Biomedical subjects

M C Truss

Publications and source records attributed to M C Truss.

61 records · Page 4Linked to original sources

PubMed1995

Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro.

OBJECTIVES: This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation. METHODS: PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips. RESULTS: Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%. CONCLUSIONS: Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Prognostic factors for the postoperative outcome of penile venous surgery for venogenic erectile dysfunction.

Since penile venous surgery is usually associated with a poor postoperative outcome, a study was done to evaluate possible prognostic factors for this procedure. A total of 77 patients with erectile dysfunction underwent ligation of all dorsal penile veins and resection of the deep dorsal penile vein for venous incompetence. In all patients a comprehensive evaluation was done preoperatively. All patients did not respond to pharmacotherapy and had a venous leak. After a followup of 6 months, patients were classified as having full spontaneous erections, failure and response to pharmacotherapy. Of the 77 patients 31 (40.3%) had full spontaneous erections, 8 (10.3%) were currently responding to pharmacotherapy and 38 (49.4%) failed. The maintenance flow was 75 +/- 45 ml. per minute in the group with spontaneous erections and 103 +/- 60 ml. per minute in the failure group (p = 0.20). Mean patient age was 49.8 +/- 11.7 and 49.1 +/- 10.2 years, respectively (p = 0.23). Of the 41 patients wih normal single potential analysis of cavernous electrical activity 28 had full erections postoperatively, 5 responded to pharmacotherapy and 8 failed, compared to 3, 3 and 30, respectively, of the 36 patients with abnormal single potential analysis of cavernous electrical activity. After a mean followup of 21 months (range 6 to 47 months), 4 patients with full erections at 6 months postoperatively currently require intracavernous pharmacotherapy. Our results indicate that single potential analysis of cavernous electrical activity seems to be an important prognostic factor for the postoperative outcome of penile venous surgery for venogenic impotence.

Adult↗

PubMed1994

Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction.

OBJECTIVES: Recently, nitric oxide was shown to be a mediator of penile erection in men and the nitric oxide donor linsidomine chlorhydrate (SIN-1) was introduced as a novel treatment option in patients with erectile dysfunction. We now present our follow-up results with the intracavernous application of SIN-1. METHODS: One hundred thirteen patients with erectile dysfunction of various etiologies and 10 normal control subjects underwent intracavernous pharmacotesting with 1 mg SIN-1. Of the 113 patients, 71 (62.8%) underwent additional pharmacotesting with a mixture of papaverine (15 mg/mL) and phentolamine (0.5 mg/mL) (P/P). Forty-eight responders to SIN-1 were enrolled in an autoinjection program with this substance. RESULTS: All normal control subjects had full rigid erections lasting 40 to 70 minutes. Of 113 patients, 78 (69%) had responses sufficient for intercourse with SIN-1, and the other 35 patients (31%) demonstrated inadequate responses. All 44 responders to SIN-1 who also received P/P had erections sufficient for intercourse with P/P in doses of 0.25 to 2 mL (mean, 0.6 +/- 0.3 mL). Six patients (13.6%) had prolonged erections with minimal to moderate doses of P/P. From the total of 27 patients who had erections insufficient for intercourse with SIN-1, 20 (74.1%) had good responses with 0.25 to 2.0 mL P/P (mean, 1.5 +/- 0.5 mL). One patient (4%) had a prolonged erection with 1.0 mL P/P: After 10 to 150 injections/patient (total of 1160 injections; mean, 24.1 injections), no significant side effects were noted with SIN-1. CONCLUSIONS: Our data suggest that intracavernous SIN-1 is safe and efficacious in the majority of patients with erectile dysfunction; however, it has a lower smooth muscle relaxing effect than a combination of P/P. The absence of severe side effects, including priapisms, may be explained by the use of a physiologic pathway for induction of the erectile response and the rapid intracavernous decomposition of SIN-1.

Adult↗

PubMed1994

Intracavernous calcitonin gene-related peptide plus prostaglandin E1: possible alternative to penile implants in selected patients.

The implantation of a penile prosthesis is still the ultima ratio for patients with erectile dysfunction who fail other treatment options such as pharmacotherapy and penile venous surgery. Despite mostly favorable results regarding restoration of erectile capacity, penile allografts are often not accepted for various reasons. Therefore, pharmacotesting with a mixture of calcitonin gene-related peptide and prostaglandin E1 (CGRP/PGE1) was offered to different selected patients populations: 28 patients with erectile dysfunction and venous leakage who failed penile venous surgery, 28 patients with erectile dysfunction and venous leakage (who refused penile venous surgery) and 12 patients without venous leakage, but poor response to maximum doses of papaverine/phentolamine, received 5 micrograms CGRP plus 10 micrograms PGE1. Erections sufficient for intercourse were noted in 19/28 (67.9%), 20/28 (71.4%) and 11/12 (91.7%) patients, respectively. Our data show that a combination of CGRP and PGE1 may be an alternative to penile implants in selected patients.

