at levels far in excess of NGF. Since erectile function is dependent on the integrity of the vascular structure and its intact innervation and since basic FGF presents as an abundant penile growth factor with both angiogenic and neurotrophic activities, basic FGF might play a significant role in erectile physiology.

Animals↗

Percutaneous approach to treatment of Indiana pouch stones.

Continent urinary diversions have gained popularity during recent years in the treatment of patients who require cystectomy. The formation of urinary stones remains a possible late complication of urinary diversion. We report the successful use of a percutaneous approach to remove stones from an Indiana pouch after other methods failed.

Combined Modality Therapy↗

Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat.

We describe early alterations in rat bladder gene expression which may relate to the development of diabetic bladder dysfunction in a streptozotocin model of inducible diabetes. Utilizing cDNA probes, the gene products sulfated glycoprotein-2 (SGP-2), transforming growth factor-beta (TGF-beta), beta-actin (beta-actin), N-ras and beta nerve growth factor (beta-NGF), were quantitated in bladders of male Sprague-Dawley rats at 1, 2, 4 and 6 weeks after induction of diabetes with streptozotocin (STZ). beta-actin and SGP-2 expression were transiently increased at 1 and 4 weeks after induction, respectively. TGF-beta was not altered over the period of the study. N-ras was reduced at all times compared with control rat bladders. Transcripts encoding beta-NGF were dramatically increased in STZ-treated rats at 4 weeks. None of these changes were seen in diuresis control group fed 5% sucrose. Our results suggest that during the early stages of diabetes, cellular hypertrophy, growth and remodeling are occurring concomitantly with cellular injury and programmed cell death. Furthermore, the transient increase in expression of beta-NGF mRNA may represent a compensatory response to the diabetic condition in an attempt to attract further innervation and revascularization.

Actins↗

Percutaneous transvesical ureteroscopy for removal of distal ureteral stone in reimplanted ureter.

In the past two decades, the widespread use of cross-trigonal ureteral reimplants for the treatment of children with vesicoureteral reflux has resulted in a large population of patients with transversely lying ureters. As this population gets older they will consequently be entering an age group at higher risk for stone and urothelial cancer formation, with the potential for diagnostic and/or therapeutic ureteroscopy. The anatomic orientation of the ureters resulting from a cross-trigonal reimplantation may create difficulty or even inability to perform transurethral ureteroscopy. This case presents the technique of percutaneous transvesical ureteroscopy for stone extraction in a seventeen-year-old male with a lower ureteral stone following cross-trigonal ureteral reimplantation. The described technique may serve as an addition to the current endoscopic methods.

Adolescent↗

Transrectal hyperthermia in the management of men with prostatism: an algorithm for therapy.

Transrectal hyperthermia has been proposed as a potential treatment for benign prostatic hyperplasia (BPH). This report presents our initial experience in an ongoing clinical trial to evaluate the safety and efficacy of transrectal thermal therapy (TRTT) for symptomatic BPH. To date, 24 patients (mean age 60.6 years) have undergone TRTT. In all cases the initial investigations included pre-operative symptom score analysis, synchronous video/pressure/flow urodynamic studies and transrectal measurement of both the size of the prostate and the distance between the applicator and the prostatic urethra (AU). Twenty-one patients completed the study (mean follow-up 6.7 months). There was a significant reduction in symptom score (> 50%) in 14 patients and the peak urinary flow rate (Qmax) increased from 5.9 to 12.4 ml/s at 1 month, 12.7 ml/s at 3 months and 13.2 ml/s at 6 months. In 12 patients the decrease in symptom score and the increase in flow rate exceeded 50%. Five of the 6 patients who failed to respond to treatment had prostate volumes > 85 g; 4 had voiding detrusor pressures < 40 cm H2O and 5 had an AU distance > 2.5 cm. These preliminary results suggest that TRTT may be a potential therapeutic alternative in patients with mild to moderate symptoms of prostatism. However, patients with either lower detrusor pressures (< 40 cm H2O) or very large prostates are unlikely to show a beneficial response. We suggest that large prostates may preclude effective temperature distribution and therefore mitigate the potential therapeutic benefit.

Adult↗

Prostatic and periprostatic interstitial temperature measurements in patients treated with transrectal thermal therapy (local intracavitary microwave hyperthermia).

