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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

At least 145 records · Page 8Linked to original sources

Single potential analysis of cavernous electrical activity.

Recording of cavernous electric activity was performed in 178 patients with erectile dysfunction and in 37 normal patients. In 34/37 normal patients, potentials of a uniform shape were recorded during flaccidity: At cut-off frequencies of 0.5-500 Hz, the length was 8-18 (mean 12.8, SD 2.8), the amplitude 250-750 (mean 444, SD 109) microV, and the polyphasity 8-22 (mean 13.8, SD 3.3). In impotent patients with upper motor neuron lesions or peripheral lesions, specific types of potentials were observed. In 11/14 impotent patients with insulin-dependent diabetes for over 20 years and clinical findings of cavernous myopathy, potentials showed low amplitude, irregular shape, and slow depolarizations. In 51% of the consecutive impotent patients, abnormal findings of cavernous electric activity were recorded. Our clinical study suggests that single potential analysis of cavernous electric activity (SPACE) may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.

Action Potentials↗

In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a.

Samples of 38 human renal cell carcinomas (RCC) were subjected to routine histopathological examination but also to in vitro sensitivity testing with mitomycin C, vinblastine and interferon Alpha-2a at various concentrations corresponding to serum titers recommended to be effective in vivo, employing a monolayer assay. Extending earlier in vitro studies, both tumor cell kill rates (TCKR) and proliferation rates (PR) were assessed. Following in vitro preparation the tumor cell cultures were simultaneously exposed to the anticancer drugs listed above. The proliferation rates were determined immunocytochemically using the monoclonal antibody Ki-67. Nine (23.7%) of the tumors investigated revealed temporary and limited response with respect to either TCKR or PR. Improvement of this percentage could only be obtained by increasing drug concentration to titers with toxicity intolerable for in vivo administration. The in vivo data presented correspond to clinical temporary and limited remissions in patients with metastatic RCC ranging up to 25%.

Antineoplastic Combined Chemotherapy Protocols↗

The sympathetic role as an antagonist of erection.

The effects of the lumbar and pelvic sympathetic system on penile erection were studied in a canine model. Erection was induced by cavernous nerve stimulation and detumescence by sympathetic trunk stimulation. Erection induced by cavernous nerve stimulation normally subsides slowly. After discontinuation of electrical stimulation the intracavernous pressure drops within a mean of 291 s to 50% and after a mean of 372 s to 10% of the highest level. However, stimulation of the sympathetic trunk at the level of L4-S1 applied directly after discontinuation of cavernous nerve stimulation accelerated this drop of intracavernous pressure significantly: to 50% after a mean of 19 s and to 10% after a mean of 36 s. If stimulation of the sympathetic trunk was initiated 20 s before cavernous nerve stimulation, the pressure rise was aborted completely. Neurostimulation of the hypogastric nerves alone or in combination with cavernous nerve stimulation did not change the intracavernous pressure. These results were not altered after neurotomy of the pudendal or hypogastric nerves. The main pathway of the fibers from the sympathetic trunk to the penis seems to run via the pelvic plexus. The stimulation voltage and frequency to induce erection or detumescence were equivalent. Our results suggest that an elevated central sympathetic tone may be one of the causes of psychogenic impotence.

Animals↗

Sympathetic inhibition of papaverine induced erection.

We studied the effect of neurostimulation of the lumbar sympathetic trunks on papaverine-induced penile erection in dogs and monkeys. The mean of 124 cm. H2O intracavernous pressure after papaverine injection was reduced under sympathetic trunk stimulation to 40.6 cm. H2O within a mean of 39 sec. In addition the flow of the internal pudendal artery was reduced indicating a decrease of the inflow to the penis. After the sympathetic stimulation was terminated, the intracavernous pressure increased again to the same level as before. This pressure recovery time was delayed after several sympathetic stimulations from 134 sec. (5 min. after papaverine injection) to at least 362 sec. (45 minutes after papaverine injection). Stimulation of the inferior hypogastric plexus had no effect on the intracavernous pressure. The neurostimulation range (3-4V; 20 Hz) was most effective in reducing the papaverine action on penile smooth muscles. The effect of sympathetic trunk stimulation seems to antagonize the relaxing action of papaverine on the cavernous smooth muscles and the cavernous arterioles. Our results imply that high sympathetic tone in some patients with psychogenic impotence may explain their poor response to intracavernous injection of papaverine.

