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Objective: Simulation is now firmly established in modern surgical training and is applicable not only to acquiring surgical skills but also to non-surgical skills and professionalism. A 5-day intensive Urology Simulation Boot Camp was run to teach emergency procedural skills, clinical reasoning, and communication skills using clinical scenario simulations, endoscopic and laparoscopic trainers. This paper reports the educational value of this first urology boot camp. Subjects and methods: Sixteen urology UK trainees completed pre-course questionnaires on their operative experience and confidence level in common urological procedures. The course included seven modules covering basic scrotal procedures, laparoscopic skills, ureteroscopy, transurethral resection of the prostate and bladder tumour, green light laser prostatectomy, familiarisation with common endoscopic equipment, bladder washout to remove clots, bladder botox injection, setting up urodynamics. Emergency urological conditions were managed using scenarios on SimMan®. The main focus of the course was hands-on training using animal models, bench-top models and virtual reality simulators. Post-course assessment and feedback on the course structure and utility of knowledge gained together with a global outcome score was collected. Results: Overall all the sections of feedback received score of over 4.5/5, with the hands-on training on simulators getting the best score 4.8/5. When trainees were asked “The training has equipped me with enhanced knowledge, understanding and skills,” the average score was 4.9/5.0. The vast majority of participants felt they would recommend the boot camp to future junior trainees. Conclusion: This first UK Urology Simulation Boot Camp has demonstrated feasibility and effectiveness in enhancing trainee’s experience. Given these positive feedbacks there is a good reason to expect that future courses will improve the overall skills of a new urology trainee.

Lymph node status is a key prognostic factor in penile cancer. The European Association of Urology (EAU) recommends intermediate-risk (pT1a, Grade 2) or high-risk (pT1b or greater) penile cancer patients with clinically non-palpable inguinal lymph node (cN0) to undergo either an invasive bilateral modified inguinal lymph node dissection (ILND) or dynamic sentinel node biopsy (DSNB). DSNB has been reported to have acceptable false negative rates, and lower rates of long-term morbidity compared to ILND. We developed a protocol for DSNB at a regional hospital in Singapore that was adopted from St James's University Hospital, Leeds Teaching Hospitals Trust. Four patients with cN0 penile cancer underwent DSNB between November 2021 and October 2022 according to this protocol. Our surgical technique and protocol are described. The patients' oncological characteristics and their outcomes were evaluated. In this small case series, there was no complication attributable to the performance of DSNB, and there was no groin that was documented to be false negative over a median follow up of 15.5 months (range, 12 to 22 months). Using our protocol, 5 of 8 groins (62.5%) were able to avoid ILND in the cN0 setting. We recommend the adoption of DSNB for the surgical staging of inguinal lymph nodes for patients with intermediate to high-risk penile cancer and non-palpable inguinal nodes due to its significantly lower risks of long-term morbidity compared to ILND. Appropriate specialist training and a multi-disciplinary team is vital to ensure the success of the procedure., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-681/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking., Objective: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex ® ; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women., Design: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year., Setting: Eight UK NHS secondary care sites., Participants: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial., Interventions: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted., Main Outcome Measures: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction., Results: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) ( p -value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) ( p  = 0.06). All other secondary outcomes and adverse events were similar in both arms., Limitations: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation., Conclusions: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics., Recommendations for Research: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics., Trial Registration: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Background: At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention., Design /methods: This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study., Discussion: The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study., Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

