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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

At least 109 records · Page 6Linked to original sources

Application of factor analysis for the determination of specific frequency bands in corpus cavernosum EMG power density spectra.

Corpus cavernosum electromyogram (CC-EMG) recording provides diagnostic information on cavernous autonomic innervation and the intact state of cavernous smooth muscle cells. Evaluation of these signals is time consuming and complex. Therefore, we attempted to facilitate their interpretation and to increase their objectivity by using computer-based digital signal processing. Spectral parameters were used as a starting point for this analysis, which were calculated from the Fourier-transformed time domain CC-EMGs. Factor analysis was applied to determine specific frequency bands in the CC-EMG power density. Two hundred power spectra, taken from normal subjects (n = 66) and from patients suffering from erectile dysfunction (n = 134), constituted the basic data. As a result of applying factor analysis, four specific frequency bands were depicted: 0.0-0.3, 0.3-3.5, 3.5-6.0 and 6.0-10.0 Hz. The results of this study form the basis for further mathematical evaluation and calculation of the CC-EMG for clinical and diagnostic purposes.

Adult↗

A possible role for nitric oxide in the regulation of human ureteral smooth muscle tone in vitro.

There is ample evidence that nitric oxide (NO) is an important neurotransmitter in many tissues of the urogenital tract. The aim of the present study was to examine the possible role of NO in ureteral relaxation. Human ureteral rings were mounted in organ bath chambers and precontracted in KCl. Increasing doses of the NO donor linsidomine (SIN-1) were added with and without prior blockade of the NO/cGMP pathway by methylene blue and protein kinase (PK) inhibitors Rp-8-pCPT-cGMPS and RP-8-CPT-cAMPS. Electrical filed stimulation (EFS) was done before and after incubation with L-NOARG (NG-nitro-L-arginine) and TTX (tetratodoxin). For detection of neuronal NO synthase (NOS), ureters were stained immunohistochemically. Ureteral strips were dose dependently relaxed by SIN-1; preincubation with methylene blue and protein kinase G inhibitor significantly reduced the SIN-1-induced relaxations. No effects of L-NOARG and TTX on EFS-induced tone alterations were found. NOS-positive neuronal axons and nerve-ending-like structures were found in the muscular layers. Our in vitro findings suggest that ureteral relaxation may involve the NO pathway.

Cyclic GMP↗

Electrical and chemical control of smooth muscle activity of rabbit corpus cavernosum in vitro.

OBJECTIVES: This study sought to further elucidate the regulation of cavernous smooth muscle tone and to characterize mechanisms of cavernous activation and relaxation. METHODS: In isolated strips of rabbit corpus cavernosum, extracellular electrical and mechanical activity were recorded simultaneously before and after pharmacologic stimulation. RESULTS: Spontaneous mechanical activity was characterized by fast phasic contractions (frequency 6 to 30 min-1) associated with fluctuations of the extracellular electrical signals. Phasic activity was increased by blockade of potassium channels or by moderate activation of L-type calcium channels. Faster spikelike fluctuations occurred in the electrical activity, indicating the existence of spike discharges. All mechanical and electrical fluctuations were completely abolished by blockade of L-type calcium channels with nifedipine. CONCLUSIONS: Our results indicate that cavernous smooth muscle tone is regulated by both phasic and tonic activation mechanisms caused by the opening of L-type calcium channels and calcium influx through chemically controlled calcium influx/release.

Animals↗

[Functional electromyostimulation of the penile corpus cavernosum (FEMCC)]. Initial results of a new therapeutic option of erectile dysfunction].

