Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.
Using the VKD resulted in significant early improvement in SUI scores, and pelvic muscle strength had improved significantly by the end of the study. The VKD proved useful as an adjunct for pelvic floor training.
As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team-based approach to treatment planning and care, delivery of best-practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.
Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of “much/very much improved” (CGI-SF score = 2) was reported by 58.3% (n = 21/36) of bupropion SR-assigned versus 27.7% (n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.
Hypogonadism is a medical condition characterised by testosterone deficiency in males, accompanied by numerous clinical symptoms, which can negatively affect quality of life and multiple organ systems. Late-onset hypogonadism describes testosterone deficiency or reduced effect seen in ageing men. The conditions are generally managed using testosterone supplementation. Many formulations of testosterone are available, including deep-muscle injections, buccal formulations, transdermal patches and topical gels. Testim gel 1% testosterone gel (Auxilium Pharmaceuticals, Inc. and Ipsen) has been shown to restore serum testosterone concentrations to within the normal range in men with hypogonadism. Two randomised, controlled studies showed that Testim gel significantly improved sexual motivation, desire, performance and function, as well as positive and negative mood scores and body composition after 90 days, compared with baseline. The magnitude of improvement seen with Testim gel was similar to that achieved with testosterone patches, but with fewer application-site reactions. In another study, improvements in mood and sexual function were seen within the first 2 weeks of treatment. Long-term, open-label extension studies of Testim gel suggest that clinical benefits are maintained for< or = 12 months without an additional increase in side effects. Notably, Testim gel treatment for 12 months was associated with a gradual increase in bone mineral density, suggesting that Testim gel may help to prevent osteoporosis. The most common adverse events associated with Testim gel were application-site reactions, increased haematological parameters, and moderately increased prostate-specific antigen levels that remained within the normal range in 96% of subjects. Men on any testosterone therapy will require careful monitoring, including serial digital rectal examination and prostate-specific antigen testing. Overall, the clinical evidence so far indicates that Testim gel is a safe and effective treatment option for daily use in the management of male hypogonadism.
OBJECTIVE To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice. PATIENTS AND METHODS Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan‐Meier method and multivariate analysis with Cox regression model. RESULTS In all, 358 patients had pcRPLND between September 1992 and April 2006, by one surgeon. In 48 patients the tumour markers were elevated at the time of surgery, they were on a ‘rising trend’ in 26 (54%) and ‘downward or stable’ trend in 22 (46%). The overall incidence of active germ cell tumour, differentiated teratoma and necrosis in the resected specimens was 58%, 25% and 17%, respectively. The median follow‐up was 51.5 months and the overall 5‐year survival was 69%. The favourable prognostic factors assessed by univariate analysis were elevation of α‐fetoprotein alone, complete resection of residual disease, histological finding of differentiated teratoma in the resected tissues and normalization of tumour markers after pcRPLND. By multivariate analysis the only statistically significant independent survival factor was the normalization of the tumour markers after pcRPLND. CONCLUSION For selected patients with elevated tumour markers after chemotherapy, RPLND can offer a significant chance of cure with no need for further chemotherapy. The patients most likely to benefit are those with elevations of α‐fetoprotein alone. In this group, pcRPLND can offer the prospect of long‐term survival and should be considered in the management of selected patients.
ObjectiveTo examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle‐income country.MethodsSix key sections were chosen: (1) high‐risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration‐naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast‐targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real‐world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes.ResultsMost voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high‐cost drugs in castration‐naïve or castration‐resistant metastatic prostate cancer in real‐world settings. All panellists recommended using generic drugs when available.ConclusionsThe MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle‐income country in a real‐world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.
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