Objective: Education and training of surgeons has traditionally focused on the development of individual knowledge, technical skills and decision making. Knowledge about endoscopic instruments is one of the core elements of urological training. We assessed the precourse knowledge of newly appointed urology trainees and the impact of boot camp in improving their knowledge., Methods: Newly appointed specialty trainees in urology took part in a pilot 5-day urology simulation boot camp (USBC). The aim of the USBC was to improve their confidence, procedural performance and non-technical skills, with one of the modules looking at the trainees' knowledge about common endoscopic instruments in urology. Delegates were first asked to identify and assemble the instruments, followed by one-to-one teaching about the instruments. An Objective Structured Assessment Tool was used to assess their knowledge in the identification and assembly of the cystoscope, resectoscope and optical urethrotome, before and at the end of the course., Results: Data of two successive boot camps were collected to assess knowledge of instruments of newly appointed urology trainees. Majority of the trainees had good precourse knowledge of the cystoscopy kit, with 84% able to correctly identify the parts. Seventy-six per cent of candidates were able to identify the resectoscope equipment, but only approximately a third of trainees were able to correctly identify the urethrotome kit. The assembly of cystoscope, resectoscope and urethrotome was performed correctly in 74%, 42% and 32% at baseline and 94%, 90% and 77% postcourse, respectively. Overall performance improved significantly in the postcourse assessment (<0.001)., Conclusion: This urology boot camp has addressed gaps in trainees' core equipment knowledge and guided them to improve their knowledge with respect to identification and assembly of cystoscope, resectoscope and urethrotome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this work was to investigate the microbial causes, incidence, duration, risk factors and clinical implications of bacteraemia occurring during transurethral resection of the prostate (TURP) surgery to better inform prophylaxis strategies. An ethically approved, prospective, cohort study of patients undergoing TURP was conducted. Clinical information and follow-up details were collected using standardized data collection sheets. Blood was obtained for culture at 6 different time points peri-procedure. Standard of care antibiotic prophylaxis was given prior to surgery. Bacteriuria was assessed in a pre-procedure urine sample. Histopathology from all prostate chips was assessed for inflammation and malignancy. 73 patients were consented and 276 blood samples obtained. No patients developed symptomatic bacteraemia during the procedure, 17 patients developed asymptomatic bacteraemia (23.2%). Enterococcus faecalis and Pseudomonas aeruginosa were the most common organisms cultured. 10 minutes after the start of the TURP, the odds ratio (OR) of developing bacteraemia was 5.38 (CI 0.97-29.87 p = 0.05), and 20 minutes after the start of the procedure, the OR was 6.46 (CI 1.12-37.24, p = 0.03), compared to before the procedure. We also found an association between the development of intra-operative bacteraemia and recent antibiotic use (OR 4.34, CI 1.14-16.62, p = 0.032), the presence of a urinary catheter (OR 4.92, CI 1.13-21.51, p = 0.034) and a malignant histology (OR 4.90, CI 1.30-18.46, p = 0.019). There was no statistical relationship between pre-operative urine culture results and blood culture results. This study shows that asymptomatic bacteraemia is commonly caused by TURP and occurs in spite of antibiotic prophylaxis. Our findings challenge the commonly held view that urine is the primary source of bacteraemia in TURP-associated sepsis and raise the possibility of occult prostatic infection as a cause of bacteraemia. More work will be needed to determine the significance of transient bacteraemia in relation to more serious complications like infective endocarditis and malignancy.

Introduction: Varicocele is estimated to affect about 15% of the general male population. It usually occurs only on the left side, and is often asymptomatic. There is little evidence that varicocele reduces male fertility, although it is found in 12% of male partners of couples presenting with infertility and in 25% of men with abnormal semen analysis., Methods and Outcomes: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments in adult males with varicocele? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2013 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview)., Results: Searching of electronic databases retrieved 203 studies. After deduplication and removal of conference abstracts, 91 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 53 studies and the further review of 38 full publications. Of the 38 full articles evaluated, one existing systematic review was updated and two systematic reviews and five RCTs were added at this update. We performed a GRADE evaluation of nine PICO combinations., Conclusions: In this systematic overview we categorised the efficacy for four interventions, based on information relating to the effectiveness of embolisation, expectant management, sclerotherapy, and surgical ligation.

Aim: To explore the challenges of engaging men with penile cancer in qualitative interview research., Background: Qualitative interviewing offers an ideal tool for exploring men's experiences of illness, complementing and providing context to gendered health inequalities identified in epidemiological research on men. But conducting interviews with men can be challenging and embarking on a qualitative interview study with males can feel like a daunting task, given the limited amount of practical, gender-sensitive guidance for researchers. Reflecting on a researcher's experience of conducting qualitative research on men with penile cancer, this paper explores the potential challenges of interviewing this group, but also documents how engagement and data collection were achieved., Review Methods: This is a reflective paper, informed by the experiences of a male researcher (KW) with no nurse training, who conducted 28 interviews with men who had been treated for penile cancer. The researcher's experiences are reported in chronological order, from the methodological challenges of recruitment to those of conducting the interview., Implications for Practice/research: The paper offers a resource for the novice researcher, highlighting some advantages and disadvantages of conducting qualitative interview research as a nurse researcher, as well as recommendations on how to overcome challenges., Conclusion: Engaging men with penile cancer in qualitative interview raises practical, methodological, ethical and emotional challenges for the researcher. However, when these challenges are met, men will talk about their health. Methodological procedures must enable an open and ongoing dialogue with clinical gatekeepers and potential participants to promote engagement. Support from colleagues is essential for any interviewer, no matter how experienced the researcher is.