Animals↗

Single potential analysis of cavernous electrical activity in impotent patients: a possible diagnostic method for autonomic cavernous dysfunction and cavernous smooth muscle degeneration.

Cavernous electrical activity was recorded in 214 patients with erectile dysfunction and in 39 normal patients. In 34 of the 39 normal patients potentials of a uniform shape were recorded during flaccidity. At cutoff frequencies of 0.5 to 500 Hz. the duration was 8 to 18 seconds (mean 12.8 +/- 2.8, seconds, standard deviation), the amplitude was 250 to 750 microv. (mean 444 +/- 109 microv.) and the polyphasity was 8 to 22 (mean 13.8 +/- 3.3). With increasing tumescence and rigidity during audiovisual sexual stimulation, high frequency potentials of low amplitude and short duration were found in the normal patients. In impotent patients with an upper motor neuron or peripheral lesion specific types of potentials were observed. In 11 of 14 impotent patients with insulin-dependent diabetes for more than 20 years and with clinical findings of cavernous myopathy the potentials showed low amplitude, irregular shape and slow depolarizations. Abnormal findings of cavernous electrical activity were recorded in 51.6% of the consecutive impotent patients. Our clinical study suggests that single potential analysis of cavernous electrical activity may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.

Adult↗

Penile detumescence: characterization of three phases.

In 22 dogs in which erection was induced by cavernous nerve stimulation, we analyzed the intracavernous pressure changes during detumescence without and with acute clamping of the aorta or electrostimulation of the lumbar sympathetic chains. Additionally, the degree of venous outflow obstruction was assessed by saline perfusion of the cavernous body during aortic occlusion. Detumescence had three distinct phases: an initial phase exhibiting a small pressure increase; a second phase showing a slow pressure decrease; and a third phase in which a fast decrease occurred. The first phase was abolished by aortic clamping, whereas the other phases were not significantly affected. Sympathetic stimulation abolished or prevented the second phase. Perfusion of the cavernous body during the second phase resulted in a pressure rise to off-scale values; however, when initiated during the terminal phase or in the nonstimulated penis, the pressure increase was slight. Our study indicates that the arterial flow rate influences the duration of the first phase of detumescence and that venous drainage is completely restored in the third phase. Furthermore, sympathetic stimulation causes an almost immediate full restoration of venous drainage, as cavernous perfusion initiated with an intracavernous pressure about twice as high as without sympathetic stimulation failed to increase pressure to off-scale values.

Animals↗

Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients.

A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5 ng. (2 patients), 50 ng. (2 patients), 500 ng. (4 patients), 5 micrograms (4 patients) and 25 micrograms (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin-gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine. Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin-gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500 ng. to 25 micrograms. Systemic side effects were first observed at a dose of 25 micrograms in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin-gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene-related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence.

Adult↗

Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit.

Using a rabbit model, the involvement of the L-arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4-8 V, 20-30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of: (1) the slope of the initial, ascending part of the pressure increase; (2) delta P, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of delta P. Intrapenile administration of the L-arginine/nitric oxide synthesis inhibitor NG-nitro-L-arginine had no effect on systemic arterial blood pressure. However, NG-nitro-L-arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and delta P decreased significantly. NG-nitro-D-arginine (2.19), on the other hand, had no inhibitory effect. L-arginine (21.07 mg), given either directly or after NG-nitro-L-arginine had no consistent effect on the functional response to cavernous nerve stimulation. The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively, and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG-nitro-L-arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.

Amino Acid Oxidoreductases↗

[Physiopathology of erectile dysfunction due to cavernous venous insufficiency].

Venous insufficiency can cause impotence even in the presence of a normal arterial blood supply. This venous leak may be due to disorders of cavernous tissue (smooth muscle degeneration), disorders of the albuginea (poor compression of the perforating veins), neurotransmitter disturbances or autonomic nervous system disorders. All of these causes result in a pathological venous leak with a raised maintenance flow and abnormal cavernography.

Erectile Dysfunction↗

Diagnosis of venous incompetence in erectile dysfunction. Comparative study of cavernosography and Doppler ultrasound.

