Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis.

Despite differences in design, many large epidemiological studies using well-powered multivariate analyses consistently provide overwhelming evidence of a link between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Preclinical evidence suggests that several common pathophysiological mechanisms are involved in the development of both ED and LUTS. We recommend that patients seeking consultation for one condition should always be screened for the other condition. We propose that co-diagnosis would ensure that patient management accounts for all possible co-morbid and associated conditions. Medical, socio-demographic and lifestyle risk factors can help to inform diagnoses and should be taken into consideration during the initial consultation. Awareness of risk factors may alert physicians to patients at risk of ED or LUTS and so allow them to manage patients accordingly; early diagnosis of ED in patients with LUTS, for example, could help reduce the risk of subsequent cardiovascular disease. Prescribing physicians should be aware of the sexual adverse effects of many treatments currently recommended for LUTS; sexual function should be evaluated prior to commencement of treatment, and monitored throughout treatment to ensure that the choice of drug is appropriate.

PDE5 inhibitors in the treatment of LUTS.

Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS and the degree of erectile difficulty. Four pathophysiologies have been suggested to explain the relationship between LUTS and ED. There is a complex interaction between these mechanisms and there may be additional processes involved. These are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3) changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature atherosclerosis. Studies of all three easily available PDE-5 inhibitors have shown improvements in both LUTS and ED in men with significant problems in both areas without any substantial increase in side effect profile. Studies have also shown that the greatest improvements occurred with the combination of an alpha blocker and PDE-5 inhibitor when compared with either drug alone. Whilst significant improvements were seen in LUTS symptom scores, there was no significant improvement in flow rates with PDE-5 inhibitors when compared with placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle and alpha blocker agents on penile cavernosal tissue have provided several explanations for their modes of action. Even so, the mechanism of action of PDE-5 inhibitors in LUTS remains far from certain. More well-designed, placebo-controlled studies are needed to confirm the impact of these drugs, alone or in combination, on both ED and LUTS. However combination therapy appears appropriate for patients with both LUTS and ED. At present though, we should not routinely offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of LUTS alone.

Integrating partners into erectile dysfunction treatment: improving the sexual experience for the couple.

INTRODUCTION: Erectile dysfunction (ED) is a common condition estimated to affect more than 150 million men worldwide. ED should be regarded as a shared sexual problem which has significant detrimental effects both on the men who experience this condition and on their partners. EVIDENCE TO SUPPORT PARTNER INVOLVEMENT IN ED THERAPY: Evidence shows that the partner plays a key supportive role in the man's ED treatment and in successful long-term ED therapy. Including the partner in consultations may highlight discordant attitudes and communication problems between couple members which may indicate treatment acceptance or rejection, or realistic or unrealistic treatment expectations. OPTIONS FOR PARTNER INVOLVEMENT IN ED THERAPY: Most patients with ED consult their physician in the absence of their partner. Therefore, involving the partner in therapy can be challenging. Two options which physicians should consider are: encouraging the patient to bring the partner into the office and, often more realistically, seeking information about, and providing information to, the partner, via the patient. OBJECTIVES: The objective of these recommendations is to provide practical guidance on treating couples affected by ED, and suggest techniques that may be helpful in integrating the partner into the process of ED treatment.

Splenogonadal fusion - not just another hydrocoele.

Splenogonadal fusion is a rare congenital abnormality. In this case report, the diagnosis of splenogonadal fusion was made after the removal of an abnormal mass at 'routine' left herniotomy. A cautious approach at surgery resulted in no apparent damage to the testicle. A short review of the literature is included.

Nephrostomies in obstructive uropathy; how should hormone resistant prostate cancer patients be managed and can we predict who will benefit?

