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Biomedical subjects

C G Stief

Publications and source records attributed to C G Stief.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Drug therapy of erectile dysfunction--the current status].

In the medicinal therapy of erectile dysfunction (ED), both oral as well as local application are possible. The introduction of the PDE-5 inhibitor Sildenafil, as the first highly potent oral therapy for ED, caused dramatic changes in the diagnostic and therapeutic strategies in this area. The later PDE-5 inhibitors Tadalafil and Vardenafil show, as far as it is currently possible to judge, a similar profile to Sildenafil. The only previously available oral therapeutic, Yohimbin, plays an insignificant role, and the initial hopes for Apomorphin as an ED therapeutic have settled to a realistic level. Local application therapies have also become less important, with the intra-urethral application of PGE(1) being reduced to a few clinical indicated situations. The intra-cavernosal pharmacotherapy with PGE(1) is considered the gold standard when oral therapies do not work or can not be used.

Administration, Oral↗
PubMed2003

Central mechanisms of erectile dysfunction: what a clinician may want to know.

The interplay between peripheral and central mechanisms of erectile function are not fully elucidated although basic science is moving ahead in this area. It is important from a clinical point of view to understand these mechanisms so that we may begin to make further therapeutic advances in the treatment of erectile dysfunction (ED). It is now widely understood that central disinhibition plays a crucial role in the induction of erectile responses and this has led to the development of the central initiator, apomorphine SL (Ixense ) [apo SL]. Apo SL acts in the paraventricular nucleus of the hypothalamus as a dopamine receptor agonist. It works as a proerectile conditioner at this level to increase the responses of the erectile pathway following appropriate sexual stimulation. This unique central mode of action of apo SL has thus proved efficacious in approximately 70% of ED patients although persistence may be required to produce a robust effect for the maximum number of patients.

Erectile Dysfunction↗
PubMed2003

Ureteric reconstruction.

Although the ureter is functionally simply a tube to transport urine, ureteric surgery requires detailed anatomical knowledge and advanced surgical skills, because the ureter has a delicate blood supply. Therefore, the urological surgeon must have distinct strategies available to bridge ureteric defects of various sites and lengths. Furthermore, handling during and after surgery should be individualized to the patient's pre- and intraoperative situation. In this review, the indications for reconstruction of a specific ureteric defect, the required techniques and postoperative recommendations are discussed.

Humans↗
PubMed2003

In vitro construction of urinary bladder wall using porcine primary cells reseeded on acellularized bladder matrix and small intestinal submucosa.

BACKGROUND: Partial or radical cystectomy requires replacement of the urinary reservoir normally achieved by using small or large bowel segments. Our aim was to establish tissue engineering of an bioartificial bladder wall using primary cultures of porcine urothelial (pUC) and bladder smooth muscle cells (pSMC) to be reseeded on different acellular biological matrices. METHODS: Primary porcine cultures of pUC and pSMC were established from open bladder biopsy material 25 mm2 in size. Acellular matrix was generated either from a) porcine bladder wall segments or b) tubular small intestinal submucosa with the still attached decellularized muscularis layer. Reseeding of these matrices with primary cells was done in a two-dimensional static model and in a three-dimensional rotating bioreactor perfused with cell culture medium for a period of 6 weeks. RESULTS: Prior to reseeding the cultured cells were characterized as pUC and pSMC by immunohistochemical staining with either anti-keratin 7 or anti-alpha actin. For both matrices a reseeded double layer cell system of pUC and pSMC could be identified after incubation in the described systems for 6 weeks. CONCLUSIONS: Our results document successful generation of tissue engineered urinary bladder wall, which can be used in further large animal transplantation experiments.

Animals↗
PubMed2002

Is there a common pathophysiology of erectile dysfunction and how does this relate to new pharmacotherapies?

Many basic and clinical studies show erectile dysfunction (ED) to be caused by a wide variety of factors. Although these factors can be divided into psychological and organic origins and these too can further be subdivided, many patients will show complex patterns of causes for ED ('mixed ED'). Many of these factors will have a direct or indirect impact on the efficacy of centrally and peripherally acting drugs, thus necessitating a variety of drugs with different modes of action and different modes of application to ensure appropriate therapy for many patients. However, some factors will render all imaginable forms of pharmacological options totally inefficient, thus necessitating forms of treatment other than pharmacotherapy.

Autonomic Nervous System↗
PubMed2002

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Erectile Dysfunction↗
PubMed2002

Growth hormone, somatomedins and men's health.