In 26 of 214 patients with erectile dysfunction and proved venous incompetence by cavernosography, an additional bidirectional Doppler ultrasound was performed also to demonstrate venous outflow disturbances. All except one leakage in the superficial and deep dorsal veins could be demonstrated as well as 4 of 6 cavernosum-glandular shunts. Bidirectional Doppler ultrasound visualized a continuous retrograde blood flow from the sulcus coronarius to the root of the penis in superficial and deep dorsal penile veins as well as in ectopic penile veins, an orthograde blood flow in the sulcus coronarius in cavernosum-glandular shunt.

Erectile Dysfunction↗

Erectile response to intracavernous injection of vasoactive drugs after penile prosthesis removal.

Two patients with a history of penile prosthesis removal presented for non-prosthetic treatment of their erectile dysfunction. The first patient had a penile implant for two years before it was removed and showed extensive cavernosal fibrosis. He did not respond to intracavernosal injection of vasoactive drugs. The second patient had the prosthesis for four weeks. He showed no evidence of cavernosal fibrosis and responded well to the intracavernous injection. He has been in an intracavernous autoinjection program for more than one year without complications.

Aged↗

The effect of venous incompetence and arterial insufficiency on erectile function: an animal model.

We designed an animal model to elucidate the effect of venous leakage and arterial insufficiency on erectile function. In 10 dogs, electrodes were implanted around the cavernous nerves for electroerection and blood flow in the internal pudendal artery was recorded. Venous leakage was mimicked by inserting needles of varying gauges (30 to 16G) into the corpus cavernosum and the erectile response to neurostimulation was recorded before and after the creation of the leak. The relationship between the size and the amount of the venous leakage, the changes in the intracavernous pressure (peak and drop), and the changes in the peak and maintenance arterial blood flow were documented. Arterial blood flow was then reduced by 25 and 50 per cent by means of a screw clamp on the terminal aorta. The erectile response to neurostimulation was again determined, with the same electrical parameters, first with reduced blood flow alone, then in combination with leakage of varying size. Our results showed that minor cavernous vein leakage in the presence of normal arterial flow and a healthy sinusoidal system had a minimal effect on erectile function owing to a compensatory increase in penile blood flow. However, when reduction of arterial blood flow was superimposed on venous leakage, even of a minor degree, the erectile response to neurostimulation was markedly impaired.

Animals↗

Synchronized electrical stimulation of the sympathetic and parasympathetic innervation of the bladder: facilitation of the initiation of micturition in the dog.

To improve the quality of bladder contractions induced by parasympathetic stimulation and to facilitate the initiation of voiding, we investigated the effect of sympathetic stimulation on the parasympathetic innervation of the bladder in 12 dogs. For the sympathetic system, the lumbar sympathetic trunks were electrically stimulated; for the parasympathetic system, either the pelvic nerve or the ventral root of S2 was stimulated. With voltages at or just above the threshold for achieving a measurable effect on bladder pressure, stimulation of the sympathetic system or the pelvic nerve alone did not lead to voiding, and sacral root stimulation alone elicited voiding in only 7.4 per cent of stimulations. However, when the same stimulus parameters were used for synchronous stimulation, the voiding process was facilitated when sympathetic stimulation was begun five to 10 seconds before parasympathetic stimulation. When the pelvic nerve was used, voiding resulted in 77.7 per cent of stimulations and the bladder was emptied by a mean of 68.7 per cent; with S2 ventral root stimulation, voiding resulted in 83.3 per cent of stimulations and the bladder was emptied by 59.7 per cent. The facilitory effect of sympathetic stimulation was not abolished when the sympathetic trunks were cut centrally to the point of stimulation, but was absent when the hypogastric nerves were transected. We feel that sympathetic stimulation modulates the parasympathetic innervation of the bladder.

Animals↗

A possible role for calcitonin-gene-related peptide in the regulation of the smooth muscle tone of the bladder and penis.

We investigated the effect of calcitonin-gene-related peptide (CGRP) on bladder contractions and penile erection in 12 dogs. In a system in which the arteries were tied bilaterally to ensure delivery of high drug levels to the bladder, arterial injections of CGRP significantly reduced the peak intravesical pressure of bladder contractions induced by pelvic nerve stimulation or arterial injection of carbachol. When given intravenously, CGRP had no effect on bladder contractions consequent to neural stimulation. Intravesical instillation of CGRP, however, reduced the bladder contractions significantly. Histologic staining showed CGRP-immunoreactive nerve fibers within the smooth muscle layers of the bladder wall. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Muscarinic blockade had no effect on the canine intracavernous pressure response to intracavernous injection of CGRP. Histologic staining for CGRP-immunoreactivity showed nerve-fiber-like staining within the cavernous arterial wall, the nerves running near the cavernous arteries, and the cavernous smooth muscles. Our results suggest a possible role for CGRP in the regulation of the smooth muscle tone of the bladder and penis.