Current opinion advocates the use of nephrostomies in hormone naive patients with obstructive uropathy while hormone resistant patients require an individual approach. Patients undergoing a nephrostomy for uropathy were retrospectively analysed, with particular interest in hormone status and blood levels. Over a 46-month period, 26/112 nephrostomies were performed for prostate cancer induced uropathy. Survival was 226.5 days for hormone naive patients, 114.3 days in the responsive group and 100.2 days if resistant. Bilateral cases survived 72.1 days versus 157.6 days for unilateral patients. All patients should be considered for nephrostomy despite their hormone status.

Behaviour and transit of tamsulosin Oral Controlled Absorption System in the gastrointestinal tract.

OBJECTIVE: To assess the in vivo behaviour, gastric emptying time and gastrointestinal transit of the new tablet formulation of tamsulosin which uses the Oral Controlled Absorption System (OCAS) technology and to relate gastrointestinal transit parameters to the profile of the plasma concentration time curve. RESEARCH DESIGN AND METHODS: After breakfast, 8 healthy male subjects received a single tamsulosin OCAS 0.4 mg tablet labelled with 4MBq technetium-99m. Scintigraphic images were taken immediately after dosing, every 15 min until 15 h post-dose and at 24 h post-dose. Blood samples for pharmacokinetic analysis were taken up to 24 h after dosing. Safety was assessed by physical examinations, vital signs, laboratory safety evaluations and adverse events monitoring. RESULTS: A mean C(max) of 7.84 +/- 2.54 ng/mL was achieved after 5.13 +/- 1.25 h (t(max)). The mean gastric emptying time for the tablet was 4.1 +/- 2.5 h. Mean transit time through the small intestine was 3.6 +/- 2.9 h; the mean colonic arrival time 7.7 +/- 2.9 h post-dose and the mean release time (spread of the technetium-99m label from the tablet core) 12.3 +/- 1.7 h post-dose. In all cases where release of the radiolabelled tablet was observed, this occurred within the colon. Variations in gastric residence, small intestinal transit or colonic residence did not apparently influence release time or site. CONCLUSIONS: The results suggest that tamsulosin is released from the OCAS formulation throughout the entire gastrointestinal tract, including the colon, indicating consistent and continued 24-h drug release. This correlates with a more consistent pharmacokinetic profile.

Integrating risk profiles for disease progression in the treatment choice for patients with lower urinary tract symptoms/benign prostatic hyperplasia: a combined analysis of external evidence and clinical expertise.

The RAND appropriateness method was used to explore the relevance of risk factors for disease progression in the treatment choice for patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). A total of, 12 international experts assessed the appropriateness of various treatments for 243 risk profiles. Highest appropriateness rates were found for alpha1-adrenoceptor antagonists (68% of profiles) and combination therapy (46%). A large prostate volume was the dominant argument in favour of 5alpha-reductase inhibitors and combination therapy, but was irrelevant for the choice of surgery. Considerable postvoid residual, severe symptoms and poor maximum flow rate were the most important factors in favour of surgery.

Risk factors for disease progression in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH): a systematic analysis of expert opinion.

Disease progression has become an important issue for the management of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Although several risk factors have been identified, no specific patient risk profiles have been established that can be useful in the day-to-day management of LUTS/BPH. In this study, an international panel of urologists developed a risk classification based on the attribution of a risk score to 243 unique patient profiles. From the perspective of clinical decision making, it was concluded that postvoid residual, symptom severity and maximum flow rate are the most relevant determinants of the risk of disease progression.

An unusual presentation of genitourinary schistosomiasis in a Caucasian woman in the UK.

A young woman who presented with loin pain and pyuria after a prolonged period of investigations and treatment, finally having a nephrectomy for non-functioning kidney, was revealed to have schistosomial infestation with an adult worm in the ureter. Unusually, she only developed bladder manifestations later.

Primary adenocarcinoma of the rete testis.

