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Biomedical subjects

B von Heyden

Publications and source records attributed to B von Heyden.

At least 19 recordsLinked to original sources

[Intravesical therapy of interstitial cystitis].

Intravesically applied medications have the benefit of establishing high concentrations of a therapeutic agent at the intended target tissue along with a low risk for systemic side effects. Pentosanpolysulfate is frequently applied for this purpose and was shown to significantly reduce nycturia while frequency during the day remained unaffected in a controlled study. Heparin reduced nycturia in an open prospective protocol as well. For heparin the maximal onset of a therapeutic effect is often observed as late as 4-6 months after initiation of treatment. Heparin as well as pentosanpolysulfate cause practically no side effects. Dimethylsulfoxide (DMSO), when instilled intravesically, decreases symptoms up to 50-70% for an effective period of 1-2 months. An irritating but harmless side effect of DMSO is the development of a striking garlic-like odor. BCG improved symptoms in 10 of 15 patients after 8 months and in 8 of 15 patients after 24 months. No patient with an initial bladder capacity below 175 cc benefited from BCG instillations. Discomfort in the bladder region was noted as a frequent side effect. Instillations of clorpactin WCS 90 are painful and can thus only be applied under anesthesia. Success rates range between 50-70% and last for 6-12 months.

Administration, Intravesical↗

[Endourological surgical techniques in interstitial nephritis].

Endourological surgical procedures (transurethral resection and fulguration, Nd-YAG-laser application) for the treatment of interstitial cystitis (IC) have been evaluated only in a few studies. Theoretically, they could be the next step in a therapeutic concept after conservative measures have failed and before open surgery is performed as an ultima ratio. However, our review of the literature suggests that to date there is no scientific evidence to support endourological techniques in the treatment of IC.

Cystoscopy↗

In vitro electrostimulation-induced urethral relaxation in the guinea pig is blocked by prazosin.

The purpose of this study was to characterize the electrostimulation-induced relaxation in guinea pig urethral rings. From sacrificed male guinea pigs, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. The drop in baseline tension in response to electrical stimulation (rectangular pulses of 0.8-msec pulse duration, a frequency of 3, 5, 10, and 20 Hz, and 75-mA current) was measured in the presence of various pharmacologic agents. In urethral tissue precontracted with 10(-5) norepinephrine, a significant relaxation of 34.8% was found at 10 Hz. This relaxation was not affected by the addition of neuropeptide Y (NPY, 10(-8)-10(-6) M), 10(-6) M atropine, 10(-5) M alpha-beta-methylene-adenosine,5'-triphosphate (alpha-beta-methylene-ATP, a purinergic antagonist), and tolazoline (alpha2 antagonist, 10(-8)-10(-4) M). However, with the alpha1 antagonist prazosin (5 x 10(-8)-5 x 10(-7) M), no relaxation occurred. The tissue response was of neurogenic origin as it was blocked by 10(-7) M tetrodotoxin. Norepinephrine-precontracted urethral rings of male guinea pigs exhibit a relaxation response at 10 Hz that is alpha1-adrenergic, non-cholinergic, non-purinergic, and independent of NPY.

Adenosine Triphosphate↗

The latissimus dorsi bladder myoplasty to assist detrusor function.

The objective of this study was to evaluate whether an innervated skeletal muscle might augment detrusor function. In four dogs we performed the latissimus dorsi myoplasty, a transfer of the latissimus muscle as an innervated free flap wrapped around the bladder. Stimulation of the latissimus dorsi free flap initially achieved an average bladder pressure of 45.8 +/- 8.41 cm H2O, sufficient for partial evacuation. After 4 months the muscle generated a maximal pressure of 82 cm H2O, resulting in an evacuation of 27.7%. For selected patients, the latissimus dorsi bladder myoplasty may provide an alternative to intermittent catheterization in the future.

Animals↗

Neurotransmitters in the human urethral sphincter in the absence of voiding dysfunction.