Animals↗

Norepinephrine involvement in penile detumescence.

Adrenergic neurotransmission was studied in dogs. Blood samples for catecholamine assay were collected from the flaccid penis, the erect penis after cavernous nerve stimulation and during detumescence induced by sympathetic trunk stimulation. Epinephrine concentration was not significantly different in these three stages. However, norepinephrine concentration increased significantly (p less than 0.005) during induced detumescence from 505 +/- 311 [pg./ml.] to 747 +/- 489 [pg./ml.]. Intracavernous application of norepinephrine abolished cavernous nerve induced erection in a dose dependent manner. Sympathetic trunk stimulation reduced or abolished erection induced by acetylcholine or by vasoactive intestinal polypeptide. We conclude that norepinephrine is an important neurotransmitter in the control of penile detumescence.

Acetylcholine↗

Intracavernous drug delivery system: an alternative to intracavernous injection in the treatment of impotence?

In 6 monkeys, the feasibility of chronic intracavernous drug application via a permanent intracavernous catheter was examined. In 4 monkeys, a combination of papaverine (15 mg/ml) and phentolamine (0.5 mg/ml) was injected via the drug delivery system; in 2 monkeys each, 30 or 100 injections were done. As a control, saline was injected in 2 monkeys. The dose of the papaverine-phentolamine mixture to induce full erection had to be increased by a mean of 240%, comparing the 1st to the 30th injection. The dose then remained stable. After 100 injections, penile histology showed a thin fibrotic layer around the implantation site of the catheter. Beside slight smooth muscle hypertrophy in the papaverine-phentolamine group, there were no abnormal findings in the proximal and medical part of the cavernous bodies. The distal part of the cavernous bodies showed extensive fibrosis due to mechanical irritation by the tip of the intracavernous catheter. Given appropriate selection and indication, implantation of an intracavernous drug delivery system may be an alternative to chronic intracavernous injection in the treatment of impotence.

Animals↗

Quantitative and qualitative analysis of dynamic cavernosographies in erectile dysfunction due to venous leakage.

Of 521 patients with erectile dysfunction in whom a multidisciplinary approach was used, 145 (27.8%) showed venous leakage as (concomitant) etiology of the impotence in dynamic cavernosography. The rate of the maintenance flow corresponded well with the response to a standardized intracavernosal injection of vasoactive drugs (p less than 0.05) in patients with venous leakage. The maintenance flow increased with the age in secondary impotent men. It was not statistically different in patients with or without concomitant arterial insufficiency (p = 0.19). Fifty-one of 145 patients (32.2%) presented a pathologic cavernosal drainage via a single venous system; 94/145 (64.8%) showed a combined venous leakage. The type of leakage corresponded neither to the maintenance flow nor to the response to intracavernosal injections. Our findings show that standardized intracavernosal testing and Doppler have a high predictive value for the status of the venous occlusive system. Exact evaluation of the type of leakage can be made by bidimensional cavernosography only.

Adult↗

Local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline in primates.

To compare the local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline on erectile tissue, eight pigtail monkeys underwent 75 injections over a nine-month period. Monkeys were divided into three groups; each group received papaverine (10 mg.), prostaglandin E1 (20 micrograms.), or saline (one ml.). The erectile response was closely observed for two hours after each injection to monitor the onset, degree, and duration of erection. Liver function tests were performed every three months to detect early systemic metabolic changes. After sacrifice, the simian penises were perfused in situ and examined histologically with both light and electron microscopy. Papaverine resulted in an initially strong erectile response, but this was maintained throughout the length of the study in only two monkeys. In contrast, prostaglandin E1 resulted in tumescence that was maintained in all monkeys over the nine-month period. In addition, the papaverine group had elevated liver enzymes and significant histologic changes with loss of normal architecture on both light and electron microscopy. The other two groups showed only minimal histologic changes or none.

Alprostadil↗