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Despite the successes of Viagra, the quest for new and better therapy for erectile dysfunction (ED) continues. In a recent survey of the first 220 patients placed on Viagra at our institution, 101 (46%) quit taking the drug: 76% of those who quit were not satisfied with the results. Patients clearly want an efficacious, safe, convenient medication with rapid onset. To meet these consumer demands, numerous new therapies are being developed. These include new oral medications, new intracavernosal pharmacotherapies, new delivery systems (such as novel intracorporal injectors and transdermal agents) and combination therapies. What is known about these new medications and delivery systems will be presented. Hopefully, from these innovations will come therapies that will improve the overall success and acceptance of treatment for ED. Since it is unlikely that any single agent will ever provide a solution for all men with ED, an expanded armamentarium of treatment options will greatly enhance the chances that any given man will be able to find a therapy that is both acceptable and appropriate to him. International Journal of Impotence Research (2000) 12, Suppl 4, S158-S162.

The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.

The authors surveyed the current knowledge, opinions, and clinical practices of oncologists regarding pretherapy cryopreservation of semen from male cancer patients since the introduction of intracytoplasmic sperm injection (ICSI).A survey was sent to all members of the American Society of Clinical Oncology in Minnesota.Forty-six of 165 oncologists (28%) responded. Factors considered important in how strongly to recommend cryopreservation were patient age at the time of diagnosis (94%), type of treatment (83%), type of cancer (65%), urgency to initiate treatment (63%), and preexisting infertility (57%). Oncologists perceived patients to be significantly more concerned about cryopreservation than they were themselves during pretherapy counseling (P = 0.0005). Oncologists estimated that 27% of their patients chose to cryopreserve sperm. However, only 26% of the oncologists knew about ICSI. The cancers perceived to warrant cryopreservation the most were lymphomas, leukemias, and testicular carcinomas. The treatment modalities perceived to warrant cryopreservation the most were distributed among various chemotherapy and radiation regimens. A majority of respondents to the survey knew where patients could go to cryopreserve sperm (89%), but less than half of the respondents gave accurate information about the cost.Most of the oncologists surveyed were unaware of recent advances in reproductive technology in which only a few sperm are needed for successful in vitro fertilization with ICSI. This lack of awareness may be contributing to underutilization of sperm cryopreservation by male cancer patients. Currently, all male cancer patients of reproductive age who will have treatment that may affect testicular function and who may desire children in the future should cryopreserve sperm before the initiation of therapy.

Human prostatic secretion and seminal plasma contain certain protein kinase activities. Protein kinases play important roles in regulating a vast variety of cellular functions. The objective of this study was to determine whether one of these protein kinase activities in human prostatic secretion and seminal plasma is due to CK2, a messenger-independent, serine/threonine protein kinase that has considerable potential as a regulatory enzyme. By employing an anti-CK2 antibody and a CK2-specific peptide substrate, we have established that CK2 is present in these secretions. Approximately 70% of the CK2 activity present in seminal plasma of normozoospermic men (n = 49) is correlated to the number of sperm originally present in the semen. Further, both the prostate gland and the seminal vesicles are sources of CK2 activity in the seminal plasma of vasectomized men (n = 38). Although there was considerable variation between individuals in CK2 activity, the variation in repeat semen samples of the same vasectomized men (n = 6) was within 21%. There was no correlation of CK2 activity in seminal plasma with age for vasectomized (27-48 years, n = 38), oligozoospermic (28-43 years, n = 24), or normozoospermic men (26-48 years, n = 49). These data suggest that the majority of CK2 activity in the seminal plasma of normozoospermic men originates from sperm but that the prostate and seminal vesicles are accessory sex-gland sources of this enzyme.

A number of peptidases which can metabolize certain bioactive peptides and growth factors have been identified in seminal plasma. Our goal in this study was to determine molecular properties and the tissue source(s) for one of these peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma.We measured the activities of DPP IV with the dipeptide glycylprolyl-p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of men who were vasectomized or with different sperm concentrations, and in prostatic and seminal vesicle secretions of men undergoing prostatic surgery.DPP IV in seminal plasma of vasectomized men was a membrane associated dimer comprised of subunits of approximately 110 kDa. Its activity did not differ in seminal plasmas of vasectomized, azoospermic, oligozoospermic and normozoospermic men indicating no correlation with the concentration of sperm originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity were present in prostatic secretion, but absent from that of the seminal vesicles. These data indicate that the prostate gland is the primary source of DPP IV activity in seminal plasma. There was little variation in its activities in repeat seminal plasma samples from the same individual, and there was no change in its activity with age to 50 years.DPP IV in seminal plasma was derived from the prostate gland and it may be useful as a bioindicator of prostate function and/or disease with age in men.

