Dan Wood

Recreational ketamine: from pleasure to pain

Whats known on the subject? and What does the study add?

The cellular basis of contraction in human detrusor smooth muscle from patients with stable and unstable bladders

Studying the cellular physiology of human detrusor muscle obtained from patients with normally functioning bladders and comparing it with that of detrusor muscle from patients with unstable bladders may help identify potential targets for drug therapy in patients with abnormal bladder function. Considerable advances have been made in the understanding of the cellular processes that result in contraction and relaxation of detrusor smooth muscle, particularly in the role and modulation of calcium. Several changes in these cellular mechanisms that impair normal function have been observed in detrusor muscle from patients with unstable bladders. Whether these changes represent primary causes of bladder dysfunction or whether they are secondary to bladder dysfunction remains to be determined. Nevertheless, the identification of specific cellular lesions in bladder dysfunction presents a novel approach to identification of drug targets and potential treatment modalities.

Evaluation of Retained Testes in Adolescent Girls and Women with Complete Androgen Insensitivity Syndrome

PURPOSE To evaluate the magnetic resonance (MR) imaging appearance of the testes in women with complete androgen insensitivity syndrome (CAIS), including any benign or malignant changes. MATERIALS AND METHODS This was a retrospective review of the testicular MR images and histologic reports from 25 patients with CAIS who chose to retain their testes beyond age 16 years and who were imaged between January 2004 and December 2010. Ethical approval was obtained, and informed consent was obtained from each subject to review the medical records, images, and histologic slides and reports. Imaging and histologic findings were compared. RESULTS Twelve patients (mean age, 24 years; age range, 18-39 years) retained their testes and 13 (mean age, 22 years; age range, 17-37 years) eventually underwent gonadectomy. Review of the MR images showed that testicular parenchyma was heterogeneous in 30 of 46 testes (65%). The most common changes on MR images included simple-looking paratesticular cysts (34 of 46 testes, 74%) and low-signal-intensity, well-defined Sertoli cell adenomas (26 of 46 testes, 56%). Correlation of the histologic and MR imaging findings showed that MR imaging could correctly depict the presence or absence of Sertoli cell adenomas in 19 of 23 testes (83%). Paratesticular cysts were correctly detected in 22 of 23 testes (96%). Microscopic examination showed that the testes were composed of atrophic seminiferous tubules, whereas germ cells were found in 13 of 26 testes (50%). All paratesticular cysts were confirmed to be benign; however, a focus of intratubular germ cell neoplasia was found in a Sertoli cell adenoma. Premalignant foci were detected in three patients, two with intratubular germ cell neoplasia and one with sex cord tumor with annular tubules. No invasive cancers were found. CONCLUSION MR imaging is accurate in the detection of testicular changes, including paratesticular cysts and Sertoli cell adenomas. Although these changes are usually benign, Sertoli adenomas can sometimes harbor premalignant lesions. MR imaging cannot depict premalignant changes; therefore, the standard of care for patients with CAIS should remain gonadectomy after puberty.

Current status of tissue engineering in urology

Purpose of review Tissue engineering is a rapidly advancing technology that is shifting from the laboratory to urological practice. The review explores recent developments and considers the relationship to existing treatments. Recent findings Different strategies to generate transplantable tissue grafts in vitro and harness host regenerative processes for integration of grafts and biomaterials in vivo are common themes in the recent literature. Highlights include dynamic cell culture to precondition grafts and the use of omental wrapping to promote vascularization. Emphasis on specific cell culture conditions is set to shift towards the monitoring of differentiation and functional outcome. The future might encompass the use of stem cells to overcome the issues of harvesting cells from diseased tissues. Improved understandings of scaffold and cell interactions are particularly important to advance graft development and outcome. Recent trials give some indication of clinical outcome for tissue-engineered treatments, but patient benefit could be difficult to interpret in salvage cases. Summary Tissue engineering applications can be broken down into tissue- or organ-based approaches, only through examining these in clinical settings can potential success can be judged. Treatments must be appropriately evaluated for risk/benefit in comparison to existing treatments. This approach requires open and robust debate amongst clinicians and scientists.

Standing the test of time: the long-term results of urethroplasty

The principle indication for urethral surgery is stricture disease. There are a number of factors that influence the outcome of surgery including location of the stricture, stricture length, aetiology, previous surgery and selection of procedure. Outcomes for different techniques are summarised. The gold standard remains anastomotic urethroplasty, where appropriate, with patch urethroplasty or two-stage stage procedures for more complicated strictures especially the penile urethra.

