The multilayered structure of the human corpus spongiosum.

PURPOSE: Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In the case of shortage of tissue, engineered tissue may enhance urethral reconstruction. As the corpus spongiosum (CS) is important in supporting the function of the urethra, tissue engineering of the urethra should be combined with reconstruction of a CS. For that purpose, detailed knowledge of the composition of the CS, more specifically its extracellular matrix (ECM) and vascularization is needed for scaffold design. The objective of this study is to analyze the microarchitecture of the CS through (immuno) histology and scanning electron microscopy (SEM). METHODS: The CS including the urethra of patients undergoing male-to-female genital confirming surgery was harvested. This CS was fixed and processed for either (immuno) histology or for SEM. RESULTS: Four layers could be distinguished in the CS; first a transition zone from urethra epithelium to a collagen rich layer, which was highly vascularized, followed by a second, elastin rich layer. The third layer was formed by veins, arteries and vascular spaces and the last layer showed the transition from this vascular rich region to the collagen rich tunica albuginea. In this layer collagen bundles intertwined with elastic fibres. In the CS different components of the ECM were visible and distinguishable. CONCLUSION: This study provides novel and detailed information on the microarchitecture of the CS and the distribution of vascularization, which is important for scaffold design in tissue engineering.

[Hormonal contraception in men]. / Hormonale anticonceptie bij de man.

Over the past few decades, female hormonal contraception has been seen to be very successful. However, this has still not resulted in a hormonal contraceptive for men. Certain injectable combinations ofandrogens and progestagens have been found to suppress spermatogenesis. All combinations that have been tested so far suffer from a relative lack of efficacy, a long lag time to achieve azoospermia, requiring the user to undergo one or more semen analyses, a moderate user friendliness, and concerns about the long-term safety and reversibility. It is not to be expected that male hormonal contraception will become a serious alternative to the already existing female equivalent during the coming 5 years.

Cardiovascular risk among men seeking help for erectile dysfunction.

PURPOSE: The introduction of sildenafil put the risk of cardiovascular disease (CVD) among men with erectile dysfunction (ED) on the agenda of physicians. The question arose, Is EDsentinel to CVD? We sought to answer this question in the present study. METHODS: A historical cohort study was set up using medical records of general practices all over the Netherlands. Incident cases of ED were selected before and after the introduction of sildenafil using a catchment population of 60,000 men aged 35 to 74 years. Two to three men without ED (controls) were, subsequently, matched to each case. Incidence of CVD was determined for cases and controls, respectively. RESULTS: Overall, incidence of ED doubled from 5.3 per 1000 men-years in the period before introduction of sildenafil to 10.1 after the introduction. The relative risk of incident CVD among men with ED compared to controls was 1.7 [95%-CI 0.9-3.3] before the introduction and 1.1 [95%-CI 0.6-1.8] afterwards. CONCLUSIONS: While ED could be seen as a marker for CVD before the introduction of sildenafil, it was clearly not afterwards.

[Vasectomy: indications and implementation in historic perspective]. / Vasectomie: indicaties en uitvoering in een historisch perspectief.

Approximately 35,000 vasectomies were performed in the Netherlands in 2004. Although vasectomy may be looked upon as the most reliable method of contraception (risk of pregnancy in the first year: 0.08-0.15%), realistic preoperative counselling about possible complications such as haemorrhage (5%), wound infection (5%), and haematoma (14%) and long-term consequences such as the wish for renewed fertility (2.6% of the men opt for vasectomy reversal), the delayed achievement of sterility (4% three months after vasectomy), chronic scrotalgia (5%) and the risk of recanalisation (0.28-00.5%) is of utmost importance. Moreover, the couple should be convinced that vasectomy can only be considered successful if less than 100,000 non-motile sperms per ml are demonstrated by a certified laboratory in a post-vasectomy semen analysis. As an alternative for vasectomy, several clinical studies to assess the value of male hormonal contraception are currently in progress.

[Revised guideline 'Vasectomy' from the Dutch Urological Association]. / Herziene richtlijn 'Vasectomie' van de Nederlandse Vereniging voor Urologie.

