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Biomedical subjects

H H Knispel

Publications and source records attributed to H H Knispel.

At least 37 records · Page 2Linked to original sources

Nitroxergic innervation of the human ureterovesical junction.

Nitric oxide synthase (NOS) immunohistochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were used to investigate the distribution of nitroxergic, i.e., nitric oxide-synthesizing, neuronal perikarya and processes in the human ureterovesical junction (UVJ). Tissue specimens obtained from two cadaver kidney donors and two patients undergoing radical cystectomy for bladder cancer were examined. Clusters of NOS-immunoreactive neurons were localized in extramural ureterovesical ganglia. NOS-containing nerve fibers traveled within large extramural nerve trunks and marched among smooth muscle bundles. Extramural and intramural blood vessels were encircled by varicose NOS-positive axonal processes. The distribution of NOS immunoreactivity paralleled the staining pattern for NADPH-d activity. Urothelium stained strongly for NADPH-d activity but showed no NOS immunolabeling. Specimens from all four patients investigated showed similar staining patterns. Our results suggest that nitric oxide, a potent smooth-muscle-relaxing neurotransmitter in the autonomic nervous system, plays a physiologic role in opening the human UVJ.

Adult↗

Nitric oxide donor, linsidomine chlorhydrate (SIN-1), in the diagnosis and treatment of erectile dysfunction: critical appraisal and review of the literature.

Recent experimental work has demonstrated that nitric oxide (NO) is the neutrotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have come to conflicting results ranging from highest praise to complete dismissal. We reviewed all published studies on the use of SIN-1 for intracorporeal injection in erectile failure including our own. To this date, 3 groups published their data. Only the uncontrolled data from Hannover claim good results. The controlled data from Hamburg and Berlin on patients with erectile failure due to venous leakage, to a mixed aetiology in a double-blind fashion and to mixed aetiology with drug increase (1 mg versus 2 mg of SIN-1) showed a significantly worse performance of SIN-1 compared to the standard drug for penile injection, prostaglandin E1. We conclude that there is no place for linsidomine chlorhydrate in either the diagnosis or the treatment of erectile dysfunction.

Animals↗

Evaluation of penile arteries with color-coded duplex sonography: prevalence and possible therapeutic implications of connections between dorsal and cavernous arteries in impotent men.

Penile revascularization for cases of arteriogenic impotence is based on the assumption of hemodynamically relevant connections between the dorsal penile and cavernous arteries. In 325 clinically impotent patients color-coded duplex sonography was performed with the penis flaccid and tumescent after intracavernous injection of 10 micrograms prostaglandin E1. We measured peak flow velocity, end diastolic flow velocity and resistance in the dorsal arteries, deep cavernous arteries and connections perforating the tunica albuginea between the 2 systems. Of our patients 14% had at least 1 such anastomosis with a peak flow velocity exceeding 25 cm. per second after stimulation. Peak flow velocities less than 20 cm. per second were noted only in arteriogenically impotent patients, while those exceeding 25 cm. per second without later rigid erection occurred only in patients with venous occlusive dysfunction and end diastolic flow velocity exceeded 5 cm. per second. We conclude that penile revascularization should be contemplated only if hemodynamically relevant connections are detected, peak flow velocity in the cavernous arteries is less than 20 cm. per second and end diastolic flow velocity is less than 5 cm. per second.

Alprostadil↗

Laparoscopic pelvic lymphadenectomy in prostatic cancer: an analysis of seventy consecutive cases.

From July 1992 to April 1994, 70 patients with prostatic cancer underwent laparoscopic pelvic lymph-node dissection (LPLD) before retropubic radical prostatectomy or afterloading therapy in our clinic. After an initial learning phase, the accuracy of LPLD was excellent, with only 3.0% residual nodes and no false-negative results due to LPLD. The rate of severe complications was 5.7% (4/70). No transfusions were required due to LPLD. If patients with positive nodes (D1) were excluded from local therapy, the benefits of LPLD were estimated as 12 patients with positive nodes avoiding open surgery (17.1%); 15 patients undergoing afterloading therapy and avoiding open surgery (21.4%); 1 patient with high preoperative prostate-specific antigen having a chance of surgical cure (1.4%) - a total of 28 of 70 patients (40.0%). We conclude that, depending on the therapeutic concept applied, LPLD is beneficial for patients with prostatic cancer, it opens the door for other curative procedures like after-loading therapy, and reappraisal of perineal prostatectomy.