The purpose of this study was to elucidate the neuroregulation of sphincteric relaxation by investigating the density of nerves containing acetylcholine, noradrenaline, neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) in the urethral sphincter in patients without a voiding disorder. The complete urethral sphincter (from the bladder neck to beyond the striated external sphincter) was excised from four male and four female adult cadavers and one male and one female fetus. In transverse paraffin or cryostat sections, the above transmitters were identified by histochemical methods. The striated sphincter was densely innervated by cholinergic nerves. Adrenergic nerves next to striated fibers were rare, but were present in all patients. NPY was seen rarely along striated fibers. In the smooth sphincteric component, noradrenaline-, acetylcholine-, NPY- and galanin-reactive nerves were observed frequently. Only functional studies can clarify the clinical implications of these results. Judging from NPY's scarcity in the striated sphincter no efferent function is anticipated. In the smooth component the frequent appearance of NPY, galanin and noradrenaline suggests a regulatory role for these transmitters.

Acetylcholine↗

Urethral relaxation after electrostimulation in the guinea pig is independent of nitric oxide.

PURPOSE: To investigate whether the relaxation of the striated urethral sphincter in guinea pigs is mediated by nitric oxide. MATERIALS AND METHODS: After sacrifice, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. Maximal isometric tension obtained at 1, 3, 10 and 25 Hz electrical stimulation (Tmax) for 5 to 30 sec was measured. RESULTS: Tmax at 25 Hz was not changed by pretreatment with 10(-4)M nitroprusside or 10(-4)M NG-nitro-L-arginine. In urethral tissue precontracted with 10(-4)M noradrenaline, a significant relaxation of 16-25% was found at 10 Hz. This relaxation could not be prevented by pretreatment with 10(-4)M NG-nitro-L-arginine and was not enhanced by the presence of 10(-3)M L-arginine. CONCLUSION: Noradrenaline-precontracted urethral rings of male guinea pigs exhibit a maximal relaxation at 10 Hz, which does not depend on nitric oxide.

Animals↗

The anatomy of the tunica albuginea in the normal penis and Peyronie's disease.

PURPOSE: We studied the fine architecture of the tunica albuginea of the penis. MATERIALS AND METHODS: The study included 6 human male cadavers and 10 surgical patients (5 with Peyronie's disease and 5 with normal penile anatomy). RESULTS: The tunica albuginea of the corpora cavernosa is a bi-layered structure with multiple sub layers. Inner layer bundles support and contain the cavernous tissue and are oriented circularly. Radiating from this layer are intracavernous pillars acting as struts, which augment the septum and provide essential support to the erectile tissue. Outer layer bundles are oriented longitudinally. These fibers extend from the glans penis to the proximal crura, where they insert into the inferior pubic ramus. There are no outer layer fibers between the 5 and 7 o'clock positions. Elastic fibers normally form an irregularly latticed network on which collagen fibers rest. In Peyronie's disease the well ordered appearance of the collagen layers is lost: excessive deposits of collagen, disordered elastic fibers and fibrin are found within the region of the plaque. CONCLUSIONS: The normal 3-dimensional structure of the tunica affords great flexibility, rigidity and tissue strength to the penis, which are lost consequent to structural changes in Peyronie's disease.

Humans↗

Intracavernous injection of linsidomine chlorhydrate in monkeys: lack of toxic effect with long-term use.

OBJECTIVE: We sought to investigate whether linsidomine chlorhydrate (SIN1, the active metabolite of molsidomine and a nitric oxide donor) has a toxic effect when used chronically for the treatment of impotence. METHODS: We gave 50 intracavernous injection of 1.5 mg SIN1 over 25 weeks to each of 5 monkeys. RESULTS: Four monkeys consistently responded with erections of sufficient rigidity and duration (mean 47.5 +/- 3.3 min), and none of the five evidenced histopathologic changes of the cavernous tissue. CONCLUSION: SIN1 appears to be a safe option for the pharmacotherapy of erectile dysfunction.

