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Biomedical subjects

A Melman

Publications and source records attributed to A Melman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Results of surgical treatment for abnormal penile curvature: Peyronie's disease and congenital deviation by modified Nesbit plication (tunical shaving and plication).

PURPOSE: We report a modification of the Nesbit plication with partial thickness shaving instead of conventional excision of a wedge of tunica albuginea. The technique minimizes intraoperative bleeding, obviates cavernous tissue damage and improves adhesion of plicated tunical layers. MATERIALS AND METHODS: Between September 1988 and September 1994, 32 patients underwent modified plication repair of chordee secondary to Peyronie's disease (26) or congenital penile deviation (6). The results were evaluated in the spring of 1996. RESULTS: Mean age plus or minus standard deviation was 55 +/- 8.8 years for patients with Peyronie's disease and 27 +/- 6.85 years for those with congenital penile deviation. Mean duration of Peyronie's disease was 22 +/- 9 months. Eight patients complained of erectile dysfunction and penile curvature. Plication for congenital deviation (6 patients) resulted in 100% satisfaction with the surgical result. Of the 26 men with Peyronie's disease 19 (78%) reported a good to excellent outcome. With prolonged followup (1 to 5 years) 7 patients had recurrent curvature due to progression of disease, including 5 with mild curvature who were able to have intercourse, in contrast with 2 who had severe early recurrence of deformity (more than 30 degrees) within 1 year postoperatively and underwent a second modified plication with good clinical outcome. Six of 32 patients with peyronie's disease were unable to resume satisfactory coitus with a postoperative straight penis. All 6 patients had concomitant poor erections preoperatively as shown by nocturnal peniletumescence and rigidity testing and 5 of them resumed regular intercourse with intracavernous pharmacotherapy. CONCLUSIONS: Long-term results of this modified plication demonstrate excellent clinical outcome with minimal morbidity.

Adolescent↗
PubMed1997

On the putative mechanistic basis for intraoperative propofol-induced penile erections.

Propofol is an hypnotic drug used in anesthesia which was noted to induce marked vasodilation in vivo and in vitro, and to elicit intraoperative penile erections. The goal of this study was to assess the putative mechanistic basis for this later observation by confirming its action in vivo in a rat model of penile erection, as well as by studying its effects in vitro on cultured human corporal smooth muscle cells and isolated corporal tissue strips. In vivo experiments were conducted on Fisher 344 rats anesthetized with sodium pentobarbital or propofol. Intracavernosal pressure was recorded during current stimulation of cavernous nerves. A significant increase in the intracavernous pressure response was recorded at all levels neurostimulation, ranging from 1-10 mA. In vitro experiments were conducted utilizing digital imaging microscopy to assess the effects of propofol (3-12 micrograms/mL) on ET-1-induced (50 nM) intracellular Ca2+ transients [Ca2+]i in Fura-2-loaded cultured human corporal smooth muscle cells (passage 3-4) as well as to evaluate the effects of propofol on phenylephrine (PE)-induced contractile responses on isolated corporal tissue strips. With respect to the former, resting cytosolic calcium levels were not altered during preincubation with propofol alone at clinically effective concentrations (12 micrograms/mL). However, propofol produced a concentration-dependent decrease in the peak amplitude of the transient ET-1-induced (50 nM) [Ca2+]i response (P < 0.001). Preincubation of the cells with calcium free/EGTA (1 mM) buffer produced a reduction in the peak amplitude of the ET-1-induced [Ca2+]i transient (55.5 +/- 6% (n = 10 cells, P < 0.01)) which was indistinguishable from that produced by 8 micrograms/mL of propofol (53.4 +/- 5.6% (n = 12 cells, P < 0.01)). However, propofol had no effect on the histamine-induced [Ca2+]i response. Lastly, preincubation of isolated human corporal tissue strips with propofol (100-200 microM; 30 min) caused a significant diminution in the peak amplitude of the PE-induced contractile response. Taken together, these data indicate that the mechanistic basis for intraoperative penile erections observed with propofol may be related, at least in part, to altered transmembrane calcium flux through voltage-dependent calcium channels, and thus, decreased corporal smooth muscle tone.

