Biomedical subjects

G B Brock

Publications and source records attributed to G B Brock.

28 records · Page 2Linked to original sources

PubMed1995

Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation.

Prazosin (an alpha-1-adrenergic blocker) and cromakalim (potassium channel opener), given alone, induced significant fatigue of the urethral sphincter at a concentration of 10(-4) M; both drugs combined achieved a significant sphincteric fatigue at a concentration of 10(-5) M each. To 10(-4) M hexamethonium (ganglionic smooth muscle blocker) and 10(-4) M decamethonium (nicotinic blocker of striated muscle) the striated urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated component seems to play a dominant role in sphincteric function. With calcium depletion or in the presence of a calcium channel blocker (10(-4) M nifedipine) the urethral sphincter showed a relative enhancement of response to electrical field stimulation when compared with smooth and skeletal muscle, whose responses were both significantly reduced. This phenomenon could not be explained with calcium-dependent, inhibitory, nitric oxide-releasing nerves, as the NO-synthase blocker N-nitro-L-arginine (10(-5) M to 5 x 10(-5) M) failed to induce the enhancement of sphincter contraction during electrostimulation found with calcium depletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significant relaxation of the urethral sphincter precontracted with 80 mM potassium. The potential to weaken sphincteric closure with drugs, exemplified by the results obtained in response to prazosin and cromakalim, would represent a therapeutic advance in the patient with neurogenic bladder dysfunction.

Amino Acid Oxidoreductases↗

PubMed1995

Intraoperative electrostimulation of the cavernous nerve: technique, results and limitations.

PURPOSE: We studied the feasibility of inducing penile erection intraoperatively by stimulation of the cavernous nerves. MATERIALS AND METHODS: In 16 men undergoing retropubic radical prostatectomy and 6 undergoing penile surgery for venous leakage electrostimulation was applied to both sides of the prostatic apex (prostatectomy group) or the hilum of the penis (venous surgery group). RESULTS: Electrostimulation produced visible erection in 8 of the 16 prostatectomy patients and an increase in intracavernous pressure in 5 of the 6 venous surgery patients. CONCLUSIONS: Electrostimulation of the cavernous nerves intraoperatively to produce penile erection is feasible. However, the technique must be further refined to be clinically useful, that is to localize the neurovascular bundle in men undergoing prostatectomy.

Adult↗

PubMed1995

Chronic penile denervation in the rat: effect on cavernous tissue morphology and function.

We evaluated the effects of chronic penile denervation on cavernous tissue morphology and function in 36 Sprague-Dawley rats. At age seven weeks, 18 animals underwent bilateral cavernous nerve neurectomy: 18 animals underwent sham operation as a control. A functional, biochemical and morphological assessment of the rats' penises was performed at 4 months. In denervated rats, intracavernous pressure failed to rise with electrostimulation of the pelvic plexus. However, a normal rise in pressure was found with direct intracavernous injection of sodium nitroprusside and papaverine. Sodium dodecylsulfate polyacrylamide (SDS) gel electrophoresis of the penile homogenate showed subtle differences between denervated and control animals. Based upon the histological findings there was no difference in staining of the cavernous tissue for acetylcholinesterase- and catecholamine-positive nerve fibers between experimental and control animals, since the innervation density was not quantified and the number of fibers was not counted. We conclude that chronic cavernous nerve neurectomy does not cause significant morphological or functional changes to the penile erectile tissue of rats.

Acetylcholinesterase↗

PubMed1995

Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erection model.

