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Biomedical subjects

J Rehman

Publications and source records attributed to J Rehman.

35 records · Page 2Linked to original sources

Intracavernous pressure responses to physical and electrical stimulation of the cavernous nerve in rats.

OBJECTIVES: To better define the techniques of nerve-sparing prostate dissection that would result in preservation of erectile function, we characterize the effects of physical pressure on the prostate and cavernous nerve, electrical stimulation of the cavernous nerve, and pharmacologic manipulations on intracavernous pressure (ICP) in normal and diabetic rats. METHODS: Fischer-34 rats, both normal and diabetic, underwent dissections that isolated the cavernous bodies and cavernous nerves. Cavernous body pressures were characterized during surgical manipulation, during electrical stimulation of the cavernous nerves, and following papaverine hydrochloride injection. RESULTS: In normal rats, baseline cavernous pressures ranged from 5 to 15 cm H2O (mean 12.29). In diabetic rats, the baseline pressure was significantly lower (3 to 7.5 cm H2O). Lateral nerve displacement caused ICP to rise to approximately 35 cm H2O in normal rats, but only to 20 cm H2O in diabetic rats. Electrostimulation resulted in cavernous pressure increases of 10-fold from baseline in normal rats and sevenfold from baseline in diabetic rats. ICPs were not disturbed appreciably with nerve-sparing dissection techniques. Neurotomy resulted in declines in baseline cavernous pressures in all rats. Electrostimulation of the distal end of a severed nerve resulted in pressure rises to 50% of those observed in rats with intact cavernous nerves. Intracavernous papaverine injection before or after nerve stimulation masked subsequent (expected) pressure changes. CONCLUSIONS: A change in cavernous pressure is a sensitive indicator of cavernous nerve manipulation. Both cavernous pressure measurements and electrostimulation of cavernous nerves may aid surgeons during radical prostatectomy.

Animals↗

Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study.

OBJECTIVES: Multiple conservative therapies for the treatment of Peyronie's disease have been offered with variable and poor response rates. Calcium channel blockers have been shown in vitro and in vivo to inhibit secretion and synthesis of extracellular matrix, including collagen, glycosaminoglycans, and fibronectin, as well as causing increased collagenase and anti transforming growth factor-beta activity. Calcium antagonists, including verapamil, are effective in stimulating the remodeling and degradation of extracellular matrix in tissue by altering the metabolic pathways of fibroblasts. Recently, a pilot study (1994) showed preliminary promising results in treating plaque caused by Peyronie's disease. This randomized single-blind placebo-based study (1994 to 1996) was undertaken to confirm the hypothesis. METHODS: In this randomized single-blind study, 14 patients completed the study and were divided into two groups: the verapamil treatment group (n = 7) or the control saline group (n = 7). Verapamil or saline was injected directly into the Peyronie's plaque once a week for 6 months. Patients were evaluated before and after treatment with duplex ultrasound to confirm the extent of the lesion and to measure volume of the plaque, and by interview and mailed questionnaire 3 months after treatment. Patients being treated with oral calcium antagonists were excluded from the study. RESULTS: A decreased plaque volume was measured in 57% of the verapamil-treated men versus 28% in the control group (P <0.04). Penile curvature demonstrated an improvement trend of 37.71 +/- 9.3 degrees to 29.57 +/- 7.3 degrees in the verapamil-treated patients, but the difference was not significant (P <0.07). Plaque softening was noted in all patients treated with verapamil. There was significant objective improvement in plaque-associated penile narrowing in all patients in the verapamil group. Subjective plaque-associated erectile dysfunction (quality of erection) showed improvement in 42.87% of the verapamil group versus none in the control group (P <0.02). There was no local or systemic toxicity except for an occasional ecchymosis/bruise at the injection site. After a positive clinical response, plaque size, penile angulation, and symptoms continued to improve. Decrease in plaque size was noted in each of the responders in the first 3 months. CONCLUSIONS: This randomized single-blind study suggests that intralesional injection of calcium channel blocker may be a reasonable approach in some selected patients for the treatment of Peyronie's disease with noncalcified plaque and penile angulation of less than 30 degrees. Patients whose plaque failed to respond to intralesional verapamil therapy within 3 months or whose angulation was greater than 30 degrees at presentation were more likely to benefit from surgery.

Adult↗

Early endoscopic realignment as primary therapy for complete posterior urethral disruptions.

We assessed the outcome of early endoscopic realignment of posterior urethral disruptions. We evaluated six patients who underwent early or delayed endoscopic realignment for the disrupted posterior urethra over a 3-year period. C-Arm fluoroscopy guidance and orientation in two planes were used as necessary. Potency, restructure rates, and continence were assessed in addition to hospital length of stay, intraoperative blood loss, and uroflow. The collective results of ten publications were also reviewed. In the present study, all of the six patients were continent. One had diminished erectile capability, and four required subsequent internal urethrotomies. Evaluation of the cumulative data (including the present study) showed an overall 9% incontinence rate, 60% potency rate, and 54% restricture rate. Endoscopic realignment of the disrupted posterior urethra is a minimally invasive procedure with results comparable to those of open delayed urethroplasty. Early and delayed repairs have been applied with similar results, the former being advocated in patients who are medically and orthopedically stable. Hospital stay, loss of work, morbidity, and related complications are also markedly decreased with early endoscopic realignment.

