In vitro assessment of the efficacy of thermal therapy in human benign prostatic hyperplasia.

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.

Delayed timing of intrauterine insemination results in a significantly improved pregnancy rate in female partners of quadriplegic men.

OBJECTIVE: To review pregnancy rates obtained with three protocols used during development of a successful therapy for infertility in couples in which the male partner had spinal cord injury. DESIGN: Retrospective chart review. SETTING: Private infertility center. PATIENT(S): Eleven quadriplegic men and their spouses undergoing intrauterine insemination. INTERVENTION(S): Protocol 1: Intrauterine insemination was performed 24 hours after the LH surge was detected in unstimulated cycles. Sperm were prepared by standard sperm washing. Protocol 2: Female partners were stimulated with clomiphene citrate and hCG. Sperm were inseminated 32-34 hours after hCG injection. Sperm preparation was by serum swim-up or density gradient preparation. Protocol 3: Identical to protocol 2, except the insemination was delayed to 38-40 hours after hCG injection. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Five patients were enrolled into protocol 1 and underwent a total of 19 inseminations with no subsequent pregnancies. They then underwent protocol 2, but no pregnancies resulted from inseminations. Four of the original couples, along with six additional couples, underwent insemination in protocol 3. A total of 19 inseminations were performed, and 6 of the 10 patients (60%) became pregnant. The success of insemination at 38-40 hours after hCG administration was significantly better than that of the initial two protocols (P<.05). No differences were observed in sperm quality between protocol 2 and protocol 3. Overall, 73% (8 of 11) of the patients became pregnant. CONCLUSION(S): Intrauterine insemination 38-40 hours after the hCG injection results in an improved chance of pregnancy. These results indicate that many couples with spinal cord injury-associated male infertility can be treated with intrauterine insemination of sperm treated by serum swim-up, with a high probability of success.

Premature ejaculation: a psychophysiological approach for assessment and management.

This article distinguishes several subtypes of biogenic and psychogenic premature ejaculation (PE) according to their etiologic features: the physiological PE types of (a) neurologic constitution, (b) acute physical illness, (c) physical injury, and (d) pharmacologic side effect; and the psychological PE types of (a) psychological constitution, (b) acute psychological distress, (c) relationship distress, and (d) psychosexual skills deficit. Attention is given to assessment and differential diagnosis, and to specific treatment of the types of PE, such as the pharmacologic management of difficult neurologic cases. Effective psychosexual treatment combines multiple strategies such as physiological relaxation, pubococcygeal muscle training, cognitive and behavioral pacing strategies, and the involvement of the partner in the therapy. Treatment should determine the specific type of PE and comprehensively address its particular features in order to improve long-term treatment effectiveness.

New therapies and delivery mechanisms for treatment of erectile dysfunction.

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.

Critical windows of exposure for children's health: the reproductive system in animals and humans.

Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.

The effect of extracellular ice and cryoprotective agents on the water permeability parameters of human sperm plasma membrane during freezing.

A firm biophysical basis for the cryopreservation of human spermatozoa is limited by a lack of knowledge regarding the water permeability characteristics during freezing in the presence of extracellular ice and cryoprotective agents (CPA). Cryomicroscopy cannot be used to measure dehydration during freezing in human spermatozoa because of their highly non-spherical shape and their small dimensions which are at the limits of light microscopic resolution. Using a new shape-independent differential scanning calorimeter (DSC) technique, volumetric shrinkage during freezing of human sperm cell suspensions was obtained at cooling rates of 5 and 10 degrees C/min in the presence of extracellular ice and CPA. Using previously published data, the human sperm cell was modelled as a cylinder of length 40.2 micrometer and a radius of 0.42 micrometer with an osmotically inactive cell volume, V(b), of 0.23V(o), where V(o) is the isotonic cell volume. By fitting a model of water transport to the experimentally obtained volumetric shrinkage data, the best fit membrane permeability parameters (L(pg) and E(Lp)) were determined. The 'combined best fit' membrane permeability parameters at 5 and 10 degrees C/min for human sperm cells in modified media are: L(pg) = 2. 4x10(-14) m(3)/Ns (0.14 micrometer/min-atm) and E(Lp) = 357.7 kJ/mol (85. 5 kcal/mol) (R(2) = 0.98), and in CPA media (with 6% glycerol and 10% egg yolk) are L(pg)[cpa] = 0.67x10(-14) m(3)/Ns (0.04 micrometer/min-atm) and E(Lp)[cpa] = 138.9 kJ/mol (33.2 kcal/mol) (R(2) = 0.98). These parameters are significantly different from previously published parameters for human spermatozoa obtained at suprazero temperatures and at subzero temperatures in the absence of extracellular ice. The parameters obtained in this study also suggest that damaging intracellular ice formation (IIF) could occur in human sperm cells at cooling rates as low as 25-45 degrees C/min, depending on the concentrations of the CPA. This may help to explain the discrepancy between the empirically determined optimal cryopreservation cooling rates (<100 degrees C/min) and the numerically predicted optimal cooling rates (>7000 degrees C/min) obtained using previously published suprazero human sperm permeability parameters which do not account for the presence of extracellular ice.