Transcutaneous application of low-frequency electric current in the treatment of partially or temporarily denervated striated muscles is widely used to prevent or treat muscular atrophy. Due to the high regenerative capacity of smooth muscle cells, this approach should be beneficial in the treatment of diseases with smooth muscle degeneration due to partial denervation. Our study was done to evaluate the possible beneficial effect of transcutaneous application of low-frequency electric current to the corpus cavernosum penis in the treatment of erectile dysfunction. After a comprehensive work-up, 22 patients with chronic erectile dysfunction (21/22 vasoactive nonresponders) received daily (3-5 x 20 min) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles (FEMCC; zero line symmetric impulses of trapezoid shape, two-channel device with alternating stimulations, f = 10-20 Hz for channel I and 20-35 Hz for channel II; t(i) = 100-2000 microseconds, approx. 12 mA, rise time 0.5 s, stimulation time 5 s per channel, interval between stimulations 0.5 s). Five of 22 patients (23%) regained full spontaneous erections and another three (14%) responded to vasoactive drugs after FEMCC. Fourteen were FEMCC failures, including two who subjectively 'improved'. In a similar group of patients evaluated during the same period but receiving no therapy, no spontaneous improvement of the erectile function was observed. Our preliminary results suggest that FEMCC is feasible and results in an improvement of the erectile capacity in a significant proportion (37%) of patients. Further studies will be carried out to corroborate our results, to improve stimulation parameters and to evaluate selection criteria for FEMCC.

Adult↗

Functional electromyostimulation of the corpus cavernosum penis--preliminary results of a novel therapeutic option for erectile dysfunction.

Transcutaneous application of low-frequency electric current in the treatment of partially or temporarily denervated striated muscles is widely used to prevent or treat muscular atrophy. Due to the high regenerative capacity of smooth-muscle cells, this approach should be beneficial in the treatment of diseases with smooth-muscle degeneration due to partial denervation. Our study was done to evaluate the possible beneficial effect of transcutaneously applied low-frequency electric current on the corpus cavernosum penis in the treatment of erectile dysfunction. After a comprehensive workup, 21 patients with chronic erectile dysfunction (20/21 vasoactive nonresponders) received daily (3-5 x 20 min) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles [FEMCC; zero-line symmetric impulses of trapezoid shape, 2-channel device with alternating stimulations; frequency (f), 10-20 Hz for channel I and 20-35 Hz for channel II; impulse duration (ti), 100-150 microseconds; approx. 12 mA; rise time, 0.5 s; stimulation time, 5 s/channel; pause between stimulations, 0.5 s. In all, 4/21 patients (19%) regained full spontaneous erections and another 3/21 (14%) responded to vasoactive drugs after FEMCC. Overall, 14/21 were FEMCC failures, including 2 who subjectively "improved." In a similar group of patients who were evaluated during the same period but received no therapy, no spontaneous improvement in erectile function was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Denovo urothelial carcinoma of the upper and lower urinary tract in kidney--transplant patients with end-stage analgesic nephropathy.

Patients with end-stage analgesic nephropathy bear a higher risk for urothelial cancer than do patients with other renal diseases. In a retrospective study in patients with analgesic nephropathy and kidney transplants we analyzed the prevalence and clinical course of de novo urothelial cancer. Diagnosis of analgesic nephropathy was based on the patients' history and clinical data. Only patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371 kidney transplants were performed on 2,072 patients in the Department of Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was 3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10 (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer occurred on average at 33.6 months posttransplantation. On average, 6 of 10 patients with urothelial cancer died of the disease at 16.9 months after the diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in 9.1% of our patients with analgesic nephropathy and urological screening is insufficient in patients on dialysis, we suggest that prophylactic nephroureterectomy be performed on one side before transplantation and on the contralateral side at 3-6 months after transplantation. An aggressive approach is indicated in patients with urothelial cancer of the bladder.

Analgesics↗

Localized renal-cell carcinoma: detection of abnormal cells in peritumoral tissue. A cytophotometry and immunocytochemistry study.