Reproductive outcomes in women with classic bladder exstrophy: an observational cross-sectional study

OBJECTIVE We sought to examine the reproductive outcomes of 52 women with classical bladder exstrophy. STUDY DESIGN This was an observational study with cross-sectional and retrospective arms. RESULTS The average age of the sample was 33 years (range, 17-63). Of those who had tried, 19/38 (66%) had conceived. A total of 57 pregnancies (3 sets of twins) were reported for the 19 patients and resulted in 34/57 live births (56%), 21/57 miscarriages (35%), 1/57 (2%) termination, and 4/57 (7%) stillbirths or neonatal deaths. Four deliveries resulted in major complications including 1 transection of the ureter (4%), 1 fistula formation (4%), and 2 postpartum hemorrhages (8%). There were 2 admissions to intensive care, one for urinary sepsis and another for massive obstetric hemorrhage. CONCLUSION Fertility is impaired in women with bladder exstrophy. Pregnancy is high risk both for the mother and baby. Delivery should be at a tertiary referral obstetric unit with urology cover. In the majority of cases planned cesarean section is the most appropriate mode of delivery.

A TERTIARY EXPERIENCE OF VESICO-VAGINAL AND URETHRO-VAGINAL FISTULA REPAIR: FACTORS PREDICTING SUCCESS

To review the outcomes of all patients referred with vesico‐vaginal (V VF) and urethro‐vaginal (UVF) fistulae to a tertiary centre, and to investigate the patient, fistula and surgical factors relevant to success.

Examining long term outcomes of Bladder Exstrophy: A 20 year follow up.

To examine long‐term quality‐of‐life, urinary continence and sexual function outcomes in patients diagnosed with bladder exstrophy (BE).

Practice changes in childhood surgery for ambiguous genitalia

OBJECTIVE In 2001, this team published an observational study of the clinical outcomes of a cohort of adolescent girls born with ambiguous genitalia. The poor outcomes observed represented a major scientific challenge to the standard practice of childhood feminising genital surgery. That publication was one of several contributing to a call for change in surgical practice, which culminated in the publication of the Chicago Consensus Document in 2006. The aim of this current study was to repeat the same evaluation of clinical outcomes on a recent cohort of adolescent girls and compare the two cohorts to identify differences in adolescent outcomes which may indicate a change in paediatric surgical practice. METHODS This was an observational study of a current cohort of adolescent girls treated in childhood for ambiguous genitalia and referred to a specialist adolescent disorders of sex development (DSD) service for assessment. Data were collected on surgical history, genital examination findings and treatment recommendations for 30 consecutive adolescents over a 5-year period. Findings were compared with those of a similar cohort of adolescent girls published over a decade previously. RESULTS Clitoral surgery remained common (93% vs 100%, current cohort vs historical cohort). However, concomitant vaginoplasty was performed less frequently (80 vs 100% current vs historical). Vaginoplasty revision surgery was also less commonly required (65 vs 81%), although 24% of the recent cohort still required major revision surgery prior to intercourse. There was some improvement to the cosmetic outcomes as deemed by the surgical team using the same criteria as the previous report. CONCLUSIONS This study provides some slight evidence of recent practice change. There was a small reduction in the number of vaginoplasties performed in childhood and an improvement in vaginoplasty outcomes and cosmesis. However, there was no identifiable change in management of clitoromegaly and the numbers of clitoral reduction operations remained high. This is surprising given the clear evidence of a detrimental impact of surgery on clitoral sensation and sexual function.

Stabilization of Renal Deterioration Caused by Bladder Volume Dependent Obstruction

PURPOSE Previously published data from our unit show the detrimental effect of excessive bladder filling at normal pressure on renal function in chronically dilated renal units. Synchronous cystometry and dynamic renography identified a critical volume of filling that prevents upper tract drainage. In this followup study we determined whether maintaining bladder volume below this critical level would halt renal deterioration. MATERIALS AND METHODS Followup data were collected on 20 patients in the original study. All had progressive renal function deterioration for which no other cause was identified. Creatinine measured nearest to the time of the study renogram served as a baseline and subsequent values were used to monitor renal function. Data were analyzed by the paired Student t test. RESULTS Complete data were obtained on 14 patients with a mean age of 34.4 years (range 22 to 70). The mean glomerular filtration rate at entry to this part of the study was 42 ml per minute per 1.73 m(2) (range 18 to 69). Four patients had a neuropathic bladder, 4 had posterior urethral valves, 4 had bladder exstrophy, 1 had radiation cystitis, 1 had a solitary pelvic kidney and detrusor failure, 5 had a native bladder and 9 underwent cystoplasty. Drainage was via the native urethra and a Mitrofanoff channel in 7 cases each. Mean followup was 27 months (range 3 to 39). There was no significant difference in mean +/- SD creatinine at baseline vs latest followup (168 +/- 72 vs 185 +/- 90 micromol/l, p >0.05). CONCLUSIONS In patients with bladder volume dependent renal obstruction function can be stabilized by consistently maintaining bladder volume below the critical level.