We report a case of adenocarcinoma of the rete testis in a 44-year-old man, presented intially with a hydrocele and later with signs of infection in the affected hemiscrotum. Multiple focal lesions within the testis appeared 6 months later in ultrasounds. After high inguinal orchiectomy, histology revealed a primary adenocarcinoma of the rete testis. Adenocarcinoma of the rete testis is a rare a highly malignant tumour originating in the mediastinum of the testis. Slightly over 40 cases have been reported in the literature. The treatment of choice is radical orchiectomy. Prognosis is poor; as mainly as 40% of patients die within the first year of diagnosis.

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Estimating a population's needs for the treatment of lower urinary tract symptoms in men: what is the extent of unmet need?

BACKGROUND: Prevalence surveys have shown that men aged over 40 commonly experience lower urinary tract symptoms (LUTS). However, such studies cannot be used in isolation to inform health service planning, as not all men are troubled by their symptoms nor would they necessarily benefit from treatment. METHODS: A total of 3,540 randomly selected men in Somerset were sent a postal questionnaire containing the American Urological Association (AUA) symptom index. Men reporting moderate or severe symptoms were invited for clinical assessment to determine whether they could benefit from treatment in primary or secondary care. The impact of their symptoms on their quality of life was measured using the ICS-QOL questionnaire. RESULTS: The prevalence of reported LUTS was 256 per 1,000 men aged 40 and over. Of men reporting moderate or severe urinary symptoms, 40 per cent considered that they did not interfere with their life at all. The results were used to estimate the number of men with moderate or severe urinary symptoms, who could benefit from treatment and whose symptoms affected their quality of life. In a population of 250,000, 482 men [95 per cent confidence interval (CI) 263-704] could benefit from treatment in secondary care, and 3,557 men could be managed in primary care through watchful waiting or medical intervention (95 per cent CI 2,935-4,182). CONCLUSIONS: The majority of men with LUTS in the community are not greatly troubled by them and are unlikely to benefit from treatment. This work can be used as a basis for planning the provision of services across primary and secondary care for the treatment of this common condition.

Lower urinary tract symptoms suggestive of benign prostatic obstruction: what is the available evidence for rational management?

Because of the need for a more rational management of LUTS suggestive of BPO, EBM is receiving more attention. Treatment decisions should be based on scientific evidence more than on personal preferences of physicians and patients. EBM is more than following rigid treatment guidelines or published advice. It is a process of turning problems of clinical practice into well-defined questions and then finding and appraising available evidence and implementing it into clinical practice. In cases of LUTS suggestive of BPO, much evidence is available on the efficacy and tolerability of different treatment modalities in the short term, whereas long-term data on (cost)-effectiveness are rather scarce. From a patient's point of view, newer pharmacotherapeutic agents can be considered as an appropriate treatment option. alpha(1)-Adrenoceptor antagonists seem to be more efficacious than finasteride and within this group of drugs, selective alpha(1A)/alpha(1D)-adrenoceptor antagonists particularly show a favourable efficacy/tolerability ratio.

Initial choices and final outcomes in lower urinary tract symptoms.

Management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) requires careful thought so that the most appropriate treatment can be targeted to each individual patient. Initial choices in the management of LUTS/BPH include watchful waiting, medical therapies and surgical interventions. A decision on treatment choice should be taken together with the patient. It should be based on the best available scientific evidence but also be individualised to patients' circumstances and personal choices. Management of LUTS/BPH should be focused on the burden and impact of urinary symptoms and related quality of life. The rate of treatment failure, which can be assessed through the switch to other medical therapy or surgery and/or the delay or prevention of complications related to LUTS/BPH, is also important. Beneficial effects of treatment should be balanced against the incidence of adverse events associated with therapy. Medical therapy has been shown to be effective in improving short-term outcomes (maximum urinary flow rate and symptom scores). Increasing evidence indicates that in the long-term more selective alpha(1)-adrenoceptor (AR) antagonists such as alfuzosin and tamsulosin may reduce the risk of treatment failure with a comparable rate to finasteride. Although the different alpha(1)-AR antagonists are equivalent in efficacy they differ in tolerability with the subtype selective tamsulosin having the lowest risk for interference with blood pressure regulation. Transurethral resection of the prostate (TURP) improves storage symptoms to a lesser extent and/or more slowly than it improves voiding symptoms. In contrast, alpha(1)-AR antagonists improve both voiding and bothersome storage symptoms to the same extent and quite rapidly which has a considerable impact on quality of life. alpha(1)-AR antagonists also relieve storage symptoms to almost the same extent as TURP. Ultimately the initial choice of treatment will depend upon its efficacy, speed of onset, durability, tolerability and on patients' choice. For the majority of patients with moderate to severe symptoms a subtype selective alpha(1)-AR antagonist such as tamsulosin offers the best current combination of efficacy and tolerability.

Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation.

OBJECTIVES: The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF165) in the border zone of myocardial infarct tissue in rat hearts were investigated. BACKGROUND: Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium. METHODS: Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 +/- 6.5 days, the rats were injected with phVEGF165 at one location and control plasmid at a second location (500 microg DNA, n = 24) or saline (n = 16). After 33.1 +/- 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres. RESULTS: phVEGF165-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF165-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF165-treated hearts revealed 44.4 +/- 10.5 vascular structures per field in phVEGF165-treated hearts versus 21.4 +/- 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF,165-treated hearts (0.9 +/- 0.2) and saline-treated hearts (0.7 +/- 0.1). CONCLUSIONS: Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.

A new model of ventricular plication: a suturing technique to decrease left ventricular dimensions, improve contractility, and attenuate ventricular remodeling after myocardial infarction in the rat heart.

BACKGROUND: The Batista procedure (cardio-reduction) is a surgical technique in patients with dilated cardiomyopathy that results in improvement of ventricular function. The purpose of this study was to test a new suturing technique without resection for cardio-reduction of myocardial infarct scars in rats. METHODS AND RESULTS: Myocardial infarction (MI) was induced by occluding the left coronary artery 4 weeks before enrollment. Animals then were randomized to a control (n = 11) or treatment group (n = 11). A pursestring suture was placed within the border zones of the infarcted area and was either tightened (treated) or not (controls). Echocardiography was used to measure left ventricular diameters before, 1 hour, and 6 to 7 weeks after plication. Acutely after plication, end-diastolic length (EDL) decreased from 0.70 +/- 0.03 cm to 0.53 +/- 0.02 cm, P < .001; end-systolic length (ESL) decreased from 0.51 +/- 0.03 cm to 0.23 +/- 0.02 cm, P < .001; and fractional shortening (FS) increased from 27.6 +/- 1.5% to 57.6 +/- 2.3%, P < .001, whereas controls were unchanged. In control rats EDL increased from baseline at 0.73 +/- 0.02 cm to 0.82 +/- 0.04 cm at 6 weeks postsurgery, P < .05; ESL increased from 0.54 +/- 0.02 cm to 0.66 +/- 0.04 cm, P < .005; and FS decreased from 26.9 +/- 1.1% to 19.2 +/- 1.2% at 6 weeks, P < .05. In contrast, at 6 weeks in plicated animals, EDL was significantly less than controls at 0.64 +/- 0.02 cm, P < .005; ESL was significantly less than controls at 0.39 +/- 0.03 cm, P < .005, and FS was significantly better than controls at 40.5 +/- 2.2%, P < .005. CONCLUSION: The progressive LV enlargement between 4 and 10 weeks after MI reflects late ventricular remodeling. Plication by suturing infarcted tissue acutely decreases diameters and improves function. At 6 weeks, function remains improved over untreated animals.

Incidental presentation of leiomyoma of bladder with carincoma of the prostate.

We report a case of bladder leiomyoma found incidentally in a 66-year-old man during his work up for an adenocarcinoma of the prostate. Transrectal MRI scan appeared to be highly demonstrative of its localization and extent within the bladder wall. It was resected transurethrally.

Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology.

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing.