Benign prostatic hyperplasia.
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Biomedical subjects
Publications and source records attributed to C C Carson.
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Widespread clinical use of H2 antagonists for peptic ulcer disease has been associated with reports of impotence. Histamine is a vasoactive amine which is endogenously produced in many organs including the penis. To date, 3 histamine receptor subtypes (H1, H2 and H3) have been identified. However, the role and function of histamine in the corpus cavernosal physiology are poorly understood. This study evaluates the in vitro functional characteristics of the 3 histamine receptor subtypes in the isolated corpus cavernosal strips from New Zealand White rabbits. The isometric responses to histamine and specific histamine receptor subtype agonists were assessed, following cyclooxygenase (indomethacin, 10(-5) M.), adrenergic (guanethidine, 5 x 10(-6) M.) and cholinergic (atropine, 5 x 10(-6) M.) blockade, at resting tension and after submaximal precontraction with norepinephrine (NE, 2 x 10(-5) M.). Histamine (10(-8) M. to 10(-3) M.) produced concentration-dependent contraction from basal and precontracted states and did not relax precontracted tissue. The H1 agonist, 2-(2-thiazolyl)ethylamine (10(-8) M. to 10(-3) M.), produced a contractile response from both basal and precontracted states, while the corporal tissue did not respond to either dimaprit, an H2 agonist (10(-8) M. to 10(-5) M.) or R(-)-alpha-methyl-histamine, an H3 agonist (10(-8) M. to 10(-5) M.). The response to histamine was progressively attenuated by an H1 antagonist (mepyramine; 10(-8) M. to 10(-5) M.), while neither an H2 antagonist (cimetidine; 10(-4)M.) nor an H3 antagonist (thioperamide; 10(-4)M.) had any inhibitory effects. H1 antagonism enhanced relaxation induced by electrical field stimulation (neurally mediated). Such relaxation increased after preincubation with 10(-6) M. or greater of mepyramine (p < 0.05). This study suggests that the principal histamine receptor subtype that mediates smooth muscle cell contraction in the corpus cavernosum is the H1 subtype. Since histamine H1 receptor antagonism increased NANC neurally mediated corporal relaxation, it possesses potential as an intracavernosal pharmacotherapeutic agent for the treatment of erectile dysfunction. This study, therefore, strongly indicates that H2 receptor antagonists are unlikely to have direct effects on penile erection.
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The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC-mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p < 0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p < 0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p < 0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p < 0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO.
Hel-N1, a human RNA-binding protein, shares significant homology with Drosophila protein ELAV, which is essential for fly neuronal development. Hel-N1 has been shown to bind in vitro to 3' untranslated regions of mRNAs encoding c-myc, c-fos, granulocyte/macrophage colony-stimulating factor, and transcriptional repressor, Id. We report that Hel-N1 and a related form, Hel-N2, are expressed in human medulloblastoma cells, but their ratio differs significantly from that in adult brain and fetal brain. Selection of RNA targets from randomized combinatorial libraries yielded (A+U)-rich consensus sequences for both Hel-N1 and Hel-N2. As a means to identify cellular RNA targets for these proteins, we devised combinatorial shape libraries representing naturally derived 3' untranslated regions and were able to select a structurally related subset of transcripts that bound to Hel-N1. Approximately 10% of the proteins encoded by these subset mRNAs were identifiable in the data bases and most are implicated in cell growth regulation. This approach provides a means to gain access to novel genes expressed in various cell types by partitioning mRNAs containing common sequence elements using RNA-binding proteins.
Carbon monoxide has been proposed as a possible neurotransmitter because of its ability to bind to the iron atom of the heme of guanylyl cyclase, which is similar to that of nitric oxide. To determine whether carbon monoxide exerts an effect on the penis, strips of rabbit corpus cavernosum were mounted in an organ bath for isometric tension studies and the effect of zinc deuteroporphyrin, an inhibitor of heme oxygenase which metabolizes hemoprotein and releases carbon monoxide, on relaxation induced by electrical field stimulation (neurally mediated) was determined. Also observed was relaxation induced by electrical field stimulation after incubation with atropine and guanethidine to isolate nonadrenergic noncholinergic neurotransmission. Zinc deuteroporphyrin (10(-6) M, 10(-5) M, 10(-4) M and 3 x 10(-4) M) did not affect relaxation induced by electrical field stimulation in the absence or presence of guanethidine and atropine. Therefore, it appears that carbon monoxide does not contribute to neurally mediated relaxation of the rabbit corpus cavernosum.
To our knowledge we report the first case of primary adenocarcinoma of the penis. After extensive evaluation to rule out metastatic disease from other sources, partial penectomy for primary adenocarcinoma of the penis was performed. Select histological stains of the tumor failed to reveal an extra penile origin.
