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.

Diagnostic approach in patients with asymptomatic haematuria: efficient or not?

Many patients with asymptomatic haematuria are primarily referred to urological examination. To analyse the efficiency of this strategy, we investigated the diagnostic process in 134 patients with asymptomatic haematuria (91 macroscopic and 43 microscopic) who were referred to our urology department. The frequency of diagnostic procedures was urine culture: 91%, cystoscopy: 87%, intravenous urography: 86%, ultrasound: 73%, examination of urinary sediment: 20%. In 70 patients (52%), a urological diagnosis was made. In the remaining 64 patients, the urinary sediment was examined for the presence of dysmorphic erythrocytes and erythrocyte casts in 17 patients (27%). Signs of glomerular haematuria were found in nine of them (53%). The diagnostic strategy in these patients with asymptomatic haematuria was not discordant from several published algorithms but appeared neither efficacious nor efficient. We estimate that when examination of the urinary sediment would have been performed at the start of work-up, 25% of patients could have spared from extensive urological investigation.

[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.

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.

[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.

The methodology of corpus cavernosum electromyography revisited.

OBJECTIVE: The methodology of corpus cavernosum electromyography (CC-EMG) was revisited, in order to overcome current methodological difficulties that hinder its clinical application. MATERIALS AND METHODS: Using an 8-channel device, CC-EMG was performed in 12 healthy volunteers. Surface electrodes were placed bilaterally on the penile shaft and the kneecap (reference electrode), the pubis region and the anterior superior iliac spine (ASIS). A band pass filter with cut-off frequencies of 0.1 and 20 Hz was used. At least 2 sessions of recordings were performed in each subject. RESULTS: Thirty-five of 46 recordings were interpretable. Significant time delays between potentials recorded from different sites of the CC were detected. Clear spatial voltage gradients related to CC-potentials were observed on the pubis region. No voltage changes related to CC-potentials, but electrical activity from other sources were recorded from the ASIS. In contrast to frequency, a clear correlation could be demonstrated between amplitude, duration and polyphasity of CC-potentials recorded in 2 different sessions in the same individual. CONCLUSIONS: Multichannel monopolar recording of CC-EMG with surface electrodes is practical and has several advantages compared with bipolar recording. The results provide evidence that the recorded signals indeed reflect electrical activity of the CC and therefore offer a basis to pursue further clinical validation studies.

Percutaneous epididymal sperm aspiration: a diagnostic tool for the prediction of complete spermatogenesis.

The classification of azoospermia into obstructive or non-obstructive is largely based on medical history, physical examination and biochemical markers in serum and semen. However, the most accurate parameter for diagnosis is the testicular histology. The predictive value of the percutaneous epididymal sperm aspiration (PESA), FSH, LH, testosterone, inhibin-B and testicular volume was investigated for their accuracy to predict a complete spermatogenesis (Johnsen score > or =8) in order to replace the testicular histology. The specificity and sensitivity of FSH, inhibin-B, LH, testosterone, testicular volume, and the presence of sperm in a PESA procedure was evaluated in 147 azoospermic males attending the centre for infertility diagnosis. A positive PESA outcome presented the highest sensitivity and specificity to predict a Johnsen score > or =8 (93 and 94% respectively) compared with FSH (90 and 19%), inhibin-B (88 and 57%) and testicular volume (95 and 45%). Differences in clinical presentation were observed between patients with positive sperm retrieval with PESA, depending on the aetiology of obstruction. In conclusion, the presence of spermatozoa in the epididymis (PESA+) correlates with a Johnsen score > or =8 and is the most accurate parameter to predict complete spermatogenesis compared with clinical or biochemical parameters. Between obstructive azoospermic patients, the clinical parameters observed varied according to the aetiology.

Chromatin condensation and DNA damage of human epididymal spermatozoa in obstructive azoospermia.

