George S. Benson

A Quantitatively Controlled Method to Study Prospectively Interstitial Cystitis and Demonstrate the Efficacy of Pentosanpolysulfate

A randomized, prospective, double-blind, placebo-controlled study was conducted at 7 clinical centers on 148 patients. Patients received orally either 100 mg. pentosanpolysulfate (a synthetic polysaccharide) 3 times per day or a placebo. Of the patients on drug therapy 32% showed significant improvement compared to 16% of those on placebo (p = 0.01). This study provides a model to assess this disease quantitatively in a prospective manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0, 25, 50, 75 or 100%. Patients on drug therapy also experienced a significant decrease in pain and urgency (p = 0.04 and 0.01) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml. in voided volume than did placebo patients (p = 0.02). All adverse effects were minor, with 7 in the drug group and 10 in the placebo group. The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans.

Neuromorphology and Neuropharmacology of the Human Penis: AN IN VITRO STUDY

The neuromorphology and neuropharmacology of the human penis are only briefly described in literature. The present study was undertaken to define the adrenergic and cholinergic neuromorphology of the human corpus cavernosum (CC) and corpus spongiosum and to evaluate the in vitro response of the CC to pharmacologic stimulation. Human penile tissue was obtained from six transsexual patients undergoing penectomy. For morphologic study, the tissue was processed for (a) hematoxylin and eosin staining; (b) smooth muscle staining; (c) acetylcholinesterase localization; (d) glyoxylic acid histofluorescence; (e) electron microscopy; and (f) electron microscopy after glutaraldehyde dichromate fixation. In addition, strips of CC were placed in in vitro muscle chambers and tension changes recorded isometrically after stimulation with norepinephrine (NE) and acetylcholine. The CC contains abundant smooth muscle, numerous glyoxylic acidfluorescent (catecholaminergic) fibers and varicosities, and a scant distribution of acetylcholinesterase-positive fibers. Fewer of all these elements were present in the corpus spongiosum. No polsters were observed in the CC. Although glutaraldehyde-fixed controls exhibited no typical adrenergic vesicles (small, dense core, measuring 400-600 A in diameter), some small, strongly electron-dense vesicles were found in glutaraldehyde dichromate-fixed tissue and were thought to contain NE. A variety of other vesicles were also encountered. The addition of NE to the in vitro muscle chambers caused a dose-related contraction, which was blocked by pretreatment with phentolamine in all CC strips tested. Acetylcholine in high concentration produced minimal contraction in 2 of 24 strips. Our morphologic and pharmacologic data suggest that the sympathetic nervous system may affect erection by acting not only on the penile vasculature but also by direct action on the smooth muscle of the CC itself.

Autonomic innervation of the mammalian penis: a histochemical and physiological study.

The distribution of adrenergic and cholinergic nerves was studied in penile tissue from rat, rabbit, cat, monkey and man. Glyoxylic acid histofluorescence and acetylcholinesterase-positive fibers were found in all tissues examined, but histofluorescent, presumably adrenergic fibers predominated. In general, except in the rabbit, more nerve fibers of both types were found in the corpus cavernosum (CC) than in the corpus spongiosum/penile urethra (CS). The rabbit penis showed slightly more adrenergic fibers in the CC than in the CS and more cholinergic nerves in the CS than in the CC. The CC of the monkey demonstrated an alpha receptor mediated contractile response to norepinephrine (NE) stimulation and no response to acetylcholine (ACh) in anin vitro muscle bath.

Anatomical Localization and Some Pharmacological Effects of Vasoactive Intestinal Polypeptide in Human and Monkey Corpus Cavernosum

Vasoactive intestinal polypeptide is hypothesized to be a nonadrenergic, noncholinergic neurotransmitter important in the physiology of penile erection. To further explore this concept, anatomical localization of vasoactive intestinal polypeptide, in vitro muscle bath studies and in vivo injection experiments were undertaken in the monkey and man. Using immunohistochemical techniques vasoactive intestinal polypeptide was localized at the light microscopic level to nerves within the monkey and human penis. Ultrastructurally, a modified peroxidase-antiperoxidase technique was used to identify large vasoactive intestinal polypeptide-positive vesicles within peptidergic and cholinergic varicosities. In the in vitro muscle bath, the addition of 10(-7) M vasoactive intestinal polypeptide did not alter the baseline tension of strips of monkey and human corpus cavernosum. During contraction produced by norepinephrine stimulation, however, vasoactive intestinal polypeptide (10(-7) M) caused relaxation of the monkey (41 +/- 18 per cent, no. = 8) and human (23 +/- 8 per cent, no. = 5) corpus cavernosum. Intracorporal injection of vasoactive intestinal polypeptide (0.75 X 10(-9) to 3.75 X 10(-9) moles/kg.) had no effect on the monkey penis. Administration of vasoactive intestinal polypeptide (1.25 X 10(-9) to 2.5 X 10(-9) moles/kg.) into the internal iliac artery of the monkey, while having no effect on the flaccid penis, caused detumescence of the erect penis obtained by cavernous nerve stimulation (2-5 V, 40 Hz, 2 msec.). Although vasoactive intestinal polypeptide can be found within the nerves of the penis, its apparent in vitro and in vivo effects raise further questions concerning the role of this peptide in penile erection.