Background: There is an emerging association between ketamine abuse and the development of urological symptoms including dysuria, frequency and urgency, which have a neurological component. In addition, extreme cases are associated with severe unresolving bladder pain in conjunction with a thickened, contracted bladder and an ulcerated/absent urothelium. Here we report on unusual neuropathological features seen by immunohistology in ketamine cystitis., Results: In all cases, the lamina propria was replete with fine neurofilament protein (NFP+) nerve fibres and in most patients (20/21), there was prominent peripheral nerve fascicle hyperplasia that showed particular resemblance to Morton's neuroma. The nerve fascicles, which were positive for NFP, S100 and the p75 low-affinity nerve growth factor receptor (NGFR), were generally associated with a well-developed and in places, prominent, epithelial membrane antigen+/NGFR+ perineurium. This peripheral nerve fascicle hyperplasia is likely to account for the extreme pain experienced by ketamine cystitis patients. Urothelial damage was a notable feature of all ketamine cystitis specimens and where urothelium remained, increased NGFR expression was observed, with expansion from a basal-restricted normal pattern of expression into the suprabasal urothelium., Conclusions: The histological findings were distinguishing features of ketamine cystitis and were not present in other painful bladder conditions. Ketamine cystitis afflicts predominantly young patients, with unknown long-term consequences, and requires a strategy to control severe bladder pain in order to remove a dependency on the causative agent. Our study indicates that the development of pain in ketamine cystitis is mediated through a specific neurogenic mechanism that may also implicate the urothelium.

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca²⁺. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium. To evaluate the expression and function of P2X and P2Y receptors and TRP channels, the human ureter and bladder were used to separate urothelial and stromal tissues for RNA isolation and cell culture. RT-PCR using stringently designed primer sets was used to establish which P2 and TRP species were expressed at the transcript level, and selective agonists/antagonists were used to confirm functional expression by monitoring changes in intracellular Ca²⁺ and in a scratch repair assay. The results confirmed the functional expression of P2Y₄ receptors and excluded nonexpressed receptors/channels (P2X₁, P2X₃, P2X₆, P2Y₆, P2Y₁₁, TRPV5, and TRPM8), while a dearth of specific agonists confounded the functional validation of expressed P2X₂, P2X₄, P2Y₁, P2Y₂, TRPV2, TRPV3, TRPV6 and TRPM7 receptors/channels. Although a conventional response was elicited in control stromal-derived cells, the urothelial cell response to well-characterized TRPV1 and TRPV4 agonists/antagonists revealed unexpected anomalies. In addition, agonists that invoked an increase in intracellular Ca²⁺ promoted urothelial scratch repair, presumably through the release of ATP. The study raises important questions about the ligand selectivity of receptor/channel targets expressed by the urothelium. These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting.

Premature ejaculation (PE) is a common male sexual dysfunction. Advances in PE research have been hampered owing to a nonstandardized definition of PE, until the definition by the International Society of Sexual Medicine (ISSM) in 2009. Once the diagnosis of PE is established through a thorough history, a variety of medical therapies is available, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), centrally acting opiates, phosphodiesterase 5 inhibitors and topical desensitizing creams. Most of these treatments increase the intravaginal ejaculation latency time (IELT) and patient satisfaction scores, with the most convincing evidence for SSRIs and topical creams. Daily SSRIs such as paroxetine, although efficacious, do have a substantial and prolonged side effect profile. Dapoxetine, which is a on-demand SSRI, is the only licensed drug for the treatment of PE, increasing IELT by a factor of 2.5 to 3 with limited and tolerable side effects. In the near future, the topical aerosol PSD502 is due to be licensed for the treatment of PE, increasing IELT by up to a factor of 6 but having minimal local and negligible systemic side effects.

Introduction: A prospective study of postoperative oral and perineal pain experienced by a group of patients undergoing buccal mucosal graft harvest for urethral reconstruction., Patients and Methods: A consecutive group of 24 male patients undergoing buccal mucosa graft harvest for urethral reconstruction of stricture disease was prospectively studied between June 2006 and December 2008. All patients were examined pre-operatively and entered into the study prospectively. After surgery, all patients were reviewed at 24 h and 48 h. On both occasions, they were asked to complete a proforma containing visual analogue pain scales for both the oral donor site as well as the perineum., Results: A statistically significant higher level of pain was experienced from the perineum than the oral donor site on both the first and second postoperative days., Conclusions: Comparative analysis of visual analogue pain scale scores between oral donor site and perineum showed that patients experience significantly more pain from the latter postoperatively.