Adult↗

Efficacy of linsidomine chlorhydrate, a direct nitric oxide donor, in the treatment of human erectile dysfunction: results of a double-blind cross over trial.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor SIN-1 (linsidomine chlorhydrate) in patients with erectile dysfunction have come to conflicting results. We have performed a double-blind cross over trial in 40 patients with erectile dysfunction of mixed etiology comparing SIN-1, SIN-1 plus the alpha-blocker Urapidil, and prostaglandin E1 (PGE1) in order to determine the effectiveness of SIN-1. PGE1 achieved the best response, the combination of SIN-1 and Urapidil performed slightly, statistically insignificantly poorer with significantly increased side effects. SIN-1 alone performed statistically significantly (p < 0.0068) worse. SIN-1 is not a useful alternative to PGE1. The combination of SIN-1 and Urapidil performs equally as good as PGE1 but cannot be recommended due to intolerable side effects.

Adult↗

Prostaglandin E1 versus linsidomine chlorhydrate in erectile dysfunction.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO donor linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have had conflicting results. We performed a single-blind cross-over trial in 20 patients with erectile dysfunction of mixed etiology comparing prostaglandin E1 (PGE1) to SIN-1 at two different dosages (1 and 2 mg, respectively) in order to determine the effectiveness of SIN-1. PGE1 always achieved the best response, SIN-1 performed statistically significantly poorer irrespective of the dosage used. There were only a few side effects with no significant difference. SIN-1 is not a useful alternative to PGE1 in the treatment of erectile dysfunction.

Adult↗

Effects of papaverine and prostaglandin E1 on corpus cavernosum smooth muscle of arteriogenically and diabetically impotent men.

Relaxant effect of prostaglandin E1 (PGE1) and papaverine (PAP) were measured in strips of corpus cavernosum smooth muscle taken from a healthy control group of men (A; n = 5), from arteriogenically impotent men (B; n = 6) and from additionally diabetic impotent men (C; n = 5) with venous leakage. Maximal relaxant effect was achieved with PAP at a mean of 10(-4) mol/l and PGE1 at a mean of 5.8 x 10(-6) mol/l. PAP induced complete relaxation in all strips. There was no difference in relaxant effects between groups. Relaxant effect was less pronounced and depended significantly on etiology: phenylephrine-induced tension was reduced by 76 +/- 8% (A), 54 +/- 14% (B) and 23 +/- 18% (C), respectively. In conclusion, our data suggest degradation of PGE1 receptors depending on the cause of erectile dysfunction. Furthermore, relaxant capacity of cavernous smooth muscle per se seems not to be impaired in impotence. Therefore, pathophysiology of venous leakage cannot sufficiently be explained by a lack of relaxation.

Alprostadil↗

Acetylsalicylic acid inhibition of n-butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats.

We examined the effect of acetylsalicylic acid (ASA) on n-butyl-(4-hydroxybutyl)nitrosamine (BHBN)-induced bladder carcinogenesis in male Wistar rats. Of 29 rats that received 0.05% BHBN in their drinking water for 9 weeks, 8 developed bladder cancer. Only 1 out of 29 rats that received 0.1% ASA in their diet for 20 weeks, including the period of BHBN consumption, developed a tumor. That difference is statistically significant. Bladder weight was significantly higher in rats given BHBN than in controls and in rats given both BHBN and ASA. We conclude that ASA inhibits BHBN-induced bladder carcinogenesis.

Animals↗

Effect of nitric oxide-donor, linsidomine chlorhydrate, in treatment of human erectile dysfunction caused by venous leakage.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. We studied the effect of a direct NO-donor, linsidomine chlorhydrate (SIN-1), in 30 patients with venous leakage confirmed by dynamic pharmacocavernosography and pharmacocavernosometry that was refractory to prostaglandin E1 (PGE1) under the assumption that the more physiologic approach might give better results. In all 30 patients, response to SIN-1 was no better, and in 22 cases it was less than the response to PGE1. No systemic or local side effects of SIN-1 were observed. SIN-1 is not superior to PGE1 in the treatment of erectile dysfunction caused by venous leakage, and failure of NO-mediated smooth muscle relaxation does not play a part in the entity, "venous leakage."