Vasectomy is a simple and reliable method of contraception. Problems associated with vasectomy include inadequate patient information, complications of the procedure e.g. infection and scrotal bleeding (4-22%), chronic scrotal pain after the procedure (2-5%) and spontaneous recanalisation with return of fertility (0.03-I12%). Later in life a substantial number of men come to regret having a vasectomy, notably those who underwent it at a young age and those without children of their own. After 10 years 2.4% of vasectomised Dutch men have a refertilisation procedure (usually a vasovasostomy) because of the wish for children in a new relationship. Since vasectomy is an elective procedure and not done on medical indication, it requires an extensive informed-consent procedure for the patient. Insufficient information may result in inadequate follow-up, omission of semen analysis, and consequent legal procedures should complications or pregnancy ensue. Clearance after the first semen analysis at 3 months can be given if azoospermia is seen or if less than 100,000 non-motile spermatozoa are present in the ejaculate.

[No arguments to support an age limit for men entering an in vitro fertilisation or intracytoplasmic sperm injection programme]. / Geen onderbouwing voor maximale leeftijdsgrens voor mannen bij in-vitrofertilisatie of intracytoplasmatische sperma-injectie.

OBJECTIVE: To identify medical and psychosocial risks that could arise from allowing older men to father children through in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). DESIGN: Literature review. METHOD: The databases Medline, Current Contents weekly, Current Contents archives, and PsycINFO were searched over the period 1970--June 2004 for articles with data on age limits for men entering IVF/ICSI programmes. The following inclusion criteria were used: availability in the Netherlands and written in English or Dutch. RESULTS: Although sperm quality decreases with age, men remain fertile up to an advanced age. The risks of having children with autosomal dominant disorders or chromosomal defects increase slightly, but the individual chance is extremely small. Studies on the psychological development of children with fathers aged > 50 years are lacking. Extrapolation from other studies indicates that growing up with an older father has no negative influence on child development. Although older fathers have a greater chance of dying sooner, the absence of the father does not contribute significantly to psychological problems in offspring later in life. CONCLUSION: There are no medical or psychosocial arguments to support an age limit for men entering an IVF/ICSI programme.

Time course of proteinuria after living-donor kidney transplantation.

BACKGROUND: After cadaveric kidney transplantation, preservation-reperfusion damage results in glomerular and tubular proteinuria. There are no data on the time course of proteinuria after living-donor (LD) transplantation. METHODS: In 10 patients receiving a kidney graft from an LD, the excretion of high molecular weight proteins (albumin, transferrin, and immunoglobulin G) and low molecular weight proteins (beta2-microglobulin and alpha1-microglobulin) was measured at various time points during the first 5 days after transplantation. RESULTS: Immediately after restoration of the circulation, we observed a massive nonselective high molecular weight proteinuria, indicative of glomerular damage. This proteinuria rapidly decreased to slightly elevated values beyond 24 hr after transplantation. Low molecular weight proteinuria, reflecting tubular damage, was also prominent and remained grossly abnormal even at day 5. CONCLUSION: After LD transplantation, preservation-reperfusion injury causes massive proteinuria during the first 24 hr. Thereafter proteinuria rarely exceeds 1 g per day.

Sexual dysfunction after renal replacement therapy.

The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.

Diagnosis and treatment of 409 patients with prostatitis syndromes.

We reviewed 409 patients who had prostatitis syndromes during the period 1985-1991. Urine analysis, x-ray film of abdomen, and sonograms of the kidneys did not contribute to the diagnosis of prostatitis. In 22 percent of the urine samples, slight-to-moderate atypia was seen in urine cytology but no malignancy was found. Uroflowmetry data were abnormal for 30 percent of the patients, and thus uroflowmetry may contribute to treatment selection of patients who may gain from specific drugs such as the newly developed alpha-1 receptor blocking agents. Positive bacteria cultures were found in 10.4 percent of the prostatic fluid cultures and in 14.3 percent of cultures of the urethra. Ureaplasma urealyticum was seen in 19.6 percent of the prostatic fluid cultures and in 32 percent of cultures of the urethra. Prostatic fluid cultures did not give additional information, and the outcome of semen cultures showed a poor correlation with urethra or prostatic fluid cultures. In this series, the most advocated treatment remains the antibiotic treatment (75% of patients) bringing relief of complaints in 35.6 percent of the patients and cure in 23.8 percent. However, similar results were found if no antibiotics were administered (relief of complaints in 31.6% and cure in 30.5%) and more than one course of antibiotics did not improve these results. Consequently, we advocate the use of specific antibiotics only when the causative bacterial agent has been identified.