According to current basic science as well as the clinical literature, human growth hormone has become an important topic in the field of anti-aging medicine. It is well known that the administration of human growth hormone compensates for the dwarfism syndrome in growth hormone-deficient children and growth hormone is also established as a substitution therapy for adults with pituitary deficiency. The effects mediated by growth hormone comprise an increase in muscle mass, a decrease in body fat, improved physical condition, oxygen consumption and overall quality of life, an improvement of the ratio of high-density lipoprotein to low-density lipoprotein, as well as an increase in bone density. Due to the insulin antagonistic effect of growth hormone as well as its insulin-like growth factor-1-mediated mitogenic effect, there is reason to doubt the safety of administering growth hormone outside the framework of approved indications. In an ongoing study, we are evaluating whether growth hormone and somatomedins might be of importance in the regulation of male sexual performance, including penile erection.

Adult↗
PubMed2001

Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction.

Based on the increasing knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation, which is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have recently been introduced in the treatment of erectile dysfunction. The first promising clinical data on the use of the orally active PDE5 inhibitor Sildenafil in the treatment of erectile dysfunction were accompanied by boosting research activities on cavernous intracellular signal transduction and phosphodiesterase characterization with the aid of molecular biology and protein chemistry. The presence of mRNA transcripts specific for 14 different human phosphodiesterase isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR: Three isogenes of PDEI, PDE2A and 10A, which hydrolyse cAMP as well as cGMP, the cAMP-specific PDE3A, four isogenes of PDE4, PDE7A and PDE8A, as well as cGMP-specific PDEs PDE5A and PDE9A. Using anion exchange chromatography, the activities of PDE isoenzymes 2, 3, 4, and 5 were detected in cytosolic supernatants of human cavernous smooth muscle. To date, the efficacy and safety of several next generation PDE5 inhibitors for use in the treatment of male erectile dysfunction are under evaluation in vitro and in vivo. Further research will possibly allow identification of diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

Cyclic GMP↗
PubMed2001

Central effects of sildenafil (Viagra) on auditory selective attention and verbal recognition memory in humans: a study with event-related brain potentials.

The purpose of this study was to assess possible central side-effects of sildenafil (Viagra) on attention and memory functions. Sildenafil and placebo were administered in young male subjects in a double-blind balanced cross-over design. Behavioral patterns and event-related brain potentials (ERP) were recorded in a spatial auditory attention and a visual word recognition task. While behavioral patterns did not reveal any overt effects of sildenafil, auditory ERPs were indicative of an enhanced ability to focus attention (amplitude enhancement of Nd-effect) and to select relevant target stimuli in the sildenafil condition (P3 component). In the memory task, CNS-effects of sildenafil were evident in a reduction of a negativity in the 150-250 ms range. No overt effects on behavior were observed. Nevertheless, the data reveal CNS-effects of sildenafil necessitating further studies.

Adult↗
PubMed2001

Immunocytochemical distribution of nitric oxide synthase in the human corpus cavernosum: an electron microscopical study using the tyramide signal amplification technique.

Nitric oxide has proven to be an important mediator in the relaxation of human cavernosal smooth muscle. Nevertheless, there are many inconsistencies in the literature regarding the cellular and subcellular distribution of endothelial nitric oxide synthase in the human penis. The purpose of this study was to reexamine the localization of eNOS and nNOS in the cellular anatomy of the human cavernous body by means of electron microscopical immunocytochemistry in combination with the tyramide signal amplification technique (TSA). Using specific antibodies against eNOS and nNOS, the NAPDH-diaphorase reaction and advanced protocols for fixation and staining procederes, the occurrence of NOS isoenzymes eNOS and nNOS were examined in cavernosal specimens of ten male patients who were subjected to surgery for penile deviation. eNOS immunoreactivity and NADPH-d staining was seen to be significantly present in the endothelial cells covering the cavernous spaces and in the endothelium of helicine arteries. In endothelial cells, the NADPH-d reaction product BSPT-formazan was abundantly detectable attached to membranes of the endoplasmatic reticulum and the mitochondria whereas posititve eNOS immunostaining was seen in the endothelial cells throughout their cytoplasm without any particular relation to organelles. No considerable eNOS immunoreactivity was detectable in the trabecular smooth muscle cells. nNOS staining was found in nerve fibers innervating the cavernous body and cavernosal arteries. Our results counteract the hypothesis of the cavernous smooth muscle as a local source of NO and underline the importance of an intact endothelial function for penile erection and the contribution of eNOS to this process.