To spare organ function, partial resection of early diagnosed renal-cell carcinoma (RCC) is applied for well-localized and small-volume RCC with increasing frequency, although recurrence of the tumor in the same kidney is occasionally observed. The aim of the present study was to establish objective prognostic parameters that would allow the selection of tumors suitable for an organsaving procedure. Of the 160 patients undergoing a radical nephrectomy, 67 were included in this study. In 7/45 patients with lymph-node dissection (15.6%), clinical staging revealed a false-negative lymph-node status. By means of conventional histopathology, multifocality could be demonstrated in 2/67 patients (3%); in 1/67 patients (1.5%), the ipsilateral adrenal gland was unexpectantly tumor-involved. Both tumor tissue and normal peritumoral tissue were examined for the presence of premalignant and tumor cells on the basis of DNA ploidy and of the expression of the tumor-associated G250 antigen, which is specifically expressed at the surface of renal cancer cells. In 40/67 (59.1%) peritumoral tissue specimens, cells with an abnormal DNA content could be observed using automated image analysis. In 12/67 cases (18%), cells obtained from peritumoral tissue also showed an aneuploid DNA histogram; 4/67 (6%) had a tumor-correlated DNA ploidy. Additionally, 38/67 (56.9%) of these tissues, histopathologically classified as normal, contained cells expressing the G250 antigen. These observations were independent of the stage or histological grade of the tumor. These data indicate that classic pathological parameters for tumor staging are insufficient for the detection of multifocality, occurring in more than 15% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renal-cell carcinoma with intracaval neoplastic extension: stratification and surgical technique.

Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.

Aged↗

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↗

Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro.

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.

Chromatography, Ion Exchange↗

Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro.

An increase in cyclic nucleotide monophosphate levels is suggested to play a prominent role in mediating smooth-muscle relaxation. Cyclic nucleotide phosphodiesterase (PDE) influences smooth-muscle tone by decreasing the level of cyclic nucleotides. At present, five different families of isoenzymes of PDE exist that show a distinct species- and organ-specific distribution. Our study was done to evaluate the existence of specific PDE isoenzymes and its functional role in human ureteral tissue. Normal ureteral tissue was homogenized and centrifuged and the supernatant fraction was separated using anioin-exchange diethylaminoethyl (DEAE)-Sephacel chromatography. A PDE assay was then performed and the peak fractions were added to different specific PDE activators and inhibitors. In vitro, longitudinal ureteral strips were precontracted and different selective and non-selective PDE inhibitors were added incremently. Three different PDE isoenzymes were characterized: PDE I (calmodulin-sensitive), PDE II (cGMP-stimulated), and PDE IV (cAMP-specific). All PDE inhibitors relaxed the strips dose-dependently, with the 50% effective concentrations (EC50) being 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low-level effect on the systemic circulatory parameters, may open the possibility of using selective PDE IV-inhibitors in the treatment of ureteral colics or for ureteral stone passage.

3',5'-Cyclic-AMP Phosphodiesterases↗

Single potential analysis of cavernous electrical activity in spinal cord injury patients.

Introduced in 1988, cavernous electromyography and its evolution, single potential analysis of cavernous electrical activity (SPACE), seem to be promising diagnostic methods in the evaluation of erectile dysfunction. The aim of our study was to determine the influence of a centrally disturbed autonomic supply on SPACE recordings. SPACE was performed in 35 male patients with complete and 2 with incomplete spinal cord lesions at a cervical or thoracic level. Simultaneous recording was done with concentric needle electrodes in both cavernous bodies with a frequency range of 0.5 to 100 Hz. All patients underwent a full neurological and urological evaluation, including cystometry. The lesion was cervical in 12 patients and thoracic in 22. Three patients underwent sacral deafferentation and bladder pacemaker implantation. One of 12 patients with cervical and 10 of 22 with thoracic lesions reported full rigid reflexogenic erections, while 3 of 12 patients with cervical lesions were not evaluable due to grounding failure. Of these patients 31 were eligible for our study. No patient had an entirely normal SPACE. Four of 9 patients with cervical and 19 of 22 with thoracic lesions had a normal, silent basic electric (less than 5 mu v.) oscillation, while the remainder had a baseline oscillation of up to 100 mu v. Normal potentials were found in 2 of 9 and 10 of 22 patients, respectively. Low frequency, high amplitude potentials were found in 6 of 9 and 21 of 22 patients, respectively, while low frequency, low amplitude potentials occurred in 8 and 8, respectively, and high frequency potentials occurred in 5 and 1, respectively. Our results show that abnormal autonomic input induces abnormal SPACE findings in patients with (presumably) normal cavernous tissue.

Action Potentials↗

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↗

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↗

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↗