A survey of oncologists regarding sperm cryopreservation and assisted reproductive techniques for male cancer patients.

BACKGROUND: 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). METHODS: A survey was sent to all members of the American Society of Clinical Oncology in Minnesota. RESULTS: 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. CONCLUSIONS: 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.

Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human epididymis.

OBJECTIVE: To determine the regional distribution and relative expression of 5alpha-reductase type 1 and type 2 mRNA within the human testis and regions of the epididymis. DESIGN: Prospective observational study. SETTING: University academic medical center. PATIENT(S): Two young adult male organ donors. INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The distribution of 5alpha-reductase type 1 and type 2 mRNA in the testis and regions of the epididymis was detected by Northern blot analysis. The relative abundance of each 5alpha-reductase mRNA was evaluated using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in which cyclophilin mRNA, a house-keeping gene product, was coamplified as the reference standard. RESULT(S): Northern blot analysis revealed the 5alpha-reductase type 2 transcript in the midcaput, distal caput, corpus, and proximal cauda of the epididymis, but the transcript was undetectable in the testis, proximal caput, and distal cauda region. No transcript for the type 1 isozyme was detected by Northern blot. The more sensitive RT-PCR showed low levels of type 1 mRNA in the testis and epididymis, with the highest abundance in the proximal caput. Type 2 mRNA of 5alpha-reductase was most abundant in the midcaput, was decreased in the more distal regions, and was more abundant than type 1 mRNA in all epididymal regions except for the proximal caput. CONCLUSION(S): Both 5alpha-reductase type 1 and type 2 mRNAs are present in the human epididymis. The type 2 isozyme mRNA is predominant, being more highly expressed than the low-abundance type 1 mRNA.

Protein kinase CK2 activities in human prostatic and seminal-vesicle secretions and seminal plasma.

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.

Analysis of fibronectin on human sperm.

PURPOSE: The purpose of this study was to localize fibronectin on human sperm and correlate its distribution with the morphological and functional integrity of sperm. MATERIALS AND METHODS: Semen samples were collected and sperm fractionated by swim-up. Subsets of the swim-up sperm were capacitated and acrosome reacted. Damage to swim-up sperm was induced by freezing and thawing. The presence of fibronectin on the surface of sperm was determined by immunocytochemistry. RESULTS: FN immunoreactivity was variable but staining on the sperm tail was consistently highest, whereas FN immunoreactivity over the acrosome and equatorial band was consistently lowest. Capacitation and acrosome reaction did not substantially change the distribution of FN staining. However, swim-up sperm had significantly less FN immunoreactivity (4%) than sperm that were unable to swim-up (12%; p < 0.01). Sperm that were deliberately damaged by freeze/thaw showed significantly increased FN binding (p < 0.01). FN immunoreactivity was inversely correlated with sperm viability (r = -0.68), motility (r = -0.70), and morphology (r = -0.63). CONCLUSIONS: This study demonstrates that only a minority of the sperm in an ejaculate stain positive for FN and the localization of FN in positive sperm is primarily to the tail. Inferior sperm stain more frequently for FN leading to an inverse correlation between FN staining and sperm quality. Taken together, these results do not support a role for FN in sperm-egg binding. However, FN staining may provide a method for selecting the highest quality sperm for use in assisted reproduction techniques.

A surface swab method for culturing Foley catheters assays the pericatheter (urethral) but not the urine (luminal) microbial population.

Assessment of the urethral flora in patients with indwelling bladder catheters is problematic in the presence of urinary tract infection (UTI). A new surface swab method that samples the external catheter surface without interference from contaminated luminal contents is described. In vitro, recovery of adherent bacteria from the external catheter surface by the surface swab method was proportional to the bacterial density as measured by a comparison scrape method. In a prospective longitudinal assessment of three chronically catheterized subjects with polymicrobial catheter-associated UTI, a conventional roll plate catheter culture method suggested substantial overlap between the urethral and urine microbial populations, possibly a result of contamination of catheter cultures by infected urine. In contrast, the surface swab method revealed little overlap between these floras, evidence suggesting a predominantly luminal (rather than meatal) route of UTI acquisition. The new surface swab method should prove useful in future studies of the pathogenesis and prevention of catheter-associated UTI.