Prevalence of erectile dysfunction: need for treatment?

Research examining the occurrence of sexual problems in nonclinical populations tends to be restricted to highly select populations. Recently, several population-based surveys surfaced in the international literature, triggered by the advent of effective pharmacological treatment for erectile dysfunction (ED). ED is a common disorder, especially among elderly men. The annual incidence in men 40-69 y of age is 26 per 1000 men. Although most of the difficulties are mild and do not totally prevent intercourse, about 26% of men experience moderate to complete ED. The impact of this category of ED on sexual activity among men is marked. The incidence of ED increases with age and the presence of concomitant conditions, such as diabetes mellitus, heart disease, hypertension, depression, pelvic surgery, negative mood, lack of self-esteem, problems with relationships, or just inadequate sexual experience. Vascular disease is thought to be the most common cause of organic ED, and it may be an early symptom of cardiac morbidity and mortality. Although one may expect that any man with ED who is motivated to continue sexual activity may seek current highly effective symptomatic medical treatment, only a few men are actually seeking help, and not every man seeking help appears to be a candidate for (symptomatic) medical treatment. The frequent association of sexual and medical problems, especially in the aged, and the high dropout rates for symptomatic ED treatment make counseling, adjustment of lifestyle, and modification of risk factors, such as medication, overweight, smoking, alcohol consumption, and lack of exercise, the primary steps in a holistic approach toward the treatment of ED. It is especially important to educate these men to remain physically and sexually as active as possible for as long as possible. The phrase 'use it or lose it' is particularly appropriate for the genitalia.

The post-investigation questionnaire (PIO-R): a practical instrument to assess erectile response after intracavernous injection.

Erectile response to intracavernous pharmacological stimulation is highly susceptible to stress and anxiety provoked by the test-situation. To reduce false-positive diagnosis of veno-occlusive dysfunction and to limit the need for high-dosage pharmacotesting, we developed the Post-Investigation Questionnaire (PIQ-R), a self-report instrument to assess erectile response to pharmacological stimulation after the patient has left the office. In this study veno-occlusive sufficiency was not demonstrated in 80 of 105 patients with erectile dysfunction at the time of pharmaco-penile duplex ultrasonography. PIQ-R detected sufficient erectile response in 40 of these patients, thus reducing false-positive diagnosis of veno-occlusive dysfunction by 50%. We also found that reports of sexual activity after investigation increased interest in auto-injection therapy. PIQ-R is a practical self-report measure to assess erectile response after clinical pharmacotesting, and to more carefully select patients for auto-injection therapy.

Sexual dysfunction in men with multiple sclerosis--a comprehensive pilot-study into etiology.

UNLABELLED: Ideally, the etiological diagnosis of sexual dysfunction in patients with multiple sclerosis is established on the basis of both objective and subjective tests. Accordingly, we assessed sexual function in 16 male patients with multiple sclerosis and complaints of sexual dysfunction by means of subjective data from interviews and questionnaires and objective data, obtained from (psycho)physiological tests. Psychophysiological investigation consisted of measurement of sleep erections and of erectile response to visual erotic stimulation and penile vibration. Urodynamic investigation was used to assess the neurological status of the genital tract. Sixteen male patients with clinically definite multiple sclerosis, complaints of sexual dysfunction and a steady heterosexual relationship participated in the study. The majority of patients had no abnormalities in the objective tests. Only one (1 out of 15) patient showed disturbed sleep-erections, and four (4 out of 12) other patients showed signs of neurological dysfunction of the genital tract. CONCLUSION: In our patient-group, disturbed sleep erections and abnormal findings on urodynamic investigation appeared unrelated to the complaint of erectile dysfunction. Sexual function was related to psychological factors, decreased general sensitivity, and motor impairment.

The use of acupuncture in the treatment of erectile dysfunction.