Alprostadil↗

PubMed1993

Single potential analysis of cavernous electrical activity. Four years' experience in more than 500 patients with erectile dysfunction.

Since the recent introduction of cavernous electromyography by Gerstenberg and Wagner, a new too for the study of erectile dysfunction in man is available. The refinement of this method, single potential analysis of cavernous electrical activity (SPACE), offers a straightforward approach to the diagnosis of cavernous autonomic neuropathy and smooth muscle myopathy by minimal invasive means. SPACE was done in more than 500 consecutive patients with erectile dysfunction and in 85 normal control subjects. With increasing experience the methodology was refined with respect to the used hardware as well as cut-off frequencies. In normal control subjects, SPACE showed a reproducible regular activity with potentials of low frequency and electrical silence inbetween. The potentials were synchronous throughout the cavernous bodies. In patients with peripheral autonomic denervation, asynchronous potentials with higher frequencies and irregular shape were found. Normal and abnormal potentials were found in patients with upper spinal cord lesions. Recordings obtained with surface electrodes showed similar characteristics when compared with recordings obtained with needle electrodes. Recent studies show that SPACE provides independent information about the autonomic and myogenic intactness of the cavernous tissue. Currently, a computerized expert system and a graded classification for easier interpretation is being developed with first results. We conclude that cavernous electrical activity can be recorded. SPACE is a reproducible diagnostic tool for erectile dysfunction.

Action Potentials↗

PubMed1993

Single potential analysis of cavernous electrical activity (SPACE). Experiences, limitations and perspectives.

Cavernous electromyography was first introduced by Wagner and Gerstenberg in 1989. The authors developed a refined method of cavernous electromyography by means of single potential analysis in introduced this method into clinical Urology as a diagnostic procedure for the evaluation of patients presenting with erectile dysfunction. To date, our experience with single potential analysis of cavernous electrical activity (SPACE) includes more than 500 patients with erectile dysfunction of various etiologies and 92 normal control subjects. Several technical modifications and refinements have been adopted during the last 4 years. In normal control subjects, SPACE shows a regular pattern of activity with long phases of electrical silence at the usual amplification interrupted by synchronous low frequency, high amplitude potentials. In patients with disruption of the peripheral autonomic supply, typical asynchronous potentials with higher frequencies and irregular shape are observed. In complete spinal cord lesions, abnormal as well as normal electrical activity is found. In patients with a long history of insulin-dependent diabetes and presumably cavernous smooth muscle degeneration, SPACE recordings show irregular potentials with low amplitudes and slow depolarization speed. Synchronization of electrical activity is usually absent. Recent studies on patients with venous leakage show that SPACE provides independent clinical information about the cavernous smooth musculature. The recording of cavernous electrical activity is possible and reproductible. In the future, a new software for one-line date processing, storage and interpretation of SPACE signals will be available.

Action Potentials↗

PubMedDate not supplied

General anesthesia for ureteral measurements in the rabbit.

Literature search and in vitro studies on ureteral function in humans and rabbits have proven that the rabbit is a suitable animal model for the investigation of the effect of smooth muscle relaxing substances on the ureter. One of the main problems encountered was to find an appropriate anesthetic protocol for this animal model. Application of barbiturates as a monotherapy proved to be unsuitable to allow painfree preparation of the abdomen. Intravenous (iv) anesthesia consisting of ketamine-HCl/xylazine-HCl could not be considered due to interference with ureteral smooth muscle tone. Intravenous administration of ketamine-HCl induced immediate ureteral contractions with increased frequency of ureteral activity. Xylazine-hydrochloride, a mixed alpha 2-, alpha 1-adrenoceptor agonist inhibits the increase in synthesis of 3'5'-cAMP. Since the test substances used are phosphodiesterase-IV-inhibitors (rolipram and its two enantiomers), which increase 3'5'-cAMP, this type of anesthesia would interfere with the pharmacological effect to be investigated. General anesthesia using a combination of nitrous oxide (2 l/min) and oxygen (1 l/min) and a very small amount (2 mg/kg b.w.) of pentobarbital i.v. every 30 minutes, was found to be the most suitable form of anesthesia. It resulted in much more stable circulatory conditions, sufficient depth of anesthesia and the possibility to test muscle relaxing substances (PDE-IV-inhibitor) without any influence from anesthesia on their efficacy.

Anesthesia, General↗