Animals↗

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↗

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↗

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↗

Anatomy and strength of the tunica albuginea: its relevance to penile prosthesis extrusion.

In 7 male cadavers the anatomical structure, thickness and tensile strength of the tunica albuginea of the penis, measured at specific locations, were determined. The tunica is composed of inner circular and outer longitudinal layers made up of collagen bundles. The outer layer appears to determine, to a large extent, the variation in thickness and strength of the tunica. The ventral groove (found between the 5 and 7 o'clock positions), which houses the corpus spongiosum, lacks outer bundles and appears vulnerable to perforation. The thickness of the tunica measured at the 7, 9 and 11 o'clock positions was 0.8 +/- 0.1 mm, 1.2 +/- 0.2 mm and 2.2 +/- 0.4 mm, respectively. Differences in the thickness of the tunica at specific locations were statistically significant (all p < or = 0.018). Symmetrical measurements were nearly identical in a mirror image arrangement (3, 5 and 1 at the 9, 7 and 11 o'clock positions, respectively). The stress on the tunica at penetration (breaking point pressure) measured at the 7, 9 and 11 o'clock positions was 1.6 +/- 0.2 x 10(7) N/m.2, 3.0 +/- 0.3 x 10(7) N/m2 and 4.5 +/- 0.5 x 10(7) N/m.2, respectively. The strength and thickness of the tunica correlated in a statistically significant manner with location (r = 0.911 and p = 0.0001). The most vulnerable area is on the ventral aspect (which lacks the longitudinally directed outer layer bundles), where most prostheses tend to extrude. This finding supports our belief that prosthesis extrusion often has an anatomical basis and is not merely a phenomenon caused by infection or compression.

Biomechanical Phenomena↗

The distribution of elastic fibrous elements within the human penis.

OBJECTIVE: To determine the distribution of elastic fibres in the tunica albuginea and the erectile tissue of the penis. MATERIALS AND METHODS: Samples of tunica albuginea or penile erectile tissue were taken from seven cadavers and five patients undergoing surgery. Light and electron microscopy were performed. RESULTS: There were two anatomical regions in which elastic fibres were seen rarely: the proximal crus and the distal tunica. In the rest of the corpora cavernosa where the tunica was more compliant, the elastic fibres were in relative abundance. In the corpus spongiosum, abundant irregularly oriented elastic fibres were present; the densest elastic network was found in the glans penis and was composed of coarse elastic fibres. A perisinusoidal fibroelastic shell was seen in the glans, which was probably an extension of Buck's fascia. The elastic components within the sinusoids (cavernosal, spongiosal, and glanular) were similar but finer than the elastic lamellae in the penile arterial wall. CONCLUSION: The elastic fibres were unevenly distributed, often forming an irregular network on which the collagen component rested. Elastic fibres were more abundant in the corpus spongiosum, around the blood vessels and surrounding the sinusoid of the corpus cavernosum.

Collagen↗

Can a venous patch graft be a substitute for the tunica albuginea of the penis?

We describe our experience with plaque excision and placement of a venous patch graft. Sprague Dawley rats (n = 20) underwent excision of a wedge of tunica albuginea with the defect covered by a segment of detubularized femoral vein, endothelial side towards the cavernous tissue. Erectile function, as determined by the rise in intracavernous pressure with cavernous nerve stimulation (mean 54.0 +/- 4.2 cm. H2O), was equal to that in a group of 10 intact age-matched controls (mean 46.9 +/- 3.37 cm. H2O). Penile cross-sections stained with Hart's elastic fiber stain or Trichrome stain revealed only minimal fibrosis in the region of the patch. In 3 dogs, a wedge of tunica was removed, and the defect was covered with a segment of detubularized deep dorsal vein. When sacrificed at 3 months, all animals had retained their erectile function with histologic evidence of minimal fibrosis. On the basis of histologic and functional data, the venous patch appears to be a reasonable alternative substance to those in common use.

Animals↗

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↗