Adrenergic alpha-Agonists↗
PubMed1997

Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat.

The rapid spread of locally restricted neural and hormonal signals among the vast array of largely inexcitable corporal smooth muscle cells is an absolute prerequisite to normal erectile function. And yet the mechanism(s) responsible for this phenomenon is not well understood. As a first step toward a more integrative understanding of erectile physiology and/or dysfunction, an 8- to 12-wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received injection of vehicle only while nine others served as sham-operated control animals. Eight STZ-diabetic animals received insulin replacement. Erectile function was assessed by evaluation of penile reflexes and monitoring of intracavernous pressure responses to both electrical stimulation of the cavernous nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous pressure responses to neurostimulation were significantly attenuated in both STZ-diabetic and subtotal pancreatectomy animals compared with age-matched control animals (P < 0.05). Penile reflexes were also significantly diminished (P < 0.05). Regression analysis revealed that diabetes-related decreases in neurostimulated intracavernous pressure responses were strongly correlated with diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88). However, there were no detectable diabetes-related differences in pharmacological erections induced by intracavernous papaverine or nitroglycerin injection. Northern analysis revealed a marked diabetes-related increase in the amount of connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement partially restored (attenuated the loss of) synaptophysin immunoreactivity and maintained neurostimulated intracavernous pressure responses to control levels while having no effect on penile reflexes. These observations may have important implications to the understanding of erectile physiology as well as the etiology of diabetes-related erectile dysfunction.

Animals↗
PubMed1996

Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells.

Gap junction-mediated communication is required for normal cellular growth and differentiation. As cancer is thought to be a manifestation of the breakdown of cell-cell communication, with the concomitant loss of growth control, it would be expected that alterations in the primary structure, processing, oligomerization or trafficking of connexin (cxn) molecules would have a profound effect on the neoplastic process. Here we a present a preliminary immunohistochemical and molecular analysis of cxn 43 expression in prostatic epithelial cells from resected human tissue. Our data indicate that benign prostatic epithelial cells express cxn 43 protein, but that this expression is diminished in more advanced, anaplastic cancer cells. These data suggest that decreased connexin expression is not involved in the initiation of prostate cancer, but rather occurs during the progression of the disease.

Adenocarcinoma↗
PubMed1996

Forskolin: a promising new adjunct to intracavernous pharmacotherapy.

PURPOSE: To evaluate the utility of forskolin as a potentially novel intracavernous therapy. MATERIALS AND METHODS: Forskolin- and prostaglandin E1 (PGE1)-induced intracorporal pressure changes were evaluated in vivo by cavernosometry performed on 2 male mongrel dogs, while systemic pressure changes were simultaneously monitored. Forskolin- and PGE1-induced intracellular cAMP accumulation was measured in vitro on homogeneous explant cultures of canine corporal smooth muscle cells. RESULTS: Forskolin and PGE1 elicited concentration-dependent increases in cAMP accumulation in cultured canine corporal smooth muscle cells. Forskolin and PGE1 also elicited concentration-dependent increases in both the magnitude and duration of intracorporal pressure, up to a maximum of 80 to 90% of mean arterial pressure. Furthermore, the presence of threshold concentrations of forskolin was shown to significantly augment the activity of PGE1 both in vitro (increased cAMP) and in vivo (increased pressure). Moreover, there were no detectable systemic effects following the intracorporal injection of forskolin or a mixture of forskolin and PGE1. CONCLUSIONS: These observations suggest that the use of forskolin, alone or in combination with other drugs that increase intracellular cAMP levels, might represent an attractive opportunity for improved and more rational development of next generation intracavernous pharmacotherapeutic agents.

Alprostadil↗
PubMed1996

Identification of a down-regulated mRNA transcript in corpus cavernosum from diabetic patients with erectile dysfunction.

Fifty per cent of men with diabetes have erectile dysfunction. Previous studies demonstrated that cultured smooth muscle cells from corpus cavernosum display significantly altered K+ channel function, PGE-induced cAMP accumulation, and endothelin-1 induced Ca2+ mobilization that are consistent with the pathophysiology of erectile dysfunction. Since defects in signal transduction frequently lead to altered gene expression, we examined differences in gene expression in corporal tissue excised from three diabetic patients with erectile dysfunction function and one patient with neurogenic erectile dysfunction. Using differential display, we identify a transcript expressed in tissue derived from the patient with impotence secondary to a radical prostectomy, but which was greatly reduced or absent in corporal tissue from all three diabetic patients examined. DNA sequence analysis indicates that this transcript has no significant homology to sequences presently deposited in the GenBank database. This suggests that altered gene expression may play a significant part in the etiology of erectile dysfunction.

Base Sequence↗
PubMed1996

The correlation between the new RigiScan plus software and the final diagnosis in the evaluation of erectile dysfunction.

PURPOSE: The computer generated recordings for 2 nights in 40 patients studied with the RigiScan device were reevaluated using the new RigiScan Plus software to test its value in improving the discrimination between psychogenic and organic erectile dysfunction. MATERIALS AND METHODS: Each man was evaluated for erectile dysfunction with a detailed medical and sexual history, physical examination, biothesiometry, plethysmography, 2 nights of ambulatory RigiScan monitoring and a psychological evaluation that usually included a private interview with the sexual partner. At the conclusion of evaluation each patient was broadly classified as having organic or psychogenic erectile dysfunction. The RigiScan reports were initially independently analyzed without the investigator's knowledge of the final diagnosis by determining the single best erectile event, with a minimal cutoff value of 60% erection for 5 minutes as necessary to be considered normal and the sum of measurements from the 2 nights. The original reading and final diagnosis were correlated. At this point the data were processed with the new RigiScan Plus software using 2 new measurements: 1) rigidity activity units and 2) tumescence activity units at the base and tip of the penis, and the results were correlated with the final diagnosis. RESULTS: Evaluation of the single best event again showed that tip rigidity was the best single predictor if the diagnostic criteria were modified to 70% tip rigidity for 5 minutes with an estimate of correct classification of 92.5%. Nearly the same accuracy was obtained by base single event rigidity, tip rigidity and base tumescence activity units (each 90%). The summary analysis of all erectile events during the 2 nights of evaluation that had a low correlation with the final diagnosis using the original software showed that the best overall predictor of final diagnosis was tip tumescence activity units (92.5%), followed by base rigidity and tumescence activity units (each 90%). CONCLUSIONS: The RigiScan Plus software introduced 4 new parameters that facilitate interpretation of the RigiScan data. The new software did not improve the correlation with the final diagnosis compared to the subjective single best event analysis but added new objective parameters, measured and displayed by the software, that facilitate use of the data by the physician.

Diagnosis, Differential↗
PubMed1995

Accuracy of the initial history and physical examination to establish the etiology of erectile dysfunction.

OBJECTIVES: Because of its implications for possible therapy, the ability to establish a diagnosis of erectile dysfunction (ED) solely on the basis of history and physical examination has been a matter of controversy. The determination of the etiology of ED based on history and physical examination is evaluated in this present study. METHODS: Consecutive patients presenting for evaluation of ED were evaluated by careful history, physical examination, psychologic evaluation, and RigiScan monitoring. They were then stratified into either organic or psychogenic groups based on each of these modalities. These diagnoses were then compared to a final diagnosis obtained through additional testing. RESULTS: History and physical examination had a 95% sensitivity but only a 50% specificity in diagnosing organic ED. The accuracy rates of history and physical examination in diagnosing ED were 80% and 60%, respectively. CONCLUSIONS: A multifaceted comprehensive approach is required to evaluate fully and to diagnose ED.

Adult↗
PubMed1995

Follow-up of vacuum and nonvacuum constriction devices as treatments for erectile dysfunction.