Long-term follow-up of patients receiving injection therapy for erectile dysfunction.

OBJECTIVES: During the last decade, vasoactive intracavernosal pharmacotherapy (VIP) has been used extensively for the treatment of erectile dysfunction. However, there is concern about high discontinuation rates and the possibility of long-term complications. Because of few long-term studies on VIP, we investigated efficacy, side effects, satisfaction index, and drop-out rate for injection therapy in patients who started treatment more than 5 years ago. METHODS: Questionnaires were mailed to 108 patients who were started on VIP more than 5 years ago, between November 1984 and July 1989. The hospital records and data from the 100 responders (93%) were reviewed. RESULTS: Only 32% of the patients continue to use VIP. Most (56%) of those who discontinued did so during the first year. The patients cited one or more of the following reasons for discontinuation: desire for a permanent modality of therapy (29%), lack of a suitable partner (26%), fear of needles (23%), poor response (23%), fear of complications (22%), and lack of sexual spontaneity (21%). This study, which has one of the longest follow-up periods in the literature, has significant new findings in three areas: discontinuation rates fall after 2 years, long-term complications are relatively minor, and patients who discontinue therapy are significantly older or have a poor initial impression of VIP. Paradoxically, discontinuing VIP was apparently unrelated to side effects or etiology of erectile dysfunction, and 82% of patients would still recommend VIP to a friend. CONCLUSIONS: This study conclusively shows that because of high initial satisfaction and relatively minor side effects, VIP should remain as one of the initial options for long-term treatment of erectile dysfunction. However, despite seemingly doing well, patients often discontinue therapy, and therefore should be followed closely so that alternative therapy can be offered.

Premature ejaculation: a psychophysiological review.

This review examines the most common male sexual dysfunction, premature ejaculation (PE). The prevalence, classification, neurophysiology, neuropharmacology, and psychological studies that offer evidence useful for understanding and clinically evaluating PE are reviewed. It is proposed that there are two basic kinds of PE: biogenic and psychogenic. Studies reporting pharmacological aspects of ejaculation offer some suggestions regarding the mechanisms of ejaculation as well as possible pharmacologic aid for some premature ejaculators. The traditional assumption among sex therapists that PE is almost universally caused by psychological features, and easily treated with sex therapy behavioral techniques, is drawn into question. Based on the limited available results from systematic investigations, behavioral treatments for PE remain beneficial to only a minority of men three years after treatment ends, suggesting that this male dysfunction is difficult to treat effectively. The mediocre results reported in treatment outcome studies may be due, in part, to reports on heterogeneous groups of premature ejaculators, for whom treatment has been generalized rather than targeted to the specific type of PE. We propose a biological and psychological etiology. With more discriminating assessment and more specific diagnosis of PE, and with treatment designed to address the particular type of PE, long-term outcome should improve for this common sexual dysfunction.

Male menopause. How to define it, how to treat it.

There has been a recent explosion of articles in the medical literature and newsbites on television and in the lay press regarding male menopause. Yet, many men are not familiar with the changes in sexuality that accompany aging. Primary care physicians therefore need to be well informed about the concept of male menopause and the dos, don'ts, and unknowns of treating it with testosterone.

Microdeletions in the Y chromosome of infertile men.

BACKGROUND: Some infertile men with azoospermia or severe oligospermia have small deletions in regions of the Y chromosome. However, the frequency of such microdeletions among men with infertility in general is unknown. We sought to determine the prevalence of Y-chromosome microdeletions among infertile men and to correlate the clinical presentation of the men with specific deletions. METHODS: We studied 200 consecutive infertile men. Each man was evaluated comprehensively for known causes of infertility, and Y-chromosome microdeletions were studied with use of the polymerase chain reaction to amplify specific regions of the chromosome. The Y chromosomes of 200 normal men were also analyzed. RESULTS: Fourteen infertile men (7 percent) and four normal men (2 percent) had microdeletions of the Y chromosome. Nine of the infertile men had azoospermia or severe oligospermia (sperm concentration, <5 million per milliliter), four had oligospermia (sperm concentration, 5 million to <20 million per milliliter), and one had normospermia (sperm concentration, > or = 20 million per milliliter). The size and location of the deletions varied and did not correlate with the severity of spermatogenic failure. The fathers of six infertile men with microdeletions were studied; two had the same deletions as their sons, and four had no deletions. CONCLUSIONS: A small proportion of men with infertility have Y-chromosome microdeletions, but the size and position of the deletions correlate poorly with the severity of spermatogenic failure, and a deletion does not preclude the presence of viable sperm and possible conception.