Autonomic innervation of the urogenital system: adrenergic and cholinergic elements

The major organs of the male urogenital (UG) system have been examined in various mammals, including man, using light and electron microscopic (EM) histochemical methods. For the light microscopic study, the urinary bladder, the vas deferens and the penis (corpora cavernosa and corpus spongiosum) were studied in the rat, cat, dog, monkey and man using a glyoxylic acid (GA) method modified for peripheral adrenergic nerve fibers, and a thiocholine method for acetylcholinesterase (AChE). Fine structural analysis was done on the vasa of rat, cat, monkey and man, and on the bladder and penis of cat, dog, monkey and man. Tissue was fixed in glutaraldehyde (GMO) as a control or in glutaraldehyde-dichromate (GDC) for the specific localization of norepinephrine (NE). All organs studied demonstrated numerous adrenergic nerve fibers throughout the muscular layers, in the connective tissue, and in the adventitia of most blood vessels. These fibers had a brilliant fluorescence when visualized with the GA method, and demonstrated many varicosities with small (400-600 A) and/or large (800-1200 A) granular vesicles in both control and GDC-fixed tissue examined with the EM. Evaluation of the vesicles with the analytical electron microscope (AEM) verified that those in the GDC-fixed tissue were chrome-positive, and, therefore, NE-containing. In the vas and penis, acetylcholinesterase(AChE)-positive nerve fibers were encountered less frequently at the light microscopic level than adrenergic fibers, and few typical cholinergic varicosities were seen in these organs with the EM. In the bladder, cholinergic nerves were seen with about the same frequency as adrenergic fibers in both light microscopic and EM preparations. Also observed frequently in each of the viscera were varicosities with large to very large (800-2000 A) granular vesicles of the kind presently hypothesized to be peptidergic or purinergic. Few varicosities of the type considered sensory, with large (800-1200 A) clear vesicles and numerous mitochondria, were observed in this tissue. Evidence from this study suggests that mammalian UG organs are innervated extensively by adrenergic nerves, and, excepting the bladder, have a limited cholinergic innervation; in the bladder, numerous fibers of each type can be found. In addition, another type of nerve fiber, perhaps peptidergic or purinergic, is found in large numbers in each of the organs studied and thus may represent a significant effector of autonomic regulation.

Voiding and erectile function after delayed one-stage repair of posterior urethral disruptions in 50 men with a fractured pelvis

We evaluated 50 men who suffered a total disruption of the posterior urethra in conjunction with a fractured pelvis. The urethral disruption was treated with immediate placement of a suprapubic cystostomy and delayed one-stage urethroplasty. Subsequently, 15 required at least one visual urethrotomy and three underwent one urethral dilatation. All 50 now have a patent urethra and 38 (76%) void normally and are continent. Five have an areflexic bladder secondary to the injury and intermittently catheterize themselves but are continent. Three patients have mild urge incontinence and three mild stress incontinence, not requiring treatment or protection. One patient with an open bladder neck has moderate stress incontinence which has responded to imipramine therapy. Impotence was present both preoperatively and postoperatively in 24 (48%) of the patients but by one year only 16 (32%) of them were still not having erections. Eighteen patients (36%) claim to have erections equal to their pre-injury quality. However, 16 (32%) of the patients, although potent and able to have intercourse, have less than optimal erections.

The Functional Approach to the Management of the Pediatric Neuropathic Bladder: A Clinical Study

A functional approach has been used in the management of the pediatric neuropathic bladder. Herein we report on our experience with incontinent children using pharmacologic manipulation with anticholinergic and sympathomimetic agents. Neuropharmacology and neuroanatomy as they apply to this approach are reviewed.

HIGH FLOW PRIAPISM ASSOCIATED WITH SICKLE CELL DISEASE

Priapism associated with sickle cell disease is classically described as a low flow state. We report 2 cases of high flow priapism associated with sickle cell disease. High flow priapism has previously been reported almost exclusively in patients with traumatic rupture of the cavernous artery. Neither of our patients had historical or radiographic findings consistent with injury to the penile vasculature. One patient was treated unsuccessfully with intracorporeal injection of methylene blue and 1 underwent successfully bilateral pudendal artery embolization. The pathophysiological mechanism(s) responsible for the production of high flow priapism in patients with sickle cell disease is not known.

Intraoperative decision-making in renal trauma surgery.

Surgery for renal trauma requires three intraoperative decisions: Should the kidney be explored? Is pedicle control necessary? What procedure should be performed? In 85 explorations for penetrating (66) and blunt (19) trauma, we found that penetrating injuries, active hemorrhage, or major tissue destruction are reasons for mandatory renal exploration. This resulted in 26 nephrectomies, 9 partial nephrectomies, and 4 major renorrhaphies. Forty-six patients underwent minor renorrhaphy or needless exploration without complications. Formal pedicle control was carried out 33 times (39%), but it was never necessary to control parenchymal hemorrhage. Unless a wound overlies the great vessels, perirenal hematomas can be safely entered laterally without prior pedicle control using manual pedicle or parenchymal control if needed.

Adrenergic innervation of the human bladder body.

AbstractAdrenergic nerve terminals were localized in the human bladder body by glyoxylic acid histofluorescence. No differences were observed between bladders of male and female subjects.