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H Lepor

Publications and source records attributed to H Lepor.

174 records · Page 10Linked to original sources
PubMed1984

Characterization of muscarinic cholinergic receptor binding in the vas deferens, bladder, prostate and penis of the rabbit.

Radioligand receptor binding techniques were used to characterize the muscarinic cholinergic receptor in the vas deferens, bladder, prostate and penis of the rabbit. This study represents the first comparative investigation of a neurotransmitter receptor in the genitourinary tract using radioligand receptor binding methods. A single high affinity muscarinic binding site was identified in the vas deferens (Kd = 0.16 nM), bladder (Kd = 0.15 nM) and prostate (Kd = 0.17 nM), using [3H]N-methylscopolamine ([3H]NMS), a muscarinic antagonist. Two high affinity [3H]NMS binding sites (Kd1 = 0.08 nM; Kd2 = 1.39 nM) were found in the penis. The pharmacology of the NMS binding sites in the vas deferens, bladder and prostate was characterized by competitive binding experiments with [3H]NMS and several unlabelled muscarinic and nonmuscarinic drugs. Noncholinergic drugs, as expected, were weak inhibitors of [3H]NMS binding. The values of the IC50's for the muscarinic drugs atropine, pirenzepine and oxotremorine in the genitourinary tissues of the rabbit were similar to values reported in nongenitourinary tissues demonstrating homogeneity of muscarinic receptors. The mean Hill coefficients for the muscarinic antagonist (atropine 0.81 to 0.878) were significantly different than for the muscarinic agonist (oxotremorine 0.39 to 0.44) in all genitourinary tissues, a binding property of muscarinic receptors identified in other tissues. The requirements for the characterization of cholinergic muscarinic receptors have been fulfilled for several genitourinary tissues of the rabbit. Radioligand receptor binding methods can now be applied to investigating the relationship between genitourinary dysfunction and alterations in the muscarinic cholinergic receptors.

Animals↗
PubMed1984

Characterization and localization of the muscarinic cholinergic receptor in human prostatic tissue.

Radioligand receptor binding and autoradiography were used to characterize and localize the muscarinic cholinergic receptor in human benign prostatic hyperplastic tissue. These methods have not been used previously to investigate the autonomic innervation of the human prostate. The binding of [3H]N-methylscopolamine ([3H]NMS), a muscarinic cholinergic antagonist, to homogenates of human prostate was saturable and of high affinity. The equilibrium dissociation constant, (Kd), for [3H]NMS binding to human prostate homogenates was 0.10 +/- 0.03 nM (mean +/- SEM). The values of the Kd's for [3H]NMS binding to prostates of man (0.10 nM), dog (0.20 nM), pig (0.11 nM), rat (0.07 nM) and rabbit (0.15 nM) were similar, suggesting homogeneity of muscarinic cholinergic receptors in varying species. The mean density, B(max), of muscarinic cholinergic receptors identified in the human prostate was 2.1 fmol./mg. prostate wet weight. The relative density of receptors in the human prostates were similar in the homogenates and slide-mounted tissue sections. The pharmacology of NMS binding sites on slide-mounted tissue sections was evaluated by competitive binding experiments using [3H]NMS and atropine. The IC50 corrected of atropine on slide-mounted tissue sections (0.42 nM) was similar to values obtained in prostate homogenates (1.16 nM). Autoradiography on slide-mounted tissue sections demonstrated that the muscarinic cholinergic receptors were localized to the epithelium of the prostate. The ratio of specific NMS binding in the epithelial and stromal components of the prostate, expressed as autoradiographic grains/unit area and autoradiographic grains/cell, was 71:1 and 33:1 respectively. Because prostatic secretion is dramatically enhanced by muscarinic cholinergic agonists, localization of muscarinic cholinergic receptors to the epithelium is consistent with the neuropharmacology of prostatic secretion. These studies have provided basic insight into the neuropharmacology of the prostate. Future studies will be necessary to characterize and localize other neurotransmitters in the human prostate in order to further enhance our understanding of prostatic function.

Animals↗
PubMed1984

Characterization of alpha1 adrenergic receptors in human benign prostatic hyperplasia.