The efficacy of acupuncture as a mono-therapy was evaluated in a pilot study of 16 patients suffering from erectile dysfunction (ED). In nine patients no organic co-morbidity was encountered. In a period of four weeks, acupuncture treatment was performed twice a week for a total of eight sessions. Each treatment session consisted of puncture of the same eight acupoints, four of which were connected to a Swiss made constant current Doltron ESA 600 stimulator. Low frequency electrical stimulation (5 Hz and 10 mA) was applied to these four acupoints, whereas no stimulation was applied to the other four points. After 30min, the electrical stimulation was terminated and all needles removed. Blood samples were drawn according to a fixed time schedule, to study the profile of a number of stress hormones, for example, adrenocorticotropic hormone, antidiuretic hormone and cortisol, the gonadotrophines follicle stimulating hormone and leutinizing hormone, and the sex steroid testosterone and its binding globulin, within the treatment period. Based on a diary of both patient and partner, and an interview one month after the end of treatment, the changes of sexual activity were evaluated over a period of 12 weeks, starting from the four weeks prior to the treatment, the four weeks during the treatment period and the four weeks after the treatment. An improvement of the quality of erection was experienced by 15% of patients, while 31% reported an increase in their sexual activity. No changes in the profiles of hormones were detected. The use of acupuncture as a mono-therapeutic modality in ED, did not influence the profile of the stress and sex hormones, but did improve the quality of erection and restored the sexual activity with an overall effect of 39%. No definite conclusions can be drawn from this pilot study. A controlled and blinded study including more patients will be needed before any definitive conclusion can be reached.

The impact of marital satisfaction and psychological counselling on the outcome of ICI-treatment in men with ED.

We investigated the relationship between marital satisfaction and choice of and compliance with treatment in 195 consecutive men with erectile dysfunction (ED). Marital satisfaction as measured by means of the Maudsley Marital Questionnaire (MMQ), was compared between four groups: (1) patients on intracavernous injection (ICI) treatment after the trial-dose phase (32%); (2) patients dropped out ICI in the trial-dose phase (12%); (3) patients on other treatment (31%); and (4) patients following first counselling renounced treatment (25%). Above, in a small group of 15 patients the effect of ICI treatment in combination with short-term psychological counselling (ICI + treatment) was assessed. No significant differences were found in marital satisfaction between the four groups. In the ICI + treatment group we experienced that providing information about factors that contribute to erectile function and enabling couples to communicate about sexual problems were the most important factors to increase efficacy of ICI treatment.

Prognostic factors for the vascular components of erectile dysfunction in patients on renal replacement therapy.

A total of 76 male patients on renal replacement therapy (RRT) were investigated. Erectile dysfunction (ED) was defined as insufficient erection during visual erotic stimulation (VES) or during sleep as measured with Rigiscan and Erectiometer. Data on medical history, physical examination, and laboratory variables were collected. Furthermore, penile pharmacological duplex ultrasonography (PPDU) was performed. Univariate and multivariate logistic regressions were used to determine prognostic values and to develop prognostic models. Independent prognostic factors for ED were the number of cardiovascular events, waist-hip ratio, body mass index, and acceleration time (AT) as measured with PPDU. Independent prognostic factors for an abnormal AT (>100 ms) were number of cardiovascular events, age category, and the presence of carotid bruits. Independent prognostic factors for insufficient veno-occlusion during PPDU were number of cardiovascular events and supine diastolic blood pressure. The vascular contribution to ED in patients on RRT is substantial. Data from medical history, limited physical examination, and PPDU contribute to the prediction of the vascular contribution to ED.

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography.

The purpose of this work was to assess whether a single intracavernous injection (ICI) of a low dose of the combination of papaverine-phentolamine is replaceable by a high dose of the oral erectogenic agent sildenafil as mode of stimulation during pharmaco-penile duplex ultrasonography (PPDU). Eleven patients with complaints of erectile dysfunction were included in a crossover study. With an interval of two weeks the patients were exposed to ICI with papaverine/phentolamine (3.75 mg/0.125 mg) and oral administration with sildenafil (100 mg) preceding PPDU. Five patients started with ICI. Six patients started with sildenafil. In the sildenafil stimulation mode, visual erotic stimulation (VES) was used to initiate erection. VES was applied by personal LCD monitor. Cut-off values to define sufficient arterial response were: peak flow velocity (PSV) >25 cm/s and acceleration time (AT) <72 ms. Cut-off value to define sufficient veno-occlusion was a resistance index > or =1.00. Statistical analysis of PPDU parameters shows no significant difference between the two modes of stimulation for arterial response (PSV, AT), whereas the resistance index, as a parameter of veno-occlusive response was significantly higher in the sildenafil mode. This finding is confirmed in the clinical translation of the results: two patients with an insufficient arterial response to ICI had a sufficient arterial response to sildenafil and only one patient showed an insufficient arterial response following sildenafil, whereas the response following ICI was sufficient. Analysis of veno-occlusive responses shows remarkable differences between both modes of stimulation. Whereas following the administration of sildenafil all veno-occlusive responses were classified as sufficient, seven patients showed an insufficient veno-occlusive response following ICI. As mode of stimulation in PPDU, high dose sildenafil yields significantly less false positive diagnoses of 'veno-occlusive dysfunction' than intracavernous injection of the combination papaverine/phentolamine. No difference was found in the quality of the arterial response. Based on this study we conclude that sildenafil may replace ICI as mode of stimulation during PPDU.