Obstructive azoospermia (OA) includes patients with different aetiologies of obstruction such as congenital bilateral absence of vas deferens (CBAVD), post-vasectomy/failed vaso-vasostomy, or unknown (idiopathic). The frequency of DNA-damaged spermatozoa and abnormal chromatin condensation in epididymal spermatozoa of OA patients was investigated for the different aetiology subgroups. DNA damage in caput epididymis spermatozoa was assessed with the TdT-UTP nick-end labelling (TUNEL) assay and chromatin condensation status was measured with chromomycin A3 (CMA3) stain (n = 60 patients). All epididymal sperm samples showed high levels of TUNEL positivity (mean and SD, 43 +/- 17%). CMA3 rates showed large variation within the samples (mean and SD, 53 +/- 21%, range 7-97%); however, a significant difference in chromatin condensation was found between the different aetiologies of obstruction. The highest percentage of CMA3 positivity was found in the CBAVD and idiopathic groups (60 +/- 17 and 65 +/- 18% respectively) compared with the post-vasectomy samples (37 +/- 17%) or ejaculated spermatozoa from normozoospermic males (29 +/- 12%). In conclusion, despite the normal testicular histology in OA men, chromatin condensation differed between OA patients. The physiological heterogeneity found in chromatin condensation between patient subgroups is probably influenced by the aetiology of the obstruction.

The risk of coronary heart disease in men with erectile dysfunction.

OBJECTIVES: Erectile dysfunction (ED) is a common disorder of aging male and about 50% of the ED sufferers consult a physician in the Netherlands. As ED is strongly correlated with cardiovascular diseases, we explored how many patients with ED aged 40 to 69 years will develop cardiovascular disease in the Netherlands and, philosophize if and which preventive measures are available to reduce cardiovascular risks in this specific population. METHODS: 158 patients were included and were comprehensively evaluated. All patients underwent a penile-pharmaco duplex ultrasonography to evaluate the penile vascular status and a cut-off value for acceleration time of 100 ms was used to distinguish between patients with and without cavernous arterial insufficiency. Framingham risk functions were used to determine the 4 to 12 year coronary heart disease risk. The results were extrapolated to the Dutch ageing male population. RESULTS: In the age group 40 to 49 years and 60 to 69 years no significant difference was detected in coronary heart disease risk between patients with and without cavernous arterial insufficiency. In the age group 50 to 59 years patients with cavernous arterial insufficiency showed a significantly increased risk to develop coronary heart disease. It is estimated that in total, more than 25,000 ageing men with ED will develop coronary heart disease within 4 years and increases to almost 75,000 men within 12 years in the Netherlands. CONCLUSIONS: Screening on cardiovascular risk factors and taking preventive measures is recommended in men with ED. Men with cavernous arterial insufficiency aged 50 to 59 years are especially prone to develop coronary artery disease.

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.

The value of corpus cavernosum electromyography in erectile dysfunction: current status and future prospect.

In the last decade, several investigators have tried to develop corpus cavernosum electromyography (CC-EMG) as a direct clinical method to evaluate the state of the penile autonomic innervation and the cavernous smooth muscle. Both basic and clinical studies have shown promising results. However, its application as a diagnostic tool with clinical relevance was hindered by insufficient knowledge of cavernous smooth muscle electrophysiology, lack of standardization, technical and practical difficulties and problems in the interpretation of the results. Recently, the European Commission created the so-called COST Action B18 (corpus cavernosum EMG in erectile dysfunction), aiming to strengthen the coordination of the European research groups and give the development of CC-EMG a new impetus. This review presents an overview of the physiological background, the current status of CC-EMG, and discusses possibilities for further developments.

Erectile function after radical prostatectomy: a review.

OBJECTIVES: Although the high rate of erectile dysfunction (ED) following prostatectomy is well recognised, the aetiology and pathophysiology have not yet been fully elucidated. We examined the current literature as to aetiology, treatment and possible prevention of ED following prostatectomy. METHOD: Review of the literature by a Medline search. CONCLUSION: The most important predictors of erectile function are pre-operative erectile function and the nerve sparing nature of the procedure. The former is determined by age and vascular risk-factors whereas the latter is decided by the stage of the tumour and the skill of the surgeon. The value of intraoperative nerve mapping seems limited and the importance of nerve grafting is uncertain. Natural recovery of erection can take as long as 24 months. Patients complain about a lack of professional support. Symptomatic therapy may be applied according to the current general standards of treatment in men with ED.

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.

Penile duplex pharmaco-ultrasonography revisited: revalidation of the parameters of the cavernous arterial response.