Adolescent↗

Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function.

The Ca2+-sensitive K+ channel (maxi-K+) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: 1) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K+ channel, and 2) to determine whether transfection of the maxi-K+ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMVbeta/Lac Z DNA in 10-wk-old rats resulted in significant incorporation and expression of beta-galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N = 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N = 5) and 2 mo (N = 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N = 2) and 4 mo (N = 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.

Animals↗

Dynamic exercise leads to an increase in circulating ICAM-1: further evidence for adrenergic modulation of cell adhesion.

Acute mental and physical stress lead to a marked lymphocytosis, with circulating natural killer cell numbers showing the most prominent increase. Many studies have linked these acute stress effects on lymphocytes with an increase in catecholamine levels. However, the molecular mechanisms which mediate this redistribution of lymphocytes from lymphocyte reservoirs into the circulation remain unknown. We hypothesized that this form of lymphocytosis was in part due to shedding of cell adhesion molecules from the cell surface and a subsequent detachment of lymphocytes adhering to the vascular endothelium in lymphocyte reservoirs. In this study, healthy human volunteers (n = 12) were exercised on a treadmill until exhaustion. The circulating levels of the soluble cell adhesion molecules ICAM-1 and E-Selectin were determined by ELISA. The subjects were then randomly assigned to treatment with either propranolol or metoprolol and repeated the exercise protocol after 1 week of treatment. Prior to drug treatment, soluble ICAM-1 levels rose from 258 +/- 19 to 321 +/- 28 ng/ml following exercise and returned to approximate baseline levels of 263 +/- 22 ng/ml after 1 h of rest. This highly significant effect of exercise on circulating ICAM-1 levels (p < .005) was mitigated after treatment with the beta-adrenergic antagonists. Soluble E-Selectin levels were not significantly affected by exercise. These results suggest that dynamic exercise leads to shedding of the cell adhesion molecule ICAM-1 via adrenergic mechanisms. We believe that these findings will contribute to the understanding of how physical and mental stress modulate lymphocyte migration and adhesion.

Adrenergic beta-Antagonists↗

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↗

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↗

Nitrate, a nonphotic signal for the circadian system.

Recent advances in circadian biology have brought insights into the molecular mechanisms involved in the generation of circadian rhythmicity. However, little is known about the relationship between these molecular oscillators and the organism's temporal adaptation to complex daily environmental changes. We have studied the effects of nutrients on the circadian system of a marine unicellular alga and found that nitrate influences all three canonical properties of circadian rhythmicity: amplitude, phase, and period. The effects of nitrate are part of a complex feedback loop involving both circadian input and output. These new aspects of circadian nutrient metabolism have important implications for our understanding of the ecological significance of circadian programs.

Animals↗

Inhibitors of serine/threonine phosphoprotein phosphatases alter circadian properties in Gonyaulax polyedra.

Protein serine/threonine phosphatases were implicated in the regulation of circadian rhythmicity in the marine dinoflagellate Gonyaulax polyedra based on the effects of three inhibitors specific for protein phosphatases 1 and 2A (okadaic acid, calyculin A, and cantharidin). Chronic exposure to okadaic acid resulted in a significant period lengthening, as measured by the bioluminescent glow rhythm, whereas cantharidin and calyculin A caused large phase delays but no persistent effect on period. Short pulses of the phosphatase inhibitors resulted in phase delays that were greatest near subjective dawn. Unlike 6-dimethylaminopurine, a protein kinase inhibitor, okadaic acid, calyculin A, and cantharidin did not block light-induced phase shifts. The inhibitors tested also increased radiolabeled phosphate incorporation into Gonyaulax proteins in vivo and blocked protein phosphatase 1 and 2A activities in Gonyaulax extracts. This study indicates that protein dephosphorylation catalyzed by protein serine/threonine phosphatases is necessary for proper functioning of the circadian system.

Animals↗

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↗

Sexuality and aging.

Because aging is frequently associated with medical conditions likely to impair sexual performance, there is a tendency to view sexual changes in older men as the result of pathology, overlooking the effect of natural processes of aging in sexuality. This article discusses the sexual responses in the aging male, the physiologic aspects of aging male sexuality, psychologic aspects of aging and sexuality, studies on aging male sexuality, a psychobiological investigation of healthy aging men, medical causes of erectile dysfunction in elderly men, and the effect of medications on the sexual functioning of aging men.

Aged↗

Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat.