Incidence and determinants of sildenafil (dis)continuation: the Dutch cohort of sildenafil users.

Sildenafil utilization was prospectively evaluated among 153 men with a history of erectile dysfunction (ED)-prescription drug use prior to starting sildenafil and 164 men who were new starters of ED-prescription drugs. Further, some determinants of sildenafil discontinuation were identified. During a median follow-up period of 18 months 45% of all patients discontinued sildenafil treatment, regardless of earlier treatment history. However, patients with a history of drug treatment for ED were nearly eight times as likely to switch or re-start another ED-prescription drug after discontinuing sildenafil compared to previously untreated users. Age >60 y, diabetes medication, nitrate use, and use of incontinence pads (a proxy for disease/surgery in the pelvic region) were associated with an increased likelihood of discontinuing sildenafil. Although the introduction of sildenafil reduced the barrier to seek medical help for erectile problems, sildenafil treatment failure in previously untreated patients results in a high dropout rate from further ED drug treatment of any kind.

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Mutation frequency of cystic fibrosis transmembrane regulator is not increased in oligozoospermic male candidates for intracytoplasmic sperm injection.

OBJECTIVE: To examine the frequency of anomalies of the vas deferens and the frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in male candidates for intracytoplasmic sperm injection (ICSI) who had severe oligoasthenoteratozoospermia. DESIGN: The clinical data for male candidates for ICSI were studied. The three most frequent cystic fibrosis (CF)-causing CFTR mutations in the Dutch population (deltaF508, A455E, and G542X) and the three most frequent CFTR mutations potentially causing congenital bilateral absence of the vas deferens (CBAVD) in the Dutch population (deltaF508, R117H, and IVS8-5T) were analyzed. Delta I507 is also detected by the deltaF508 test. Samples of DNA from patients identified as CFTR mutation carriers were subjected to denaturing gradient gel electrophoresis analysis with use of a two-dimensional electrophoretic technique. SETTING: University-based center for reproductive medicine and clinical genetics. PATIENT(S): Male candidates for ICSI who had oligoasthenoteratozoospermia and no history of operative sterilization and refertilization. Males with a chromosomal aberration or a Y-chromosome microdeletion were excluded. INTERVENTION(S): Semen and blood samples were collected from the patients at their first visit to the clinic. MAIN OUTCOME MEASURE(S): Frequency of anomalies of the vas deferens and frequency of mutations of the CFTR gene in male candidates for ICSI who had oligoasthenoteratozoospermia. RESULT(S): None of the patients had abnormalities of the vas deferens at physical examination. In 4 of the 150 chromosomes (75 patients), a CFTR mutation was found, yielding a CFTR mutation frequency of 2.7% (95% confidence interval, 1.0-6.7%). None of the patients had two CFTR mutations. CONCLUSION(S): The frequency of congenital abnormalities of the vas deferens in patients with oligoasthenoteratozoospermia is low. The frequencies of the CFTR mutations identified in this cohort did not differ significantly from the frequencies found in the normal Dutch population.

Investigation of erectile dysfunction. Diagnostic testing for vascular factors in erectile dysfunction.

To date, several accurate tests for diagnosing vascular ED may be chosen. It is necessary to be well aware of the purpose of testing: global assessment of erectile capacity in preparation for auto-injection therapy, or detailed assessment of arterial and erectile response in preparation for surgical treatment. Pharmacotesting may be sufficient for the majority of patients. Other, more invasive tests are reserved for preparing surgical treatment or scientific studies.