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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

At least 73 records · Page 4Linked to original sources

Possible role of human growth hormone in penile erection.

PURPOSE: Treatment with recombinant human growth hormone in adult patients with growth hormone deficiency increases nitric oxide and cyclic guanosine monophosphate (cGMP). We examined the functional in vitro effects of recombinant human growth hormone on tissue tension and cyclic nucleotide levels of human corpus cavernosum and detected changes in growth hormone in the cavernous and peripheral blood during different phases of penile erection. MATERIALS AND METHODS: Relaxant responses of human corpus cavernosum were investigated using the organ bath technique. Tissue levels of cGMP were determined by a specific radioimmunoassay after dose dependent exposition of isolated human corpus cavernosum strips to recombinant human growth hormone. In 35 healthy potent volunteers blood samples were obtained simultaneously from the corpus cavernosum and cubital vein during different functional conditions of the penis, including flaccidity, tumescence, rigidity and detumescence. Penile erection was induced by audiovisual and tactile stimulation. Serum growth hormone was determined by an immunoradiometric assay. RESULTS: Recombinant human growth hormone elicited dose dependent relaxation of human corpus cavernosum strips in vitro. The relaxing potency of recombinant human growth hormone was paralleled by its ability to elevate intracellular levels of cGMP. In vivo the peripheral growth hormone serum profile of the respective penile conditions did not significantly differ from those of cavernous serum. The main increase in growth hormone to greater than 90% was determined during developing penile tumescence, followed by a transient decrease afterward. CONCLUSIONS: These results suggest that penile erection may probably be induced by growth hormone through its cGMP stimulating activity on human corpus cavernosum smooth muscle.

Adult↗

Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum.

The hydrolysis of the second messenger cyclic AMP (cAMP) by phosphodiesterase 3 (PDE3) is known to play an important regulatory role in the context of relaxation of cavernous smooth muscle of the penis. Thus, we investigated the PDE3A isoform from penile cavernous tissues of male patients with and without symptoms of erectile dysfunction at the molecular biological level. As revealed by reverse transcriptase polymerase chain reaction, of all tissues of the urogenital tract analyzed the expression of the PDE3A gene was highest in the corpus cavernosum. However, significant differences in the levels of gene expression were not found between the two subgroups of patients. Also, the determined nucleotide sequences of the cloned penile PDE3A cDNAs of all patients were absolutely identical. Surprisingly, some deviations could be detected in the cDNA sequences of PDE3A from human myocard and platelets. The data obtained indicate that neither the expression levels nor the sequence deviations of PDE3A are the main reasons for erectile dysfunction in men.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Therapy for kidney cell carcinoma with cava thrombus. Importance of extracorporeal circulation and prognostic value of cranial tumor extension].

In approximately 4-10 % of patients presenting with renal cell cancer the transluminal propagation of a tumor thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension it was clearly demonstrated that the use of cardiopulmonary bypass, deep hypothermia and circulatory arrest preferably during the removal of intracaval thrombosis extending into the right atrium does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Adult↗

Petroleum jelly is an ideal contact medium for pain reduction and successful treatment with extracorporeal shock wave lithotripsy.

PURPOSE: Various minimally invasive approaches to reduce pain during extracorporeal shock wave lithotripsy (ESWL) have been described. We compared petroleum jelly (Vaselinet) and ultrasound gel in vitro as a contact medium based on the stone fragmentation rate. The analgesic effect of cutaneous petroleum jelly was tested against eutectic mixture of local anesthesia. We also evaluated the outcome of ESWL in a large group of patients treated with petroleum jelly. MATERIALS AND METHODS: In vitro 3 artificial stones were completely fragmented with a MFL 5000* lithotriptor using petroleum jelly or ultrasound gel as a contact medium. A total of 110 patients (group 1) received petroleum jelly before treatment with the same lithotriptor. After retrospective analysis of group 1 we matched 32 patients (group 2) receiving cutaneous eutectic mixture of local anesthesia. Because of the favorable results with petroleum jelly, we used it in another 148 patients, for a total of 258 patients (group V). Treatment dependent pain was scored using a questionnaire as 1--no, 2--minor, 3--tolerable and 4--intolerable. ESWL without additional analgesics had a pain score of 1 to 3. RESULTS: In vitro petroleum jelly had a superior fragmentation rate compared to ultrasound gel. Our long-term experience with the lithotriptor indicated that only 30% of patients required no additional analgesics with cutaneous ultrasound gel. In contrast, no additional analgesics were needed in only 38% of group 2 compared to 81.8% of group V. The stone fragmentation rate did not differ statistically between groups. CONCLUSIONS: Cutaneous petroleum jelly offers a noninvasive, highly effective, inexpensive treatment modality with no side effects and significant reduction in pain. This ointment is our contact medium of choice.

Anesthetics, Local↗

Physiology and pathophysiology of erection: consequences for present medical therapy of erectile dysfunction.