Biotin↗
PubMed2001

Plasma levels of cyclic guanosine-3',5'-monophosphate in the cavernous and systemic blood of healthy males during different functional conditions of the penis.

The relaxation of cavernous arterial and trabecular smooth muscle is dependent upon the stimulation of guanylyl cyclase activity by nitric oxide (NO), which is released from nerve terminals and endothelial cells within the cavernous tissue, and the subsequent accumulation of cyclic guanosine-3',5'-monophosphate (cGMP) in the intracellular space. The present study was undertaken to determine whether or not plasma levels of cGMP in the systemic and cavernous blood of healthy male subjects change from penile flaccidity to tumescence, rigidity and detumescence. Fifteen adult healthy males were exposed to visual and tactile erotic stimuli to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein in the respective penile stages, and cGMP was determined in plasma aliquots by means of a radioimmunoassay. Mean systemic and cavernous plasma levels of cGMP in the blood samples obtained from the healthy volunteers ranged from 1.2-1.7 pmol/ ml. cGMP levels in the systemic circulation and in the cavernous blood did not change during developing erection, rigidity and detumescence. No significant differences were found between cGMP plasma levels in the systemic and cavernous blood in the different penile stages. Our results may reflect the fact that the stimulation of NO production in healthy males during sexual arousal and developing penile erection either does not yield substantial quantities of cGMP or that the rate of cGMP-extrusion from cavernous smooth muscle cells into the extracellular space accounts only for a minor fraction of plasma cGMP. Moreover, basal levels of cGMP in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection may conceal any local release of cGMP that may occur within the penile erectile tissue. Thus, we conclude that the quantification of cGMP is of no use in the evaluation of the physiologic mechanisms of penile erection in vivo.

Adult↗
PubMed2001

Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside.

Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders. We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis. The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size. Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction.

Humans↗
PubMed2001

Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence.

OBJECTIVES: To examine the functional effects of bradykinin (BK) and angiotensin II (AN II) on isolated human cavernous tissue and to detect any changes in the AN II levels in cavernous and peripheral blood samples taken from healthy volunteers at different functional conditions of the penile erectile tissue. Metabolites of the renin-angiotensin system and endothelium-derived vasoactive substances are known to be involved in the regulation of arterial vascular tone. The human corpus cavernosum (HCC), consisting of endothelial and smooth muscle cells, can be regarded as a compartment comparable to the vascular system. METHODS: The relaxing and contracting properties of BK and AN II on isolated HCC were investigated using the organ bath technique. Tissue levels of adenosine-3,5-cyclic monophosphate (cAMP) and guanosine-3,5-cyclic monophosphate (cGMP) were determined using specific radioimmunoassays, after exposing isolated HCC strips in a dose-dependent manner to BK, forskolin, and sodium nitroprusside. Blood samples were drawn simultaneously from the corpus cavernosum and cubital vein of 34 healthy volunteers at stages of penile flaccidity, tumescence, rigidity, and detumescence. Penile erection was induced by audiovisual and tactile stimulation. AN II levels were determined using a radioimmunoassay. RESULTS: In vitro, BK, forskolin, and sodium nitroprusside elicited dose-dependent relaxation of norepinephrine-induced tension of isolated HCC, and AN II evoked dose-dependent contraction of the HCC strips. The relaxing potency of BK was paralleled by its ability to elevate the intracellular levels of cAMP and cGMP. In vivo, the AN II levels in the cavernous plasma increased from 21.8 +/- 4.6 pg/mL in the flaccidity phase to 27.9 +/- 10 pg/mL in the detumescence phase. In the peripheral plasma, the AN II levels were 17.2 +/- 6.2 to 19.5 +/- 6.5 pg/mL in the respective penile stages. Thus, the mean AN II levels in the cavernous blood were about 30% higher than in the blood samples taken from the cubital vein. In the cavernous blood, the increase in the AN II plasma levels in the detumescence phase (27.9 +/- 10 pg/mL) was statistically significant. CONCLUSIONS: Our results suggest that penile cavernous smooth muscle tone is partially balanced by kinin-induced relaxation and AN II-induced contraction. Since the tissue and plasma levels of both peptides are regulated by the activity of the angiotensin-converting enzyme, there might be a rationale for the use of angiotensin-converting enzyme inhibitors in the treatment of erectile dysfunction associated with arterial hypertension.

Adult↗
PubMed2001

Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction.