Bladder outlet obstruction in men with benign prostatic hyperplasia is decreased following administration of prazosin, a selective alpha1 adrenergic antagonist. Prazosin presumably binds and antagonizes alpha1 adrenergic receptors on the smooth muscle cells of the prostatic adenoma. This study represents the first identification and characterization of alpha1 adrenergic receptors in the prostate using radioligand receptor binding methods. The binding of [3H] prazosin in homogenates obtained from human prostatic adenomas was saturable and a single high affinity prazosin binding site was identified (Kd = 0.29 +/- 0.09 nM). The alpha1 adrenergic receptor concentration in these homogenates ranged between 0.28 to 2.05 fmol./ mg. wet wt. prostate. The equilibrium dissociation constant and density of prazosin binding sites were similar in different regions of an enucleated prostate suggesting homogeneity of receptor density and receptor binding sites within an adenoma. The receptor density was not directly proportional to the weight of the surgically removed adenoma. The pharmacology of the prazosin binding sites was characterized by competitive binding experiments using [3H] prazosin and several unlabelled adrenergic analogs. The IC50's determined from competitive binding experiments using [3H] prazosin and alpha-methylnorepinephrine, rauwolscine and corynanthine were characteristic of alpha1 adrenergic receptor binding.

Binding Sites↗
PubMed1984

Urethral reconstruction in boys with classical bladder exstrophy.

A total of 24 boys with classical bladder exstrophy underwent initial urethral reconstruction at our hospital between 1975 and 1982. Penile reconstruction in male patients with classical bladder exstrophy includes penile lengthening, release of the dorsal chordee and reconstruction of the urethra. The former 2 procedures are performed during the primary bladder closure and urethroplasty usually follows bladder neck reconstruction. A modified Young urethroplasty was done in 22 of the 24 patients. Preputial pedicle grafts of free full thickness skin grafts were used for urethroplasty in 2 boys with insufficient penile skin. Fistulas requiring surgical revision developed after urethroplasty in 21 per cent of the patients. A prior osteotomy was associated with a decreased fistula rate. The cosmetic and preliminary functional results of the penile reconstruction were assessed by parental interviews. The definitive assessment of the penile reconstruction will be determined when these boys reach sexual maturity.

Bladder Exstrophy↗
PubMed1984

Decreased prostatic secretory function in canine benign prostatic hyperplasia is not due to decreased levels of muscarinic cholinergic receptors.

The ejaculatory volume and the prostatic secretory capacity (ml. ejaculate per gm. prostate wet weight) were determined for a group of dogs with normal and hyperplastic prostates. The ejaculatory volume and prostatic secretory capacity in dogs with BPH were decreased by 70 per cent and 80 per cent respectively, compared to dogs with normal prostates. Radioligand receptor binding using [3H]N-methylscopolamine, a muscarinic cholinergic antagonist, was performed on a similar group of dogs with normal and hyperplastic prostates. The mean equilibrium dissociation constant for the binding of [3H]N-methylscopolamine to homogenates obtained from normal and hyperplastic prostates was 0.21 nM. and 0.19 nM. respectively, demonstrating that the affinity of the receptor binding sites was not altered by the development of BPH. The tissue density of the muscarinic cholinergic receptors (fmol. per mg. prostate wet weight) and the cellular density of these receptors (fmol. per mg. DNA) were not significantly different in normal and hyperplastic prostates. These data indicate that the dramatic reduction in prostatic secretory capacity associated with canine BPH is not related to changes in the muscarinic cholinergic receptor binding capacity.

Animals↗
PubMed1983

Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations.

The technique for radical retropubic prostatectomy has been modified to avoid injury to the branches of the pelvic plexus that innervate the corpora cavernosa. The surgical procedure is based on an understanding of the anatomical relationships between the branches of the pelvic plexus that innervate the corpora cavernosa, the capsular branches of the prostatic vessels that provide the scaffolding for these nerves, and the lateral pelvic fascia. The modifications involve two steps in the procedure: 1) the incision in the lateral pelvic fascia is placed anterior to the neurovascular bundle, which is located dorsolateral to the prostate along the pelvic sidewall; 2) the lateral pedicle is divided close to the prostate to avoid injury to the branches of the pelvic plexus that accompany the capsular vessels of the prostate. Pathologic evaluation of 16 prostatic specimens removed by this modified procedure demonstrated no compromise in the adequacy of the surgical margins. Postoperative sexual function was evaluated in 12 men who underwent the procedure 2-10 months previously. All have experienced erections and six have achieved successful vaginal penetration and orgasm. Of the six patients with sexual partners who have been followed 6 months or longer, five (83%) are fully potent. These data indicate that it is possible to cure localized prostatic cancer with surgery and maintain postoperative sexual function.

Adenocarcinoma↗
PubMed1983

Primary bladder closure and bladder neck reconstruction in classical bladder exstrophy.