Smooth muscle relaxation of the corpus cavernosum is the key mechanism of erection. It depends on a cascade of consecutive regulatory systems starting in the central nervous system, and proceeding via peripheral neurotransmission to intracellular signal transmission within the cavernous smooth muscle cells. Knowledge of these interacting mechanisms of erection is fundamental for understanding of the mode of action of new and possibly selective pharmacological agents that are presently available or under evaluation for treatment of erectile dysfunction.

Biomechanical Phenomena↗

[Prognostic relevance of vena cava thrombosis in renal cell carcinoma].

The independent prognostic value of neoplastic extension of renal cell cancer (RCC) into the vena cava inferior has been the subject of several investigations reported to date. However, the use of vena cava thrombosis as an independent prognosticator of a patient's long-term survival is still debated. We have therefore correlated the clinical course of 53 patients with RCC and vena cava thrombosis with a control group consisting of 47 patients with renal cell tumors without vena cava thrombosis (follow-up: 1-154 months). The median long-term survival of patients with and without vena cava thrombosis was 32 and 35 months, respectively. Neither the propagation of the tumor into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158)--even in case of propagation into the right atrium--could be identified as parameters of any prognostic value during univariate or multivariate statistical analysis.

Adult↗

[Pharmacological therapy of erectile dysfunction].

Pharmacotherapy of erectile dysfunction comprises oral and local application of drugs. Today, Yohimbin is the only drug listed for this indication. Yohimbin acts via central alpha-receptor blockade and showed a significant effect in a recent double blind study compared to placebo. The centrally acting substances Apomorphin and Trazodone were also tested for their potential use with Apomorphin showing promising results. The orally active phosphodiesterase-V inhibitor Sildenafil acts predominantly on the peripheral side; broad clinical studies demonstrated a significant effect of the drugs compared to placebo. For local use, intraurethral (MUSE) and intracavernous applications are available with PGE1 being the drug the most widely used for the moment. Since many different drugs with various modes of action and different modes of application are being developed at the moment, future pharmacological treatments will allow a more refined approach towards an individually adapted regimen.

Adrenergic alpha-Antagonists↗

The effect of the specific phosphodiesterase-IV-inhibitor rolipram on the ureteral peristalsis of the rabbit in vitro and in vivo.

PURPOSE: Cyclic nucleotide phosphodiesterases (PDE's) are intracellular key enzymes in the regulation of the tone in smooth muscle cells. There are 5 different isoenzyme families that show a specific organ and species distribution pattern. The aim of our study was to examine possible selective ureteral relaxation by the specific PDE-IV-inhibitor rolipram in the rabbit. MATERIALS AND METHODS: For in vitro studies ureters were taken from 12 patients who underwent radical nephrectomy and from 4 rabbits which were sacrificed. For the in vivo study 23 rabbits received intravenous administration of papaverine (300 microg./kg. b.w., n = 2), scopolamine (667 microg./kg. b.w., n = 2), theophylline (5 mg./kg. b.w., n = 2) and rolipram (5 and 20 microg./kg. b.w., n = 9 and n = 8). Ureteral dynamic parameters (frequency, amplitude, tonus) and systemic blood pressure were continuously monitored 40 minutes before and at least 60 minutes after injection of the drugs. RESULTS: Scopolamine had no effect on ureteral peristalsis, but significant effects on systemic blood pressure were observed. Papaverine and theophylline showed short-lasting ureteral relaxations, but were accompanied by severe circulatory side effects. Rolipram showed pronounced ureteral relaxation with minimal circulatory effects. CONCLUSION: Our results show that intravenous administration of the specific PDE-IV-inhibitor rolipram relaxes the rabbit ureter without significant circulatory side effects. Because human and rabbit ureter show similar relaxation results in vitro, this pharmacological approach seems promising for the treatment of ureteral colic and the facilitation of urinary stone passage in humans.

Animals↗

Uncircumcision: a historical review of preputial restoration.

Throughout history, demands for restoration of the prepuce after circumcision were most commonly related to the political or religious persecution of the Jewish people. The first evidence for such a procedure is mentioned in the Bible: Under the reign of Antiochus IV (168 BC) Hellenistic ideals, such as public nakedness at athletic games or in public baths, emerged in Judea and forced Jews to stretch their shortened foreskins with a special weight, the Pondus Judaeus, to cover the glans (I. Maccabees 1). Similar efforts are reported in the Talmud during the time of Hadrian (132 AD). Celsius (25 BC-50 AD) was the first to give a detailed description of two surgical techniques for uncircumcision in his De medicina libri octo. Subsequent works, for example by Galen (131-200 AD) and Paulus Aeginata in the seventh century, only contained a repetition of these methods without presenting any new aspects. Ambroise Paré gave a new impetus in the sixteenth century, suggesting the insertion of a catheter into the distal urethra to guarantee free passage of urine during postoperative healing. In this past century, Johann Friedrich Dieffenbach was the first to dedicate a whole chapter to the problem of "posthioplastice" in a modern textbook of plastic surgery. Almost no written documents exist of uncircumcision during the Nazi era; nevertheless, surgical treatment seemed to be widespread as every circumcised man was in danger of being denounced as a Jew. Personal reports of patients and doctors performing surgical restoration of the prepuce are presented. Nowadays, reports on surgical foreskin restoration are still rare and alternative methods of nonsurgical skin-expansion have become more common. Several organizations were founded in America against routine infant circumcision and give advice to foreskin restoration seekers.

