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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

At least 19 recordsLinked to original sources

Effects of cytokines on growth in vitro of primary human renal cell carcinoma.

In clinical trials different haematopoietic active cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) have been proven to alleviate myelosuppressive side effects of intensive chemotherapy in different non-urological malignancies. On the other hand, these cytokines can directly stimulate the proliferation of cells originating from some non-urological tumours. To clarify the impact of these cytokines on the proliferative behaviour of human renal cell carcinoma (RCC), 29 previously untreated RCC tumours were prepared for culturing in vitro using the cell cluster technique. The success rate for growth in vitro was 82.8% (24/29). The malignant renal cells were treated with different cytokines (GM-CSF, G-CSF and interleukin-3) in different dosages. Cell number and proliferation rates detected by immunostaining were used for treatment evaluation. A dosage-dependent stimulation of cell growth could not be observed compared to untreated cells. From the data presented in this study, proliferative stimulation of RCC by administering colony-stimulating factors in clinical trials cannot be assumed.

Carcinoma, Renal Cell

The influence of anterior root stimulation (S2) in deafferented spinal cord injury men on cavernous electrical activity.

Registration of cavernous electrical activity (single potential analysis of cavernous electrical activity) was recently suggested for the diagnosis of autonomic cavernous dysfunction. For validation of this method the effect of sacral neurostimulation on cavernous electrical activity was examined. In 3 male patients with a complete spinal cord lesion (T3, T4 and T12, respectively), deafferentation was done at the S2 to S5 levels. Around the anterior roots of S2 to S5 electrodes for neurostimulation were placed. Cavernous electrical activity was recorded with an intracavernous needle electrode and with surface electrodes in the flaccid as well as in the erect states induced by neurostimulation (at 7, 8, 12, 18, 20, 30 and 45 Hz., 30 v. and 0.4 msec). In all patients similar potentials compared to the normal values, as well as additional pathological potentials were recorded during flaccidity. During neurostimulation all patients achieved full erection with no or markedly decreased cavernous electrical activity to frequencies of 12, 18, 20 and 30 Hz., while to 7, 8 and, more pronounced, 45 Hz. only partial erection with ongoing cavernous electrical activity was found. Our study strongly suggests that cavernous electrical activity and, subsequently, the cavernous smooth muscle tone are dependent on autonomic input. This finding supports the hypothesis that single potential analysis of cavernous electrical activity may be valid in the diagnosis of cavernous autonomic dysfunction. Furthermore, our results suggest a possible role for single potential analysis of cavernous electrical activity in the fine tuning of erection inducing neurostimulators.

Adult

Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection.

We investigated the effects of intracavernous injection of a combination of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) on the erectile response in eleven adult male dogs. The minimum dose of ACh which increased the intracavernous pressure in eight dogs varied from 0.2 to 40 micrograms, and the minimum dose of VIP varied from 0.2 to 5 micrograms. When the minimum doses of ACh and VIP were injected simultaneously, a strong increase of intracavernous pressure (the mean increase was 102 cm. H2O from the baseline level) and a sustained erection (mean 5 min.) were observed in all eight dogs. The effect of simultaneous injection of both drugs was not additive but synergistic. Pretreatment with VIP-antibody and atropine intracavernously suppressed the erectile response induced by cavernous nerve stimulation. VIP may increase the affinity of muscarinic receptors for ACh in canine corpus cavernosum because pretreatment with atropine alone before the simultaneous injection of ACh and VIP completely abolished the effect of the combination. We conclude that ACh and VIP may play a cooperative role in canine penile erection.

Acetylcholine

A new therapeutic concept for long-lasting iatrogenic priapism: a case report.

In a therapeutic attempt on an 18-year-old patient with iatrogenic priapism lasting for more than 2 weeks after internal urethrotomy, intracavernous lysis was commenced with 80,000 IU streptokinase per hour. Following a dosage of 300,000 IU streptokinase the lysis was stopped because of severe bleeding from the urethrotomy scar. At 4 weeks after the patient was discharged from the hospital he reported normal erections and intercourse, while single potential analysis of cavernous electrical activity and ultrasound returned to normal. Provided there are no contraindications, intracavernous lysis seems to be an effective treatment for long-lasting priapism induced by intracavernous thrombosis.

Adolescent

Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction.

Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitric oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. SIN-1 were injected intracavernously in patients with erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. SIN-1, including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond with a full erection to other pharmacological agents. Intracavernous injection of SIN-1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a full, 21 an almost full and 13 a moderate erection to 1 mg. SIN-1. There were no systemic or local side effects. In the patients with prolonged erections to papaverine plus phentolamine the mean duration of a full erectile response to SIN-1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by SIN-1 was superior in 10, comparable in 47 and inferior in 6 patients. Our data suggest a possible role for SIN-1 in the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs.

Blood Flow Velocity

Transcutaneous registration of cavernous smooth muscle electrical activity: noninvasive diagnosis of neurogenic autonomic impotence.

Registration of cavernous electrical activity was shown to be a possible method for the evaluation of cavernous autonomic innervation. Recent studies in patients with normal erectile function showed that cavernous electrical activity is synchronous throughout the entire cavernous bodies. Therefore, we examined the feasibility of transcutaneous registration of cavernous electrical activity in 8 normal and 62 impotent patients. In the sitting patient cavernous electrical activity was recorded with a 2-channel electrophysiological unit. Recording was done with a coaxial needle electrode in the proximal left cavernous body and with surface electrodes bilaterally on the penile shaft. In 7 of 8 normal patients swelling of the penile shaft after circumcision resulted in a dramatically decreased amplitude of the potentials. In 41 of 62 impotent patients recordings were similar. In 10 of 62 patients no recording or markedly decreased amplitudes were noted with the surface electrodes and in these patients a small penis or penile retraction with consecutive electrode displacement was found. Careful repositioning of the surface electrodes with the patient in the supine position resulted in similar recordings in 9 (inconsistently in 4). In 11 of the 62 patients more information was obtained with the surface than with the needle electrode. Our results show that recording of cavernous electrical activity can be done in a completely noninvasive manner using surface electrodes with similar or even better information obtained than with needle electrodes.

Action Potentials

[Vasectomy: minor intervention--grave sequelae].

Claims for compensation following dissatisfaction with the results of medical treatment have increased in frequency over the last few years. Medical records, such as declarations of consent and operation reports, often constitute important evidence in legal proceedings, particularly in the field of surgery. Before a vasectomy is performed for the purpose of contraception, detailed information must be given on how safe this is as a method of birth control and the patient must be made aware of the importance of sperm count controls after the operation. The surgeon is held responsible if it can be shown that a failed sterilization is due to ligation of only one vas deferens or to failure to notice an accessory one. Claims for compensation can include support for children up to the age of 18 years and financial compensation to the mother in respect of the labour pains.

Humans

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