One of the questions raised regarding the use of transrectal thermal therapy in the treatment of benign prostatic hyperplasia (BPH) is whether there is a uniform and safe temperature distribution within the prostate. Our study represents the first attempt in humans to map the interstitial thermal distribution in the prostate during transrectal thermal therapy. With the patient under local anesthesia and under ultrasound guidance, a transperineal 3-point thermocouple was placed into various areas of the prostate in 15 patients. Prostatic-urethral thermocouple distance ranged from 1 to 3 cm. A urethral catheter containing a 5-point linear array thermocouple was placed and the balloon was inflated so that the proximal point was at the bladder neck and the remaining points were at 1 cm. intervals along the prostatic urethra. Power (25 watts) was delivered via the Primus (Technomatix) transrectal microwave applicator with simultaneous cooling of the rectal mucosa (between 12 and 14C). Treatment was delivered for 60 minutes and temperatures were recorded. In the prostatic substance a maximal temperature of 45C was observed during the heat-up phase and this decreased as the vasoactive response occurred. Temperature along the prostatic urethra varied between 40 and 43C and never exceeded 44C. A similar distribution of temperature was registered in the thermocouple points in the prostatic substance. The anticipated thermal dose of 41.5 +/- 1C for 60 minutes was achieved in the prostatic substance as measured by the sensors in the prostatic urethra and interstitial sensors. The results suggest that transrectal thermal therapy delivers a uniform and safe distribution of heat in the prostatic substance and urethra. Clinical trials are currently underway to ascertain the efficacy of transrectal thermal therapy in the management of BPH.

Adult↗

Venous leaks: anatomical and physiological observations.

A total of 50 patients with impotence underwent cavernosometry and cavernosography with intracavernous injection of vasoactive drugs. Several hemodynamic parameters were analyzed, including the pressure response curve after injection of vasoactive drugs and infusion of saline, the volume required to achieve erection, venous outflow resistance, erection maintenance infusion rate, rate of pressure decrease after discontinuation of infusion and post-infusion steady state pressure. On the basis of cavernosometric findings, venous leakage was ruled out in 4 patients. In the remaining 46 patients leak sites visualized during cavernosography included superficial dorsal vein in 1 (2.2%), deep dorsal vein in all 46 (100%), cavernous veins in 32 (69.6%), glans in 19 (41.3%) and corpus spongiosum in 14 (30.4%). Aberrant veins were documented in 7 patients (15.2%) communicating with the saphenous vein in 4 (8.9%), scrotal veins in 2 (4.4%) and femoral veins in 1 (2.2%). Eight patients (17.4%) had leakage through the deep dorsal vein as the only venous site, 17 (36.9%) had leakage through 2 venous sites, 14 (30.4%) had leakage through 3 venous sites and 7 (15.2%) had leakage through 4 venous sites. Correlations among hemodynamic and radiographic observations allowed the identification of 4 different types of cavernosometric findings. While type I represented normal penile vascular findings, types III and IV represented venous leakage. Type II could represent no leak, a mild leak or an undetected arterial problem. Accuracy of interpretation of a study may be improved by taking more than 1 parameter into consideration, including erection maintenance infusion rate, intracavernous pressure decrease within the first 5 seconds after discontinuation of infusion and the final steady state intracavernous pressure. The majority of patients have more than 1 leak site (82.6%). The most commonly combined sites of leakage are the deep dorsal and cavernous veins.

Adult↗

Cigarette smoking and other vascular risk factors in vasculogenic impotence.

A total of 132 consecutive patients with erectile impotence underwent extensive evaluation, including vascular evaluation with intracavernous injection of papaverine and penile duplex ultrasonography, to determine the etiology of impotence. Three vascular risk factors, smoking, diabetes mellitus and hypertension, were investigated for their impact on vasculogenic impotence. The patients were divided into four groups: one with no risk factors, one with one vascular risk factor, one with two vascular risk factors, and one with all three risk factors. The results of penile vascular evaluation in these patient groups were compared. The incidence of penile vascular impairment was found to be higher in patients with one vascular risk factor than in those with none. The proportion of abnormal penile vascular findings significantly increased as the number of risk factors increased. These data confirm the important role of vascular risk factors, smoking, diabetes mellitus, and hypertension, in the pathogenesis of organic impotence.

Diabetes Mellitus↗

Comparison of penile duplex ultrasonography with nocturnal penile tumescence monitoring for the evaluation of erectile impotence.