Circumcision, Male↗

Surgical strategy in late-stage renal cell cancer with intracaval extension.

During the past two years several reports have substantially contributed to the surgical stratification of patients with late-stage renal cell cancer and simultaneously occurring intracaval neoplastic extension, and our knowledge about the clinical prognosis of the patients after nephrectomy with complete removal of the tumour thrombosis has been extended. Recognizing the importance of a tolerable perioperative and postoperative morbidity and mortality, it is now well documented in the literature that a multidisciplinary approach involving the combined use of deep hypothermia, cardiac arrest and cardiopulmonary bypass has dramatically improved the feasibility of surgical treatment of the venous extension above the hepatic veins. Furthermore, the diagnostic approach for patients with intracaval thrombosis, aiming at the reliable delineation of the cranial margin of venous extension, has been rationalized without compromising important diagnostic information required for the surgical stratification. This review assesses the current opinion of the surgical stratification of patients with renal cell cancer and intracaval neoplastic extension, the most reliable and least invasive diagnostic approach for the preoperative staging and, finally, the independent prognostic value of neoplastic venous extension for the clinical course of the disease.

Journal Article↗

Phosphodiesterase inhibitors in the treatment of erectile dysfunction.

Based on knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation and the development of new and selective pharmacological agents, selective phosphodiesterase (PDE) inhibitors were recently introduced for the treatment of erectile dysfunction. By molecular biological methods, PDE isoenzymes III, IV and V were characterized in the human cavernous smooth muscles. In functional organ bath studies using precontracted human cavernous tissue strips, PDE III and V inhibitors showed the most pronounced relaxant responses. In clinical studies, the use of the orally active PDE V inhibitor sildenafil induced a pronounced and significant erectogenic effect in patients with both predominantly psychogenic and organogenic etiology of erectile dysfunction. The first promising clinical data on the use of an orally active PDE inhibitor for the treatment of erectile dysfunction are well supported by consistent basic science findings. Further research will possibly allow to identify diagnostic tools for erectile dysfunction and for even more selective drugs in its therapy.

Journal Article↗

Oral phentolamine as treatment for erectile dysfunction.

PURPOSE: For most patients with erectile dysfunction oral agents are a preferred treatment option. Oral or buccal phentolamine has been shown to produce full erections in impotent subsets of study populations. We evaluate the efficacy of oral phentolamine. MATERIALS AND METHODS: After a comprehensive evaluation 44 patients with recent onset (less than 3 years) of erectile dysfunction and a high likelihood of organogenic etiology underwent a prospective, double-blind and placebo controlled trial with oral phentolamine after placebo. RESULTS: After placebo 4 of the 44 patients who reported full erections were excluded from study. Of the 40 patients in the double-blind phase full erections were achieved by 2 of 10 with placebo, and 3 of 10 with 20 mg., 5 of 10 with 40 mg. and 4 of 10 with 60 mg. phentolamine. There were no serious complications observed during the study, and only a single minor side effect occurred in 1 patient after 60 mg. phentolamine. CONCLUSIONS: Our results indicate that oral phentolamine may be of benefit for the treatment of erectile dysfunction. Further studies are required to corroborate our findings.

Administration, Oral↗

The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo.

PURPOSE: Phosphodiesterases (PDE) are key enzymes in the regulation of the smooth muscle tone. Experimental studies showed PDE III and V-isoenzymes to play an important role in the smooth muscle tone regulation of corpus cavernosum. Recently, a specific PDE III-inhibitor (milrinone) and a PDE V-inhibitor (sildenafil) were introduced in clinical studies. An experimental study was done to examine a potential role of PDE-inhibitors in the treatment of erectile dysfunction. MATERIALS AND METHODS: In the organ bath, strips from human and rabbit corpus cavernosum were precontracted and increasing doses of PDE inhibitors were added. In patients with erectile dysfunction as well as in rabbits, intracavernous injections of milrinone were done. RESULTS: PDE-inhibitors dose-dependently relaxed human and rabbit corpus cavernosum strips. In the precontracted human cavernous tissue, milrinone and sildenafil were equally potent and efficacious in vitro. In the rabbit, milrinone induced slight tumescence but dramatic circulatory side effects. In patients, penile tumescences as well as full erections were observed. CONCLUSIONS: Milrinone strongly relaxes human cavernous smooth muscle cells but it exhibits low relaxant effects in the rabbit cavernous tissue. In human tissue, sildenafil was equieffective with milrinone in vitro. In vivo, milrinone induced a good erectile response in humans but a poor erectile effect in rabbits. Our results support a possible potential for selective PDE-III and -V inhibitors in the treatment of impotence and give further evidence that the rabbit is an animal model of limited value to study the effects of drugs on cavernous smooth muscle tone regulation in vivo.

Animals↗