In an effort to characterize the changes in penile vasculature that occur following penile vein ligation, we performed pharmaco-cavernosometry and pharmaco-cavernosography on 20 patients after penile vein ligation for comparison with preoperative studies. Three patients with return of erectile function underwent repeat study: 2 were completely normal and 1 had a mild leak from the deep dorsal vein. The remaining 17 patients had continued complaints of erectile impairment. Of these studies 4 showed no evidence of venous leakage, 11 identified a new site of leakage (7 corporo-spongiosal shunts, 2 crural veins and 2 with multiple sites of involvement) and 1 revealed persistent leak through the proximal stump of the resected deep dorsal vein, while 1 patient had an iodine allergy and underwent pharmaco-cavernosometry only. A repeat study in the latter patient showed flow volumes consistent with continued venous leakage. In summary, penile vein ligation appears to be effective at correcting venous leakage noted on cavernosography. However, new sites of leakage frequently appear postoperatively. A corporo-spongiosal shunt was the most frequent site of recurrent venous leakage. A surprisingly high percentage of patients with continued complaints of erectile dysfunction following penile vein ligation demonstrate no venous leakage on subsequent pharmaco-cavernosography.
Hypercholesterolemia and other vascular risk factors for atherosclerosis are commonly associated with impotence. To characterize cavernosal smooth muscle reactivity in hypercholesterolemia, we performed isometric tension studies (with norepinephrine, acetylcholine, papaverine and electrical field stimulation) on isolated strips of corpus cavernosum from rabbits fed a 1% cholesterol diet. To assess the impact of cholesterol reduction, a group of rabbits was fed a cholesterol diet for 4 weeks and was then returned to a normal diet for 4 weeks before testing. Potential structure-function relationships were delineated by ultrastructural evaluation with transmission electron microscopy (TEM). All forms of cavernosal relaxation, including papaverine relaxation, were impaired with hypercholesterolemia, and norepinephrine contraction was augmented. In addition, ultrastructural evidence of an early atherosclerotic process in the cavernosal sinusoids was detected. Importantly, reduction of elevated serum cholesterol normalized cavernosal relaxation, including that of papaverine, and decreased the sensitivity to norepinephrine, thereby suggesting that cavernosal smooth muscle dysfunction in hypercholesterolemia is reversible.
PURPOSE: Diabetes mellitus is a known risk factor for accelerated atherosclerosis and for postangioplasty restenosis. METHODS: This study examines the effect of chronic, uncontrolled, alloxan-induced diabetes on the structure and vasomotor function of vein bypass grafts in 20 male New Zealand white rabbits with diabetes and in 10 controls. After 8 weeks of diabetes, a common carotid vein bypass graft was performed. Four weeks after operation, vein grafts and contralateral jugular veins were harvested. RESULTS: Diabetes induced a twofold increase in the vein graft intimal thickness compared with control. There was no change in medial thickness. Electron microscopy of the vein grafts in diabetes revealed intercellular gaps in the endothelium lining and abnormal endothelial cell junctions compared with controls. Diabetes significantly increased the maximal contractions generated in vein grafts to all contractile agonists tested without any change in sensitivity. CONCLUSIONS: This study demonstrates that diabetes alters endothelial cell structure and increases the development of intimal hyperplasia with increased maximal contractility in vein grafts and therefore suggests that the vein grafts in diabetes are more susceptible to early stenosis.
It is known that penile erection is mediated primarily through the release of a nonadrenergic noncholinergic (NANC) neurotransmitter which has been recently identified as nitric oxide (NO). To evaluate whether the endothelium is involved in neurally mediated relaxation in corpus cavernosum, we determined electrical field stimulation (EFS) induced relaxation in both the presence and absence of endothelium, and we tested the effect of an inhibitor of NO synthase, NG-nitro-L-arginine (NOARG), in the absence of endothelium to examine if de-endothelialized tissue can still generate NO. Isolated corpus cavernosal strips from New Zealand White rabbits were used for isometric tension study using organ chambers. The endothelium was removed through denuding tissue. After the tissue was contracted with norepinephrine, EFS was performed at frequencies of 5, 15 and 40 Hz in the presence of guanethidine and atropine to evaluate NANC-selective nerural relaxation. The relaxation induced by EFS was observed after preincubation with NOARG(10(-4) M) for 30 minutes. L-arginine (10(-3) M) was then added for 30 minutes in the presence of NOARG before a second set of EFS studies were performed. Following norepinephrine precontraction, EFS relaxed corporal strips in both the intact and de-endothelialized strips. However, deendothelialization significantly impaired EFS induced relaxation (p < 0.05). NOARG attenuated relaxation induced by EFS and the addition of L-arginine reversed the inhibitory effect of NOARG in the strips with endothelium. In the strips without endothelium, NOARG still inhibited EFS induced relaxation. This relaxation was reversed by the addition of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Ureteroscopy offers an extension of endoscopic diagnosis and treatment to upper urinary tract malignancy. Combination of ureteroscopy and the Nd:YAG laser permits accurate and effective treatment of ureteral neoplasms. Nine highly selected patients, six males and three females, were treated with low grade papillary transitional cell carcinomas of the ureter with at least 24 months follow-up. Follow-up cytology and IVP have indicated no evidence for disease recurrence between the follow-up periods and minimal morbidity to the ureteroscopy and laser treatment.
Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the pharmacotherapy of erectile dysfunction. The purpose of this investigation was to determine whether the calcium channel blockers (CCB) relax cavernosal smooth muscle. Thirty-two rabbit cavernosal strips were contracted by electrical field stimulation, and contraction inhibition was tested in response to cumulative doses (10(-8) M. to 10(-4) M.) of verapamil (V), diltiazem (D), isradipine (I), nicardipine (Nc) and nifedipine (Nf). All of the calcium channel blockers were effective at inhibiting electrically induced contractions (p < 0.0001 when CCB was compared with control; p < 0.05 when V or D was compared with I, Nc or Nf). Sixteen cavernosal strips were precontracted with 10(-5) M. norepinephrine. Relaxation in response to cumulative doses of each CCB was determined. Verapamil and the dihydropyridines (isradipine, nicardipine and nifedipine), but not diltiazem, were effective at relaxing norepinephrine induced contractions at 10(-5) and 10(-4) M. with verapamil most effective at 10(-4) M. concentration (p < 0.0001 by ANOVA at both concentrations when V, I, Nc, or Nf was compared with control). Sixteen cavernosal strips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB followed by cumulative addition of norepinephrine (concentration range 10(-8) to 10(-4) M.). Preincubation with CCB did not affect the concentration of norepinephrine at which 50% of maximal cavernosal contractile response occurred (ED50). Maximum active tension of norepinephrine induced contractions was moderately decreased after CCB preincubation with 10(-4) M. of each dihydropyridine. It is concluded that the calcium channel blockers are effective in relaxing cavernosal smooth muscle and therefore possess potential as intracavernous pharmacotherapeutic agents for the treatment of erectile dysfunction. Verapamil appears to be the best candidate for further testing and clinical trial.
Vacuum constriction devices are generally considered to be a safe, effective, noninvasive means of producing erections in impotent men. However, long-term study of the effect of subatmospheric pressure on penile structures and vasculature has not been performed. We report the development of Peyronie's disease in a patient after 4 years of complication-free vacuum constriction device use.
Because of the rapid introduction and active marketing of newer antimicrobial agents for urinary tract infections, it is important to evaluate newer antibiotics critically. Critical evaluation should be based on published reports, spectrum of action, and, very importantly, cost. Newer agents should be compared with known effective agents on the basis of hospital antimicrobial sensitivity tests. Simple, uncomplicated urinary tract infections caused by community-acquired multiple drug-sensitive uropathogens can be treated with almost any currently available antimicrobial agent. In these situations, a low-morbidity, low-cost agent with limited dosage should be chosen. In general, a 3-day course of trimethoprim-sulfamethoxazole, nitrofurantoin, a first-generation cephalosporin, a penicillin agent, or in some cases a fluoroquinolone will be both medically and cost effective. For complicated urinary tract infections, more selectivity must be exercised in choosing an appropriate antibacterial agent. In these situations, it is necessary to initiate appropriate diagnostic studies to identify causes and to treat those complications appropriately. The choice of antibiotics must be based on culture results. Initial empiric treatment should be carried out with a broad-spectrum agent of low morbidity. In these complicated infections, fluoroquinolones may be effective with low expected morbidity.
To determine whether high-energy shock waves possess bactericidal potential, ATCC strains of Escherichia coli, Streptococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus were suspended in solution at concentrations approximating 10(6) bacteria per milliliter, placed in polypropylene cryovials, and immersed in the water bath of a Dornier HM3 lithotriptor. Each cryovial was then fluoroscopically guided to the epicenter of the f2 focal point and 2000 shocks at 20 kV applied. Suspensions were then serially diluted and colony counts obtained. The procedure was then repeated with 4000 shocks at 20 kV from the Dornier HM3 and 4000 shocks at intensity level 4 from a Wolff Piezolith 2200 shock wave lithotriptor. Comparison of shock-wave-treated and sham-treated bacterial suspensions revealed no significant difference in bacterial growth according to the colony count technique. We conclude that high-energy shock waves, whether generated by spark gap or piezoelectric array, do not possess significant bactericidal activity.
We report on 17 adult patients who underwent antegrade endoureteropyelotomy for primary (7) and secondary (10) ureteropelvic junction obstruction. Complications were limited to failure to relieve the obstruction, which occurred in 2 patients (12%) requiring a subsequent open pyeloplasty. The two failures were due to high insertion of the ureter in one, and lower renal pole vessel in the other case. A new endoureteropyelotomy stent was developed to enhance healing and patient comfort. No failures occurred due to technical difficulties.
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