Adult↗

Evaluation of vasculogenic impotence by monitoring of cavernous oxygen tension.

Color coded duplex sonography, regarded as the gold standard in penile vascular evaluation, does not yield data on cavernous oxygenation itself. In addition to using color coded duplex sonography to measure peak flow velocity in cavernous arteries after injection of 20 micrograms. prostaglandin E1 in 34 unselected patients with impotence, we monitored cavernous oxygen tension with oxygen-sensitive Eppendorf needle electrode. During flaccidity the mean cavernous oxygen tension of 38 mm. Hg increased to 61 mm. Hg after injection of prostaglandin E1. Peak flow shown with color coded duplex sonography and maximal oxygen tension correlated well in 24 men (71%). However, in 10 men (29%) normal peak flow did not result in a cavernous oxygen tension of greater than 65 mm. Hg, so this might have been isolated cavernous perfusion defects. In contrast, there was no case of impaired arterial inflow and high oxygen tension. Monitoring of cavernous oxygen tension allows for characterization of patients with cavernous perfusion deficiency. This new and simple diagnostic method might help to improve diagnosis and followup after penile vascular surgery. However, more data on patients and controls will be required to define normal ranges.

Alprostadil↗

[Endoscopic lithotripsy with pneumatic shockwave (Swiss Lithoclast) using a mini-ureteroscope].

We performed endoscopic lithotripsy for 23 urinary stones (21 ureteral and 2 bladder stones) with a pneumatic shockwave unit (Swiss Lithoclast; EMS, Angiomed), for the first time applying the probe through the tangential working channel of a semirigid 6.9-Fr ureteroscope (Circon, ACMI). Disintegration was successful in all stones (5-24 mm). Immediately after treatment, the 2 patients with bladder calculi and 10 of the patients with ureteral stones (47.6%) were stone free, while another 5 had residual fragments < 3 mm. Migration of fragments in 4 patients (19%) led to subsequent extracorporeal shock wave lithotripsy. There were no ureteral perforations in this series. Routine application of double-J stents avoided any serious postoperative complications. Endoscopic lithotripsy with the pneumatic shockwave unit was shown to be highly effective regardless of stone composition. The ltihotripsy probe is easily applied through mini-ureteroscopes.

Adolescent↗

Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle.

We investigated in vitro the relaxant effect of exogenous acetylcholine (ACh) and electric-field stimulation (EFS) on rabbit and human corpus cavernosum smooth muscle strips (CC) precontracted with phenylephrine. The effects of EFS and ACh were monitored alone, after muscarinic receptor blockade and after inhibition of nitric oxide (NO) formation with L-N-nitro-arginine (L-NOARG). In rabbit and human CC, both atropine and L-NOARG abolished the relaxant effects of ACh. The relaxant effects of EFS, however, were only slightly reduced by atropine to 97.5 +/- 17.5% in human CC and to 89.0 +/- 6.1% in rabbit CC. L-NOARG further reduced the EFS effects to 0.8 +/- 1.7% in human CC and to 16.2 +/- 8.7% in rabbit CC. In strips obtained from impotent patients with diabetes mellitus, the relaxant effects appeared to be significantly less than in strips from nondiabetic impotent men. Tetrodotoxin blocked the relaxant EFS effects in human and rabbit strips completely. The data indicate the important role of NO in cholinergically induced relaxation of cavernous smooth muscle in rabbits and humans. Our findings support the idea of NO as the nonadrenergic noncholinergic neurotransmitter in penile erection in both species. Rabbit erectile tissue might serve as an in vitro animal model for further investigation.

Acetylcholine↗

Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation.

We investigated the relaxant effect of electric field stimulation (EFS) on rabbit cavernous smooth muscle strips in vitro precontracted by phenylephrine. Effects of EFS were monitored alone, and following muscarinic receptor blockade, and inhibition of nitric oxide (NO) formation by L-N-monomethylarginine (L-NMMA) or by L-N-nitroarginine (L-NOARG). Atropine only slightly reduced the relaxant effect of EFS to 89.0 +/- 6.1 percent. Additional application of L-NMMA further reduced the relaxant effect to 37.3 +/- 15.3 percent. Substitution of L-NOARG for L-NMMA led to a more pronounced inhibition of relaxant effects to 16.2 +/- 8.7 percent. The results indicate that neurogenically induced relaxation of rabbit cavernous smooth muscle is mediated mainly by NO formation and argue against a substantial role of relaxing peptidergic neurotransmitters, such as vasoactive intestinal polypeptide and calcitonin-gene-related peptide, in penile erection.