Purpose: Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. We have examined the prognostic significance of a large number of hematologic and biochemical variables, as well as traditional tumor-related factors in patients with RCC., Experimental Design: Patients undergoing nephrectomy for newly diagnosed RCC between September 1998 and March 2005 were invited to participate. Clinical, pathologic, and laboratory data were recorded in each case, and immunophenotyping was carried out on a subset of patients. A planned subset analysis of patients presenting with N0M0 disease was done., Results: Two hundred twelve patients with RCC formed the study population. In addition to tumor-related factors, multivariate analyses revealed preoperative serum sodium concentration to be independently and significantly associated with overall survival and disease-free survival when considered as both a continuous variable and when dichotomized to above and below the median value [139 mmol/L; reference range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22-0.88, P = 0.014]. Five-year overall survival estimates for patients above and below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI 32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis., Conclusions: We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to show that low preoperative sodium concentration may be an important factor associated with reduced survival in patients with RCC, suggesting that serum sodium should be considered with established prognostic variables in modeling survival in RCC.

Introduction: Acute epididymo-orchitis is a common and increasing problem. This retrospective study reviewed whether the European Association of Urology guidelines for the management of acute epididymo-orchitis, which form the basis of this Trust's present inter-departmental guidelines, are being effectively implemented., Patients and Methods: Case notes of 53 patients attending the emergency department with acute epididymo-orchitis over a 6-month period were reviewed retrospectively. The hospital results' database was used to confirm the diagnostic tests requested on patients at the time of their initial presentation., Results: Of the study cohort, 26 patients were aged 35 years. The results demonstrated that a sexual history was documented in only 43.4% of cases. A mid-stream urine sample was sent for routine culture in 54.7% of cases whilst urine for the Chlamydia polymerase chain reaction (PCR) test was obtained in 17% and a urethral swab performed in 5.6%. Antibiotics were prescribed in 81% of cases. Of these patients, 46.5% received ciprofloxacin alone (mean age, 52 years; range, 18-87 years), 25.5% received doxycycline alone (mean age, 30 years; range, 18-45 years) and 21% received both ciprofloxacin and doxycycline (mean age, 33 years; range 18-49 years). In 26.4% of cases, verbal advice to attend a genito-urinary medicine clinic was given, whilst a formal telephone referral was made in only one case. Formal urological follow-up was arranged for only three out of 11 patients aged > 50 years., Conclusions: Although a joint emergency department/urology clinical protocol for the investigation and treatment of acute epididymo-orchitis already exists within the Trust, our current management conforms to this in only a minority of cases. Many different strategies can be employed in the implementation of clinical practice guidelines and all are associated with variable degrees of success. The regular movement of junior staff through each department necessitates that the distribution of management protocols and guidelines occurs at frequent intervals throughout the year and that their implementation is continuously monitored so that, if necessary, further implementation strategies can be employed.

The urinary bladder and associated tract is lined by the urothelium. Once considered as just an impermeable epithelium, it is becoming evident that the urothelium not only functions as a volume-accommodating urinary barrier but has additional roles, including sensory signaling. Lack of access to normal human urothelium has hampered physiological investigation, and although cell culture systems have been developed, there has been a failure to demonstrate that normal human urothelial (NHU) cells grown in vitro retain the capacity to form a functional differentiated urothelium. The aim of this study was to develop a biomimetic human urothelium from NHU cell cultures. Urothelial cells isolated from normal human urothelium and serially propagated as monolayers in serum-free culture were homogeneous and adopted a proliferative, nondifferentiated phenotype. In the presence of serum and physiological concentrations of calcium, these cells could be reproducibly induced to form stratified urothelia consisting of basal, intermediate, and superficial cells, with differential expression of cytokeratins and superficial tight junctions. Functionally, the neotissues showed characteristics of native urothelium, including high transepithelial electrical resistance of >3,000 Omega.cm(2), apical membrane-restricted amiloride-sensitive sodium ion channels, basal expression of Na(+)-K(+)-ATPase, and low diffusive permeability to urea, water, and dextran. This model represents major progress in developing a biomimetic human urothelial culture model to explore molecular and functional relationships in normal and dysfunctional bladder physiology.