OBJECTIVES: To determine the testosterone plasma levels in the cavernous and peripheral blood taken during different penile conditions from patients with erectile dysfunction (ED) and to evaluate whether these courses are different from those detected in the blood of healthy males. Although the determination of the systemic testosterone concentration (TC) has been fairly well established in the diagnostic workup of ED, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and cubital vein of 54 healthy males with normal erectile function and 46 patients with ED during the penile stages of flaccidity, tumescence, rigidity (reached by the healthy males only), and detumescence. Tumescence and rigidity were induced by audiovisual and tactile stimulation. The TC was determined by means of a radioimmunoassay. RESULTS: In the flaccid phase, the TC in the cavernous blood taken from the healthy volunteers was 2.9 +/- 1.2 ng/mL. The TC significantly increased during tumescence (4.3 +/- 1.3 ng/mL) and rigidity (4.4 +/- 1.4 ng/mL), P <0.001. In the detumescence phase, the TC decreased appreciably to 3.5 +/- 1.4 ng/mL. In the systemic blood, the increase from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1.4 ng/mL) was found to be less pronounced but, nevertheless, significant (P = 0.001). No further increase was detected during rigidity. From rigidity to detumescence, the systemic TC dropped to 4.1 +/- 1.2 ng/mL. In the patients with ED, the mean increase in systemic and cavernous testosterone levels from flaccidity (cubital vein 3.0 +/- 1.0 ng/mL, corpus cavernosum 2.6 +/- 1.0 ng/mL) to tumescence (cubital vein 3.2 +/- 1.1 ng/mL, corpus cavernosum 3.0 +/- 1.0 ng/mL) was less pronounced. Nevertheless, the course of testosterone detected in the systemic and cavernous plasma of the patients during flaccidity, tumescence, and detumescence resembled that registered in the healthy controls. In the flaccid phase, the mean cavernous TC in the healthy subjects was found to be 30% lower than the level in the peripheral blood; in the patients with ED, this difference was only 13%. CONCLUSIONS: In the healthy males, the penile erection was accompanied by an increase in the cavernous and peripheral TC. The difference between the peripheral and cavernous TC in the healthy subjects and patients with ED in the flaccid phase, when the blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone, as well as the density of testosterone receptors, in the cavernous smooth musculature.

Erectile Dysfunction↗
PubMed2001

Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction.

OBJECTIVES: To detect changes in plasma levels of angiotensin II (Ang II) under different functional conditions of the penile erectile tissue in the cavernous and systemic blood of patients with erectile dysfunction (ED) and compare them with the course of Ang II in healthy male subjects. It has been shown that the mammalian corpus cavernosum produces and secretes physiologically relevant amounts of the vasoconstrictive peptide Ang II and that intracavernosal injection of Ang II terminates penile erection in the dog. Thus, we speculated whether a dysregulation in the secretion or degradation of Ang II might contribute to the manifestation of ED. METHODS: Thirty-four healthy adult men and 48 patients with ED of either organogenic or psychogenic etiology were exposed to visual and tactile erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during the different functional conditions of the penis. Ang II plasma levels were measured using a radioimmunoassay. RESULTS: In healthy men, the Ang II levels in the cavernous plasma increased from 22.1 +/- 7.1 pg/mL in the phase of penile rigidity to 27.9 +/- 10 pg/mL in the detumescence phase. In the peripheral plasma, the Ang II levels were 17.2 +/- 6.2 to 19.5 +/- 6.5 pg/mL over the respective penile stages. The courses of Ang II registered in the patients were similar to those detected in the healthy men. In the patients and healthy men, systemic Ang II levels were found to be lower than the concentrations detected in the cavernous blood. In the group of organogenic patients, the Ang II levels during penile flaccidity in the systemic and cavernous blood were higher than those registered in the blood samples taken from the healthy men. CONCLUSIONS: Our results suggest that cavernous smooth muscle tone is, in part, balanced by Ang II-induced contraction and that Ang II might be involved in the initiation of penile detumescence in men. That Ang II plasma levels are generally elevated in the systemic and cavernous blood of patients with an organogenic etiology of ED may hint at the significance of Ang II in the pathophysiology of ED. Since the tissue and plasma levels of Ang II are regulated by the activity of angiotensin-converting enzyme, there might be a rationale for the use of angiotensin-converting enzyme inhibitors in the treatment of vasculogenic ED.

Adult↗
PubMed2001

Smooth muscle electromyography.

This article addresses smooth muscle physiology, electromechanical and pharmacomechanical coupling, computed-based interpretations, and the role of electromyography in the diagnosis of erectile dysfunction.

Discriminant Analysis↗