Classically, androgens were thought to be linked to sexual activity in man through their action on increased libido. Recently, the sex hormone dependent nature of nitric oxide synthase (NOS), the enzyme system producing the neurotransmitter of erection (nitric oxide) has been reported. Our study evaluated how changes in testosterone levels alter erectile function. In forty-seven rats the erectile response to cavernous nerve electrostimulation was recorded 1, 5, 10, 20 and 30 d post-bilateral orchiectomy, and compared to controls. Penile tissue was subsequently stained for the presence of NOS, using an NADPH diaphorase technique. Forty eight rats were used in part two. After orchiectomy exogenous testosterone was administered and the erectile function as well as density of NOS positive nerve fibers was assessed. All castrated animals showed a rapid decrease in serum free testosterone levels within 24 h. In contrast, a gradual decrease in intracavernous pressure was recorded with cavernous nerve stimulation, proportional to the time post orchiectomy. NADPH diaphorase staining showed a decreased density of nonadrenergic noncholinergic (NANC) nerve fibers innervating the cavernosal tissue proportional to the time post orchiectomy. With reconstitution of the androgen mileu the erectile response returned to near normal values and recovery of NADPH-positive nerve fibers was observed. Based on presented data we conclude that testosterone or a metabolite plays a direct role in erection acting through an effect on nitric oxide synthase within the corpora cavernosa.

Animals↗

PubMed1994

The latissimus dorsi muscle for detrusor assistance: functional recovery after nerve division and repair.

The treatment of choice for bladder atonia is clean intermittent catheterization. To eliminate the catheter-related morbidity and increase the quality of life for patients with an atonic bladder, the restoration of bladder contractility would be desirable. Based on our hypothesis that skeletal muscle might augment bladder contractility, we designed the present study to examine the ability of the latissimus dorsi muscle in situ to empty a bladder-like reservoir and to regenerate after division and repair of the supplying motor nerve. In 4 dogs, the left latissimus dorsi muscle was dissected, mobilized and wrapped around a bladder substitute (100-ml. silicone reservoir). Stimulation of the thoracodorsal nerve resulted in the evacuation of 63.8 +/- 6.2% of the reservoir's volume and a maximum pressure of 109.5 +/- 18.6 cm. H2O. Four months later, the thoracodorsal nerve supplying motor control to the muscle was transected and microsurgically reanastomosed. Using transcutaneous stimulation, we recorded the pressure generation and resulting evacuation at regular intervals for 8 months (that is, 12 months after the initial surgery). At the end of this period, the pressure was 79.3 +/- 12.1 cm. H2O (72.4% of the initial value), expelling 48.3 +/- 6.7% of total volume. This long-term study demonstrates: (1) the ability of the transposed latissimus dorsi muscle to evacuate a bladder-like reservoir; and (2) the regenerative potential of muscle and nerve after nerve transsection and repair. Use of skeletal muscle, which can be readily stimulated, may serve to facilitate bladder emptying and provide a treatment alternative to intermittent catheterization in the future.

Animals↗

PubMed1994

Laparoscopically implantable nerve-stimulating electrode (LINSE): application to the cavernous nerve in acute and chronic canine models.

Using a new laparoscopic procedure, we investigated stimulation of the cavernous nerves to achieve erection in a canine model. The technique was developed during acute experiments in four dogs, following which, chronic studies (4- to 6-weeks survival after surgery) were undertaken in three dogs. A monopolar cuff electrode was inserted laparoscopically by a transperitoneal approach and placed around the cavernous nerve. The leads were brought out to the subcutaneous space, where they were attached to stimulation receivers that could be activated by an external radiofrequency transmitter. An intracavernous pressure elevation indicative of successful stimulation was obtained acutely in five of eight cavernous nerves in the four acute-study dogs and in four of six nerves in the three chronic-study dogs. The implanted equipment associated with four of six cavernous nerves failed mechanically in the chronic-study animals, such that only two receiver-electrode sites were intact at the time of sacrifice 4 to 6 weeks later. Transmitter-driven stimulation of one of these two sets produced an intracavernous pressure rise above 100 cm H2O. We present this technique as part of the continuing evolution of laparoscopy as both a research and a clinical tool. The present use of the laparoscopically implantable nerve-stimulating electrode is a new animal research tool and a potential first step in the human application of the technology.

Animals↗

PubMed1994

Peyronie's disease: developments in diagnosis and treatment.