PURPOSE: We revalidate parameters of the cavernous arterial response (peak systolic blood flow velocity) and acceleration time using penile duplex pharmaco-ultrasonography. MATERIALS AND METHODS: Blood flow velocity in the cavernous artery following pharmaco-stimulation was determined with duplex ultrasonography in 106 patients with erectile dysfunction. Intima media thickness of the common carotid artery, a valid index for atherosclerosis and clinical diagnosis based on a comprehensive evaluation were used as references. The clinical diagnosis was used to determine cutoff values. For the statistical analysis, Pearson correlation and ROC curves were used. RESULTS: When correlating peak systolic velocity and acceleration time to intima media thickness, acceleration time (r = 0.51, p <0.01) was the most valid parameter to detect cavernous atherosclerotic pathology (peak systolic velocity r = -0.18, p = 0.12). This finding was confirmed by a comparison of both parameters to the clinical diagnosis. AUC was 0.59, 95% CI 0.49-0.69 for peak systolic velocity and 0.72 (95% CI 0.62-0.80 for acceleration time). The cutoff point for acceleration time to discriminate between atherosclerotic and nonatherosclerotic erectile dysfunction was determined at acceleration time 100 milliseconds or greater. Sensitivity was 66% and specificity was 71%. CONCLUSIONS: The results of this study show that acceleration time has more power than peak systolic velocity to diagnose atherosclerotic erectile dysfunction.

[Obstructive azoospermia in men who wish to father children; diagnosis and surgical sperm retrieval]. / Mannen met obstructieve azoöspermie en kinderwens; diagnostiek en chirurgische spermawinning.

OBJECTIVE: To evaluate diagnostic procedures and surgical sperm retrieval in men with suspected obstructive azoospermia who wish to father children. DESIGN: Descriptive, retrospective. METHOD: During the period 1 April 1999-31 December 2001 93 men suspected of having obstructive azoospermia underwent surgical sperm retrieval by means of percutaneous epididymal sperm aspiration (PESA). In each patient a testicular biopsy was performed to determine the Johnsen score (a score > or = 8 is equivalent to a normal spermatogenesis). Cryopreservation was performed whenever possible. The findings in both percutaneous and surgical sperm retrieval were compared. RESULTS: In 76 patients (82%) epididymal motile sperm were obtained using PESA. Their Johnsen score on the testis biopsy was 9.1 (range: 7.4-10). In 73 of the patients the Johnsen score was > or = 8. In the 17 patients (18%) in whom no sperm were found with PESA, the median Johnsen score was 5.8 (range: 2-9.8). Epididymal sperm were not found in patients with a testicular volume < 15 ml. In all 28 patients who had undergone a vasectomy in the past, motile sperm were found along with a Johnsen score > or = 8. In 23 of the 24 patients with congenital bilateral absence of the vas deferens (CABVD) the Johnsen score was > or = 8. Cryopreservation was possible in 45 (59%) of all patients and in 5 (35%) of the 13 patients with an unknown cause for the obstructive azoospermia. CONCLUSION: In men with suspected obstructive azoospermia in whom sperm were found using PESA, a diagnostic testis biopsy provided no additional relevant information about the spermatogenesis. There was always a good spermatogenesis after vasectomy. CBAVD patients probably had at least some focal areas in the testes with normal spermatogenesis. Sperm retrieval and cryopreservation could be carried out less frequently in the case of obstructions with an unknown cause.

[Obstructive azoospermia in men who wish to father children; initial clinical results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen]. / Mannen met obstructieve azoöspermie en kinderwens; eerste klinische resultaten van intracytoplasmatische sperma-injectie met chirurgisch verkregen zaad.

OBJECTIVE: To evaluate the results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen. DESIGN: Prospective, descriptive. METHODS: Patients with an obstructive azoospermia confirmed by cytological examination of a testis biopsy, and conforming to the regular IVF/ICSI criteria as laid down in 2001 at the University Medical Centre St Radboud Nijmegen, the Netherlands, were included for percutaneous epididymal sperm aspiration (PESA) and ICSI. The main outcome measure was the ongoing pregnancy rate per initiated cycle. RESULTS: A total of 44 cycles were started in 31 couples. In 43 cases (98%) an ovum pick-up was performed and 41 (93%) embryo transfers were carried out. In 19 (43%) cases, treatment resulted in a positive pregnancy test and 15 (34%) ongoing pregnancies were recorded. In total, 17 healthy children were born (11 boys and 6 girls). CONCLUSION: ICSI with surgically retrieved semen was successfully used as a treatment for childlessness caused by obstructive azoospermia.

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.