A total of 50 patients with erectile dysfunction underwent comprehensive evaluation, including vascular evaluation with penile duplex ultrasonography and papaverine injection, as well as nocturnal penile tumescence monitoring. The latter was performed in a sleep laboratory setting in all patients. The results of penile duplex ultrasonography with papaverine injection were classified as 18 patients with normal vascular findings, 22 with arterial insufficiency, 3 with the pelvic steal syndrome and 7 with isolated venous leakage. Of the patients 15 had normal ultrasonographic and nocturnal penile tumescence findings, 29 had abnormal ultrasonographic vascular and nocturnal penile tumescence findings, 3 had abnormal ultrasonographic vascular findings and normal nocturnal penile tumescence (including 1 with the pelvic steal syndrome as evidenced by penile brachial index) and 3 had normal ultrasonographic vascular findings and abnormal nocturnal penile tumescence (including 2 with neurogenic erectile dysfunction). Penile duplex ultrasonography with papaverine injection appears to be a useful objective method to evaluate vasculogenic impotence and to correlate favorably with nocturnal penile tumescence monitoring. It also may have a higher yield than nocturnal penile tumescence monitoring in patients with the pelvic steal syndrome. While nocturnal penile tumescence is impaired in patients with neurogenic impotence, penile duplex ultrasonography with papaverine injection reveals, as expected, normal findings in patients with neurogenic impotence and normal vascular systems.

Adult↗

Evaluation of vasculogenic erectile impotence using penile duplex ultrasonography.

A total of 140 patients underwent penile vascular evaluation with intracavernous papaverine injection combined with duplex ultrasonography. Of these patients 8 were potent men who were evaluated for reasons other than erectile failure. These potent men were used as controls to obtain normal values. The remaining 132 patients had erectile impotence of various etiologies. Real-time imaging with high resolution, high frequency probes allowed for visualization of the cavernous arteries along the entire length in addition to accurate measurement of the diameter. Simultaneous selectively focused Doppler ultrasonography was used to measure the blood velocity and other vascular parameters in the cavernous and dorsal arteries. Comparison of measurements before and after papaverine injection allowed for objective interpretation of the injection results. The results were analyzed and compared to other data available on the same patients, such as history and physical examination, nocturnal penile tumescence, penile blood pressures, selective arteriography and dynamic cavernosography. In addition to the 8 potent men, there were 35 patients (27% of the impotent patients) whose vascular findings were normal. A total of 78 patients (59% of the impotent patients) had arterial insufficiency; a subgroup of 13 patients had the pelvic arterial steal syndrome. Dynamic cavernosography confirmed venous leak in all 19 patients (14% of the impotent patients) whose penile duplex ultrasonography suggested the possibility of a venous leak. Ten patients (7%) had prolonged erection after papaverine injection and they were managed without consequences. One patient had a small hematoma that resolved uneventfully. Penile duplex ultrasonography was a helpful and objective method to evaluate vasculogenic impotence.

Adult↗

Experience with the artificial urinary sphincter model AS800 in 148 patients.

The latest version of the artificial urinary sphincter, AS800, was used in 148 patients with urinary incontinence of different etiologies. Followup ranged from 3 to 37 months, with an average of 20.8 months. There were 112 (76 per cent) male and 36 (24 per cent) female patients. The cuff was implanted around the bladder neck in 78 patients (53 per cent) and around the bulbar urethra in 70 (47 per cent). Socially acceptable urinary control was achieved in 90 per cent of the 139 patients with active devices in place. It was necessary to remove the sphincter in 11 patients (7.4 per cent). The reasons for removal were infection and erosion in 8 patients (5.4 per cent), infection without erosion in 2 (1.3 per cent), and erosion due to excess pressure and poor tissues in 1 (0.7 per cent). Comparison of success and failure rates associated with incontinence of different etiologies revealed that patients with incontinence after failure of a conventional antistress incontinence operation and those with incontinence after transurethral resection or radical prostactectomy had the highest success rate, and that patients with incontinence secondary to pelvic fracture or exstrophy and epispadias had the highest failure rates. The deactivation feature (the lock) of the new artificial sphincter model was beneficial for primary deactivation, urethral catheterization or cystoscopy, or for elective nocturnal decompression of the bladder neck or urethral tissues.

Equipment Design↗