The effects of exogenous growth hormone (GH) and FSH on development of the testes in intact prepubertal boars was investigated. Twenty-four boars received one of four daily treatments from 8 through 40 days of age: 1) 90 micrograms porcine (p) GH/kg body weight (BW), 2) 100 micrograms pFSH/kg BW, 3) GH + FSH, or 4) vehicle only (control). Plasma testosterone levels, measured at 10-day intervals, were similar among groups of boars throughout the study. Body weights among groups were similar during treatment, and testicular weight between treatment groups did not differ at castration (100 days of age). However, total length of the seminiferous tubule per testis in FSH-treated boars was 59% greater than in GH-treated animals (2705 vs. 1704 m; p0.05). Diameter of the tubule in GH-treated boars was 58% greater than in FSH-treated boars (p = 0.03). Relative mass of spermatocytes and spermatids in GH-treated animals exceeded that in controls by 2.5-fold and that in FSH boars by 75-fold (p = 0.05). There were no differences in effects of GH + FSH treatment as compared to control treatment; none of the treatments affected any interstitial tissue parameter measured. These results suggest that exogenous FSH had a mitogenic effect on Sertoli cells while delaying tubular maturity, whereas exogenous GH promoted tubular and Sertoli cell maturation, defined as increased Sertoli cell size, lumen formation, and onset of spermatogenesis.

We report a case of severe erosion and cellulitis at the base of the penis as a result of vacuum suction device constriction bands left on for 4 hours in a spinal cord injured patient with paraplegia and hypesthesia of the genital area. All patients using vacuum suction devices need to be properly educated regarding usage and risks with adequate follow up; patients with hypesthesias and spinal cord injuries need information specifically related to their decreased or absent level of sensation. Only two out of seven vacuum suction device brochures reviewed warn of the risk to patients with decreased sensation in the penis, but none specifically address usage or risks to men with spinal cord injuries.

Therapeutic options for patients with bilateral renal cancer or cancer in a solitary kidney are limited to partial nephrectomy or bilateral radical nephrectomy with subsequent renal transplantation or dialysis. The outcome after partial nephrectomy is well documented, but few reports discuss the long-term survival of patients receiving chronic dialysis or after renal transplantation. Information regarding the long-term prognosis for these patients is important when deciding on the appropriate treatment.The authors retrospectively evaluated the long-term prognosis of 23 patients who lost renal function because of surgery for renal cell carcinoma or Wilms' tumor between 1970 and 1990.Twelve patients had renal transplantation (Tx group), and 11 had chronic dialysis (DS group). In the Tx group, four patients had Wilms' tumor and eight had renal cell carcinoma (Stage I, 5 patients; Stage II, 2 patients; Stage III, 1 patient). In the DS group, three patients had Wilms' tumor, and eight had renal cell carcinoma (Stage I, 5 patients; Stage III, 2 patients; Stage IV, 1 patient). Unexpectedly, 9 of 11 (82%) patients from the DS group died of cancer, compared with 1 of 12 (8%) patients who had transplantation (P = 0.0133) despite comparable stages of renal cell carcinoma and Wilms' tumor in the two groups.For patients who have had bilateral nephrectomy or removal of a solitary kidney, the authors recommend waiting at least 12 months, during which time the patient receives dialysis, before proceeding with transplantation if there is no evidence of recurrent tumor.

Isolated renal cortical collecting tubules obtained from rabbits treated chronically with desoxycorticosterone acetate (DOCA) have been found to possess elevated transepithelial potential differences and a greatly increased capacity for ion transport. Structural exmination of tubules from rabbits exposed to either DOCA or dexamethasone for 11--18 d reveals a marked increase in basolateral cell membrane area in these tubules. Morphometric analysis shows that this effect is specifically on the basolateral membrane area of only one of the two cell types found in this nephron segment. Increases of greater than 140% and 90% are found for the basolateral membrane area of the principal cells for DOCA and dexamethasone, respectively, but no change could be detected in the basolateral membrane area of the intercalated cells found in this nephron segment. No siginificant changes were found in luminal membrane area, cell number, or cell volume for either cell type. These observations demonstrate that significant changes in membrane area can occur in differentiated epithelia and suggest that this may be an important mechanism for modulating epithelial transport capacity.

Approximately one third of infertile men present with varicocele, while the incidence among males in the general public is approximately 15 per cent. The etiology may be a longer left spermatic vein with its right-angle insertion into the left renal vein and/or absence of valves, which causes a higher hydrostatic pressure in the left spermatic vein causing dilatation. The nutcracker phenomenon is also a possible etiology. Much of the pathophysiology is still unknown, but increased blood flow causing an elevated intratesticular temperature may be of significance. Though there are many recent reports on the importance of a subclinical varicocele, we are not convinced of its significance. The best method for diagnosis remains a good clinical examination. The incidence of adolescents with varicocele is about the same as men with varicocele (approximately 15 per cent). Adolescents with varicocele should be treated if the testicular mass is decreased or if they are symptomatic. Surgical ligation is still the preferred method of treatment. Percutaneous treatment of varicoceles has an approximately 11 per cent incidence of minor complications and an occlusion rate of 73 per cent with a recurrence rate of 5 per cent. We reserve percutaneous treatment for recurrent varicoceles after surgical ligation, but primary percutaneous therapy is a reasonable approach.