The surgical results of 28 consecutive initial bladder closures and 25 consecutive initial bladder neck reconstructions performed for classical bladder exstrophy at our hospital between 1975 and 1982 are presented. Partial bladder prolapse occurred in 2 cases and complete wound dehiscence never occurred following the initial primary bladder closure. Urinary continence following bladder neck reconstruction was assessed from parental interviews. An excellent surgical result was defined either as achievement of a daytime dry interval for more than 3 hours or less than 1 incontinent episode per day. According to these parameters, an excellent surgical result was achieved in 86 and 80 per cent of children, respectively. In 21 children evaluated with excretory urograms between 1/2 and 6 years after bladder neck reconstruction 10 per cent of the renal units showed significant hydronephrosis and deterioration of function. The 2 patients who had upper tract deterioration were not followed postoperatively at our institution and the diagnosis of bladder outlet obstruction was delayed when excretory urograms were not obtained during the first postoperative year. This review of the surgical results following primary bladder closure and bladder neck reconstruction for classical bladder exstrophy demonstrates that secure abdominal wall closure and urinary continence can be achieved with minimal morbidity and with infrequent deterioration of renal function following staged functional bladder closure.

Bladder Exstrophy↗
PubMed1982

The influence of hormonal therapy on survival of men with advanced prostatic cancer.

Although hormonal therapy has been used for almost 40 years in the management of patients with prostatic cancer there is no consensus on whether this treatment prolongs life in these men. In an attempt to answer this question survival of 65 control patients seen from 1937 to 1940 was compared to survival of patients who received hormonal therapy from 1942 to 1944. These intervals were selected in an attempt to minimize the influence of medical advances other than hormonal therapy. Although life table graphs indicated that survival was extended for patients who entered in the hormonal era our analyses indicate that the difference in survival between treatment and control groups can be accounted for by a trend toward lower mortality in patients who entered later in the study rather than by hormonal therapy. The temporal trend was noted in all major subgroups of patients. These data suggest that in this study hormonal therapy had little impact on the over-all survival of men with advanced prostatic cancer and that every effort must be made to explore new avenues for the treatment of these patients. In the future, hormonal therapy may be most effectively used when the poorly responsive patients can be identified at an earlier time in the disease and treated with alternate forms of therapy.

Adenocarcinoma↗
PubMed1981

Nephrogenic adenoma: clinical features and therapeutic considerations.

Nephrogenic adenoma is a benign metaplastic lesion that usually responds to endoscopic treatment. Although occasionally it has been present simultaneously with another malignancy there has been no evidence that a nephrogenic adenoma has ever transformed into a carcinoma. The symptoms of a nephrogenic adenoma can be severe but these lesions can be treated with transurethral surgery. The lesions can occur throughout the bladder and in the urethra. They usually are associated with trauma to the urothelium. Postoperative followup is needed because these lesions tend to have a symptomatic recurrence. An increased awareness of nephrogenic adenoma by urologists and pathologists may lead to its more frequent diagnosis.

Adenoma↗
PubMedDate not supplied

The emerging role of alpha antagonists in the therapy of benign prostatic hyperplasia.

The rationale for using alpha blockade to treat benign prostatic hyperplasia (BPH) is based on the physiology and pharmacology of prostate smooth muscle. Approximately 20% of the area density of the prostate adenoma is smooth muscle. In vitro isometric tension studies have demonstrated that the contractile properties of the human prostate adenoma are mediated primarily by alpha 1 adrenoceptors. Alpha blockers presumably decrease the resistance along the prostatic urethra by relaxing the smooth muscle component of the prostate. Over the past 14 years, at least 16 clinical trials have confirmed the efficacy of alpha blockade in the treatment of BPH. The primary advantage of terazosin over all other commercially available alpha blockers is that its longer half-life allows for a once-daily dosage regimen. Two Phase II studies conducted in the United States, a multicenter dose titration randomized withdrawal study and the author's personal experience with terazosin, are summarized in this report. Overall, the peak urinary flow rate increased 50% and the mean urinary flow rate increased 46% following terazosin therapy. The mean obstructive and irritative scores improved 67% and 35%, respectively. The adverse reactions occurring with an incidence greater than 5% included headache (10%), asthenia (7%), and dizziness (14%). All adverse events were reversible on termination of therapy. The preliminary experiences with alpha blockers for the treatment of BPH has been very encouraging. Yet, the definitive role of alpha blockade in BPH awaits the reporting of multicenter, randomized placebo-controlled studies.

Adrenergic alpha-Antagonists↗