Of 20 men evaluated for erectile dysfunction (ED) for whom vacuum erection devices or constriction bands were recommended, only four experienced improvement of their erectile function by using the specific suggested method. Although use of a simple constriction band mechanism (e.g., a rubber band wound tightly around the penis) for men with brief erectile capacity has been described as a viable treatment, only one of five men who tried using it achieved any success. Three of six men who used a vacuum erection device were helped by it, particularly the men who suffered from only partial ED. Most patients did not follow through with the recommended treatment and stopped sexual activity, or belatedly returned for intracavernosal injections. The interviews revealed the pervasive influence of shame and demoralization regarding erectile problems, the importance of evaluation and treatment follow-up, and the necessity for careful, explicit, extensive, and concrete explanations and instructions regarding treatment options.

Adult↗
PubMed1995

Characterization of nitroglycerine-induced relaxation in human corpus cavernosum smooth muscle: implications to erectile physiology and dysfunction.

The importance of the nitric oxide--guanylate cyclase--cGMP system in modulating corporal smooth muscle tone and penile erection has been amply demonstrated. The goal of these studies was to evaluate the possibility that age- or disease-related alterations in human corporal smooth muscle responsivity to activation of this pathway might play a role in the etiology of erectile dysfunction. Thus, we utilized a previously described heuristic model to assess the kinetic and steady-state characteristics of relaxation of precontracted isolated corporal tissue strips elicited by nitroglycerine (NTG). Studies were conducted on corporal tissue strips excised from 26 patients with organic erectile dysfunction, and 7 patients with documented erections. For the purposes of statistical analysis the impotent patient population was stratified into two age groups (A, < or = 59 years; B, > or = 60 years) and further subdivided into two diagnostic categories, diabetic and nondiabetic patients, respectively. In approximately 75% of precontracted corporal tissue strips derived from impotent patients (contracted to approximately 75% of maximum with phenylephrine), the NTG-induced response was biphasic, consisting of a rapid relaxation response that reached steady state before onset of a more slowly developing regaining of tension, termed the desensitization response. In contrast, a biphasic response was observed much less frequently (approximately 30%) in corporal tissue strips derived from a potent patient population (p < 0.0001). Statistical analysis revealed significant heterogeneity among corporal tissue strips derived from patients with organic erectile dysfunction, with respect to both the kinetic and steady-state characteristics of the NTG-induced relaxation and desensitization responses. In particular, the maximal rate constant for both NTG-induced relaxation (krelmax; p < 0.01) and desensitization (kdes; p < 0.03) responses was significantly greater in corporal tissue strips excised from diabetic than nondiabetic patients. Furthermore, the EC50 for NTG-induced relaxation of precontracted corporal smooth muscle strips from potent patients (approximately 25 nM) was 0.90 log unit less than that for equivalently contracted corporal smooth muscle strips derived from impotent patients (approximately 180 nM; p < 0.03). Such observations suggest that alterations in corporal smooth muscle responsivity to activation of the guanylate cyclase--cGMP pathway, per se, may be a characteristic of organic erectile dysfunction. In the absence of compensatory changes in other vasodilatory mechanisms, this may contribute to incomplete corporal smooth muscle relaxation and the etiology of erectile dysfunction in some patients.

Adult↗
PubMed1995

The epidemiology of erectile dysfunction.

During the last two decades, significant advances have been made in the understanding of male sexual dysfunction. Concomitantly, a marked increase in both clinical and research activity in the field of male erectile dysfunction has led to a better evaluation and more treatment options. The prevalence and incidence are dependent on the definitions used, the diagnostic tolls, and the treatment options. Using standard definitions as suggested by the NIH Consensus Conference and improving our diagnostic and treatment options will have a major impact on the epidemiology of ED. A summary of the risk factors for ED is presented in Table 3. Still more epidemiologic research is essential to further understand the distribution as well as the prevalence of ED in certain ethnic groups, chronic conditions, and as a result of surgery and trauma. These studies will help us improve our diagnostic skills as well as our therapeutic options.

Chronic Disease↗
PubMed1995

Penile revascularization.

Penile revascularization surgery to correct penile vascular insufficiency has undergone several modifications since its introduction. Further improvement in the surgical success rate will be achieved with improved understanding of erectile physiology, diagnostic methodology, and both microsurgical and radiological techniques.

Adult↗
PubMed1995

Endothelin-1 as a putative modulator of erectile dysfunction: I. Characteristics of contraction of isolated corporal tissue strips.