Animals↗

Influence of cause on choice of therapy in 174 patients with erectile dysfunction.

In 174 impotent patients consistent application of modern diagnostic methods, including dynamic color duplex sonography, pharmacocavernosography, nocturnal penile tumescence monitoring and psychological exploration, led to invasive therapy in 38 and to self-injection therapy in 76. Analysis of patients who received penile implants and those who performed self-injection did not show an important effect of etiology of impotence on the choice of treatment. Therefore, if penile vascular surgery is excluded, diagnostic procedures can be limited to a simplified goal-directed panel. Once psychogenic impotence is excluded through nocturnal penile tumescence monitoring, application of vasoactive drugs serves only to select patients to be considered for self-injection therapy. Implant surgery will be reserved for patients who fail to respond to any drug applied.

Adult↗

Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls.

The use of color-coded duplex sonography of the cavernous arteries in the assessment of arteriogenic impotence was evaluated in 70 consecutive men referred for erectile dysfunction. Controls were 16 of the men with an unequivocal nocturnal penile tumescence and rigidity. After intracavernous injection of prostaglandin E1, peak flow velocity was 26.8 +/- 12.5 cm/s in patients and 37.2 +/- 13.0 cm/s in controls (p less than 0.05). 50% of the patients, but none of the controls, had peak flow velocities of less than 20 cm/s in at least 1 cavernous artery. However, within the range of 20-40 cm/s, there was marked overlap between groups. The mean flow velocity and resistance index did not improve the discriminative value of peak flow velocity. Peak flow velocity after intracavernous injection of vasoactive drug enables the discrimination between impotent patients and controls. In a single patient, however, particularly one with a flow velocity of 20-40 cm/s, definition of arteriogenic impotence remains difficult.

Alprostadil↗

Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous smooth muscle.

Externally applied acetylcholine (ACh) in human corpus cavernosum has been shown to cause endothelium-dependent smooth muscle relaxation. Changes in isometric tension in rabbit cavernous smooth muscle strips mounted in organ bath chambers were monitored in the presence of blocking agents. Nitric oxide (NO) is known as an endothelium-derived relaxation factor (EDRF). Addition of specific inhibitors of nitric oxide synthesis, such as L-n-monomethyl arginine (L-NMMA) at 5 x 10(-4) mol/l.. or L-n-nitro arginine (L-NOARG) at 2 x 10(-4) mol/l. to strips precontracted with phenylephrine (PE) at 3.16 x 10(-6) mol/l. led to significant increases in tension. In the presence of L-NMMA or L-NOARG, relaxing effects of ACh at 10(-8)-3.16 x 10(-5) mol/l. mediated by muscarinic receptors were almost completely abolished. These data indicate that rabbit cavernous smooth muscle is under the control of basal NO release. They constitute strong evidence that cholinergically induced endothelial formation of NO plays a crucial role in relaxing cavernous smooth muscle.

Acetylcholine↗

Penile venous surgery in impotence: results in highly selected cases.

Currently, indications for penile venous surgery are dynamic pharmacocavernosographic findings in impotent patients who fail to respond to intracorporeal application of vasoactive substances and who demonstrate unimpaired arterial perfusion. We used pharmacocavernosometry to measure penile intracorporeal maintenance flow rate in 48 impotent men: 20 had maintenance flow rates higher than 30 ml/min, 12 of the 20 had leakage mainly via Santorini's plexus. In 7 of this 12, venous ligation procedures were initially successful, and in 6 of them erectile function returned. After a mean follow-up, seven of the 12 eventually had to be treated with penile implants. Another 4 used self-injection of prostaglandin E1; only 1 patient reported spontaneous erections sufficient for intercourse. Poor long-term results of surgery and recent data on active mechanisms in venous outflow restriction raise doubts as to whether penile venous surgery can ever cure so-called venous incompetence.

Adult↗