Aims: To determine the onset and duration of action of sildenafil in patients with erectile dysfunction (ED)., Methods: Two randomised, double-blind, placebo-controlled, two-way crossover studies were conducted in men with ED of no known organic cause. Study I: The time to onset of erections after sildenafil (50 mg) or placebo dosing following visual sexual stimulation (VSS) was assessed in 17 patients. Patients not achieving >60% penile rigidity by 70 min postdose as measured by a RigiScan(R) monitoring device were assigned an onset time of 70 min. Study II: The duration of grade 3 (hard enough for penetration) and grade 4 (fully hard) erections, determined by self-assessment during 60 min of VSS starting 2 and 4 h after sildenafil (100 mg) or placebo dosing, was measured in 16 patients., Results: Study I: The median time (range) to onset of erections was 27 min (in a range of 12--70) after receiving sildenafil 50 mg. In the sildenafil group, 71% of patients experienced onset of erections within 30 min of dosing, and 82% responded within 45 min. Of the patients who achieved >60% penile rigidity after sildenafil, 86% had done so by 30 min after dosing. Study II: When VSS began 2 h postdose, the median duration of grade 3 or 4 erections was 19.5 min (0--55) for sildenafil vs 0 min (0--23) for placebo. When VSS began 4 h postdose, the median duration was 5 min (0--45) for sildenafil compared with 0 min for placebo (0--27)., Conclusions: Sildenafil is an effective oral treatment for ED that produces a penetrative erection as early as 12 min and for most patients, within 30 min after dosing, and a duration of action lasting at least 4 h.

Background: Erectile dysfunction is a common, multi-factorial disorder., Aims: To evaluate the efficacy, tolerability and frequency of use of sildenafil citrate in men with mild to moderate erectile dysfunction of no established organic cause., Method: This double-blind, randomised, placebo-controlled, flexible-dose, two-way crossover study was conducted at four centres in the UK in 44 men with mild to moderate erectile dysfunction of no clinically obvious organic cause. The study included two 28-day treatment periods, during which time sildenafil or placebo (25-75 mg, based on efficacy) was taken as required., Results: Compared with placebo, sildenafil was associated with increases in frequency of use, erections adequate for sexual intercourse and level of sexual satisfaction (P:<0.0001). More patients receiving sildenafil stated they would use the treatment again compared with those receiving placebo (P:<0.0001). There were no discontinuations due to sildenafil treatment., Conclusions: Sildenafil is effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause.

We set out to establish a simple, reproducible, rat in vitro model of erectile function and to use this to demonstrate the functional importance of both neuronal- and endothelial-derived nitric oxide within this animal. Two corpora cavernosal smooth muscle strips were harvested from sexually mature male Wistar rats and mounted in an organ bath for measurement of isometric tension. Following contraction with noradrenaline the strips were relaxed by the addition of either acetylcholine or sodium nitroprusside. Electrical field stimulation was performed in the presence of atropine and guanethidine. Relaxation responses were repeated in the presence of methylene blue, L-arginine, L-NNA and haemoglobin +/- L-arginine. Methylene blue abolishes the relaxation to acetylcholine and EFS; L-NNA and haemoglobin cause a significant impairment in the relaxation response. L-arginine reverses the effect of haemoglobin. In conclusion, the inhibitory, relaxant stimulus of rat corpora cavernosa is due to both neuronal nitric oxide and endothelial-derived nitric oxide released in response to cholinergic stimulation.

Audit data were collected continuously between February 1988 and July 1991. For the initial period (February 1988-June 1990) data were collected by monitoring of ward admission and discharge records and by collecting data from operating theatre records whilst complications were noted in a 'complications book' which was kept on the notes trolley. In July 1991, when a computerized system for storing and processing audit data was introduced into the department, the methods of data collection changed. For each patient a proforma was attached to the clinical notes which was filled in at each stage of the hospital stay. On this proforma was a list of possible complications which were ticked, as appropriate, at the time of discharge from hospital. We have reviewed the results of clinical audit during these two periods. The number of operations performed per month fell slightly in the latter period (p = 0.005). However, there was a significant increase in both the number of complications (p < 0.0001) and in the complication rate (p < 0.0001). Further analysis showed that there was a similar increase in the number of recorded major and minor complications, and that this increase was also seen even when changes in medical personnel were accounted for. We suggest that the increased complication rate recorded in the latter period reflects the change in the method of data collection. This has important implications when comparing outcome measures for clinical departments.

It has been reported that transurethral absorption of lignocaine may cause systemic toxicity when associated with mucosal damage within the urethra. We measured the serum levels of lignocaine in 30 patients after the transurethral administration of 400 mg lignocaine gel just before transurethral prostatectomy. In 11 patients additional lignocaine was given as part of the anaesthetic induction (Group A). In 19 patients no additional lignocaine was given (Group B). Two patients in Group A and three patients in Group B also underwent Otis urethrotomy. The mean peak plasma lignocaine concentration as measured by sequential venous samples was 1424 ng/ml in Group A and 72 ng/ml in Group B. We conclude that 400 mg lignocaine gel applied endourethrally before transurethral resection of the prostate results in plasma concentrations well below the toxic levels.