Normal erectile physiology is heavily dependent on a delicate balance between the effects of endogenous vasoconstricting and vasorelaxing hormones on the tone of the corporal smooth muscle. Recent studies indicate that endothelin-1 (ET-1) is present and physiologically active in the human corpora. The primary goal of the present investigation was to further define the role of ET-1 in corporal physiology and to ascertain whether it might play a role in augmenting corporal tone in vivo, as reported in other vascular tissues. Thus, we conducted pharmacological studies of ET-1-induced steady-state contractions in isolated human corporal smooth muscle strips to determine if there were any detectable age- or diabetes-related alterations in ET-1-induced contractions. For statistical analysis, the patient population was divided into 2 age groups, A (< or = 59 years of age; = 11 patients) and B (> or = 60 years of age; n = 7 patients), and further subdivided into 2 diagnostic categories, diabetic (n = 7 patients) and nondiabetic (n = 11 patients). Construction of cumulative concentration response curves (CRCs) for ET-1-induced contractions revealed characteristically slow onset and long-lasting responses. Endothelin-1 CRC data were computer fit to the logistic equation to derive Emax (calculated maximal response), pEC50 (negative logarithm of the concentration that elicits one-half of the calculated maximal response) and slope factor (n) values. Two-factor analysis of variance revealed no detectable age- or diabetes-related alterations, nor any age-diabetes interaction in any of the logistic parameters. Furthermore, logistic analysis of ET-1 CRC data on 14 isolated corporal tissue strips derived from 3 potent patients with documented spontaneous erections revealed no differences in ET-1 contractility from that observed for patients with organic erectile dysfunction. Importantly, despite an apparent absence of age- or diabetes-related alterations in ET-1-induced steady-state contractions, preliminary studies demonstrated that coadministration of the alpha 1-adrenergic agonist phenylephrine and ET-1 produce much greater contractile responses than those observed in the presence of phenylephrine (PE) alone. Moreover, the magnitude of the augmentation was precisely that predicted by a model for simple additivity of agonist effects. Such observations suggest that the physiological relevance of ET-1 to corporal physiology may be related to its ability to augment the contractile responses of other vasomodulators present in the human corpora, in particular, perhaps modulating the contractile responses to sympathetic activity.

Diabetes Mellitus↗
PubMed1995

An analysis of the Maxi-K+ (KCa) channel in cultured human corporal smooth muscle cells.

Previous studies have demonstrated that cultured corporal smooth muscle cells have prominent outward K currents composed of several different K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteristics of the most predominant of these channel subtypes, the Maxi-K+ (KCa) channel, and (2) to compare KCa channel behavior in cultured corporal smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivided into two broad diagnostic categories: Group 1: 4 patients without evidence of organic disease of the corpus cavernosum, 3 of whom had documented erections; and Group 2: 4 patients with organic erectile dysfunction. Consistent with previous observations, 3 different K channel subtypes were detected in both patient populations, with corresponding conductances of 180, 100 and 40 pS, respectively. The approximately 183 pS channel was identified as the KCa channel based on its selective permeability to K+ and the fact that its open probability was modulated by both membrane potential and intracellular calcium levels. Specifically, the relative permeability of the 183 pS KCa channel to K+, Rb+, and NH4+ was 1.00:0.64:0.46. The channel was virtually impermeable to Na+ and Li+ (relative permeability < 0.02). In addition, the KCa channel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacological studies using the K channel blocker tetraethylammonium ion (TEA) revealed that the sensitivity of KCa channels to TEA inhibition (as judged by the [TEA] required to block one-half of the outward whole cell current induced by a 90 mV depolarizing pulse) in cells from Group 1 patients was 1.05 +/- 0.22 mM. (n = 10 cells), while in sharp contrast the observed value for cells from Group 2 patients was 12.7 +/- 3.8 (n = 9 cells). The difference between the two groups was highly significant. These observations confirm and extend our previous studies to suggest that the KCa channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/regulation of KCa channels may be an important feature of organic erectile dysfunction. As such, altered KCa channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, possibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone.

Calcium↗