Advances in the field of diagnosis, management and therapy are highlighted in this review of Peyronies's disease. Much research is presently ongoing looking for etiologic agent to this process described more than 250 years ago. Use of new surgical techniques such as venous patch combined with less aggressive plaque management appear to be gaining favor among many leading urologists. A practical, algorithmic approach to the diagnosis and management is presented.

Journal Article↗

PubMed1993

A prostaglandin E1 dose-response study in man.

Because prostaglandin E1 causes erection by smooth muscle relaxation in a receptor-dependent manner, one would expect increasing dosages to cause a progressively greater response and that, at receptor saturation, further increases would not be beneficial. To test this hypothesis a single-blind, placebo-controlled study of increasing dosages of prostaglandin E1 injected intracavernously was done. In 16 men with vasculogenic impotence erections were monitored by the RigiScan device in real time for 2 hours after injection, and rigidity, tumescence and duration of erection were measured. Summary parameters to characterize erection with each dosage were developed: maximal rigidity, maximal rigidity sustained for 30 minutes and duration of greater than 60% rigidity. The dose-response curve was similar for all 3 parameters. The initial response to escalating doses of prostaglandin E1 from 2.5 to 20 micrograms. demonstrated a steep dose-dependent increase; at greater than 20 micrograms. a plateau was reached, indicating a nonlinear response. More than 80% of the patients attained the maximal response at doses of 20 micrograms. or less and less than 20% benefited from a further increase. Based on these results, the effects of prostaglandin E1 appear to be receptor-dependent and prostaglandin E1 monotherapy for impotence could be limited to 20 micrograms. or less, since larger amounts offer little additional benefit.

Alprostadil↗

PubMed1993

Combined cavernous compression device and arteriovenous-cavernous fistula: a chronic canine model.

In 5 dogs studied over a 3-month period, we evaluated the chronic effects of the combination of deep dorsal vein arterialization with implantation of an inflatable venous compression device. The device was placed around the proximal corpora cavernosa, sparing the left dorsal artery. A left-to-right, end-to-side dorsal artery-dorsal vein fistula was fashioned, and the right dorsal vein was anastomosed to the corpus cavernosum as an end-to-side venocorporeal window. From postoperative day 15, the device was activated twice a day for 3 months. Intracavernous pressure (bilateral) and left dorsal artery blood flow were monitored, and the patency of the anastomoses was evaluated by vascular clamping, arteriography, cavernosography and microscopic dissection. The device was well-tolerated, requiring no anesthesia during activation. (A sixth dog developed glanular hyperemia and priapism and was excluded from evaluation). With cuff inflation, the intracavernous pressure was significantly higher on the experimental side (range, 20 to 106 cm. H2O higher; p = 0.028), and arteriography demonstrated contrast flowing in the fistula and window in 3 of 4 dogs in which it was done. Both clamping and microscopic dissection of the specimen showed patency of the anastomoses in all 5 dogs. Histologic examination revealed maintenance of normal cavernous tissue histology.

Anastomosis, Surgical↗

PubMed1993

Drug-induced male sexual dysfunction. An update.

Impotence, defined as the consistent inability to maintain an erect penis of sufficient rigidity for sexual intercourse, has been estimated to affect 10 million American men. An age dependence has been shown to exist, with 25% of men over age 65 affected. A large body of clinical experience and published reports in the literature link many commonly prescribed drugs with sexual dysfunction. Drugs can affect sexual function at a variety of points such as inhibition of ejaculation or sedation/depression leading to reduced libido. Antihypertensive drugs have been most commonly associated with impotence. There have been reports of sexual dysfunction with almost all classes of antipsychotics, but little clinical investigation has been performed. Other drugs associated with sexual dysfunction include digoxin, clofibrate, cimetidine and various hormonal agents and antineoplastics. An important first step in approaching all impotent patients is the taking of a detailed medical, surgical, sexual and drug/substance abuse history. The least invasive form of therapy should be employed. Recent studies have shown intracavernous injections of alprostadil (prostaglandin E1) to be safe and effective for long term use. Vacuum constriction devices may also be of help. Better and more durable prostheses are now available should other treatment be unsuccessful.

Antihypertensive Agents↗