In patients who recover erectile function after radical prostatectomy (with preservation of at least 1 neurovascular bundle), a recovery time of 6 to 18 months is not uncommon. As this is also the usual time required for regeneration of spinal nerves, we believe that regeneration of cavernous nerves, partially damaged inadvertently, may be responsible. In a rat model, we examined the long-term effect of unilateral and bilateral cavernous nerve transection on the nonadrenergic/noncholinergic (NANC) nervous system and erectile function. In 31 rats, nitric oxide synthase (NOS), the enzyme that catalyzes nitric oxide production, was identified in penile nerve fibers from a mid-shaft segment with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and antibody to neuronal NOS. Animals were divided into three groups: 5 rats underwent pelvic exploration without transection of cavernous nerves (sham group); 13 rats underwent unilateral neurotomy of a 5-mm. segment of the cavernous nerve; and 13 rats underwent bilateral neurotomy. After bilateral ablation, the NOS-positive nerve fibers were significantly decreased at 3 weeks and remained so at 6 months; no erectile response could be elicited by pelvic nerve stimulation. After unilateral ablation, the NOS-positive nerve fibers were similarly decreased on the side of the neurotomy at 3 weeks, but by 6 months the number had increased significantly and approximated the level on the contralateral side. Furthermore, electrostimulation of the intact side induced a greater intracavernous pressure response at 6 months than at 3 weeks (N.B. the rat has an incomplete septum). Fibers positive for NOS were also identified in the dorsal nerve. The staining pattern diminished as rapidly and significantly on the side of neurotomy as in tissue from the corpus cavernosum. However, regeneration was not seen. To our knowledge, this is the first demonstration of regeneration of NOS-containing nerves after cavernous nerve neurotomy. Our findings support the reports by others that unilateral nerve-sparing is sufficient to preserve erectile function.

Amino Acid Oxidoreductases↗

[Cellular mechanisms of circadian clocks].

The mechanisms of the biological clock are today being investigated in single neurons in cell culture or in unicellular and in other microorganisms. The results show that all components of this "endogenous clock" can be found at the cellular level. The cellular circadian program is controlled by a complex system of biochemical reactions, which can contain more than one circadian pacemaker and which comprises several feed-back loops at the input and the output side. This complex temporal program is a prerequisite for specialization and survival within the chrono-ecological niches of the "temporal space" day. It enables organisms on the one hand to adaptively react to environmental changes and thereby reaching transient independence of the external, physical time course; on the other side, it ensures that the endogenous day never runs out of synchrony with the solar day of the environment.

Animals↗

Is colchicine effective in Peyronie's disease? A pilot study.

OBJECTIVES: The treatment of Peyronie's disease with oral or topical agents has not been entirely satisfactory. In this pilot study, we hypothesized that colchicine, known to induce collagenase activity and decrease collagen synthesis, might be an ideal agent in the treatment of Peyronie's disease. METHODS: Colchicine was administered orally for 3 to 5 months to a group of 24 previously untreated patients with Peyronie's disease. RESULTS: Peyronie's plaque decreased or disappeared in 12 of the 24 patients, 7 of 9 patients with painful erections reported significant relief, and penile curvature was improved in 7 of 19 cases. Erectile status, narrowing of the penis, and accompanying Dupuytren's contracture did not change in any of the cases. CONCLUSIONS: Although this pilot study shows some promising results of the use of colchicine in the treatment of Peyronie's disease, the ultimate usefulness of this agent will be determined only by a prospective double-blind clinical study.

Aged↗

Studies on glycosylated plasma proteins in diabetic patients.

The level of glycosylated haemoglobin in the blood is considered as an index of long term blood glucose levels in diabetic patients. Glycosylation of structural proteins also occur. The present study describes the levels of glycosylated blood proteins (nonenzymatic) and blood glycoproteins (enzymatic glycosylation) in four groups of diabetic patients (n = 80) as well as non-diabetic control subjects (n = 20). The patients were divided according to the treatment they received. Glycosylated haemoglobin, glycosylated plasma proteins, fasting plasma glucose, hexosamine, sialic acid and mucoproteins were measured in each subject. All of these measurements were significantly increased in diabetic patients however, glycoproteins were not significantly correlated with glycosylated haemoglobin or fasting glucose.

Blood Glucose↗

Laparoscopic repair of diaphragmatic defect by total intracorporeal suturing: clinical and technical considerations.

OBJECTIVE: The use of laparoscopy in urology is increasing. Tumor of the kidney or adrenal gland and, in some cases, metastatic disease can involve the diaphragm. We describe the application of laparoscopic suturing techniques in the case of diaphragmatic involvement with a renal tumor. METHODS: After resection of the tumor and a small area of the diaphragm, a chest tube was placed under laparoscopic guidance. The tube was kept clamped until the end of the procedure. Decreasing intraabdominal pneumoperitoneum pressure made suturing easier with less tension on the edges of the diaphragmatic incision. Nonabsorbable interrupted horizontal mattress sutures were placed to close the diaphragmatic defect. RESULTS: The repair was uneventful; no intraoperative complications occurred. Extubation was done at the end of the procedure in the operating room. The chest tube was removed on postoperative day 2, and the patient was discharged on postoperative day 3. CONCLUSIONS: Laparoscopic repair of the diaphragm should be commensurate with traditional open surgical principles. In this regard, it is essential that surgeons interested in performing "advanced" laparoscopic oncologic surgery become facile in laparoscopic suturing.

Diaphragm↗