Serotonin exerts a direct modulatory role on bladder afferent firing in mice.

KEY POINTS: Functional disorders (i.e. interstitial cystitis/painful bladder syndrome and irritable bowel syndrome) are associated with hyperexcitability of afferent nerves innervating the urinary tract and the bowel, respectively. Various non-5-HT3 receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5-HT. Whilst 5-HT3 receptors were not detected in mouse urothelium, 5-HT3 receptors expressed on bladder sensory neurons plays a role in bladder afferent excitability both under normal conditions and in a mouse model of chronic visceral hypersensitivity. These data suggest that the role 5-HT3 receptors play in bladder afferent signalling warrants further study as a potential therapeutic target for functional bladder disorders. ABSTRACT: Serotonin (5-HT) is an excitatory mediator that in the gastrointestinal (GI) tract plays a physiological role in gut-brain signalling and is dysregulated in functional GI disorders such as irritable bowel syndrome (IBS). Patients suffering from IBS frequently suffer from urological symptoms characteristic of interstitial cystitis/painful bladder syndrome, which manifests due to cross-sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5-HT in bladder afferent signalling and its role in colon-bladder neuronal crosstalk remain elusive. The aim of this study was to investigate the action of 5-HT on bladder afferent signalling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid-induced colitis. Bladder afferent activity was recorded directly using ex vivo afferent nerve recordings. Expression of 14 5-HT receptor subtypes, the serotonin transporter (SERT) and 5-HT-producing enzymes was determined in the urothelium using RT-PCR. Retrograde labelling of bladder-projecting dorsal root ganglion neurons was used to investigate expression of 5-HT3 receptors using single cell RT-PCR, while sensory neuronal and urothelial responses to 5-HT were determined by live cell calcium imaging. 5-HT elicited bladder afferent firing predominantly via 5-HT3 receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5-HT bioavailability. Granisetron, a 5-HT3 antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5-HT exerts a direct effect on bladder afferents to enhance signalling. 5-HT3 antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders.

Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials.

BACKGROUND: Motility-related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development. METHODS: Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility-related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration-response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model. KEY RESULTS: Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%. CONCLUSIONS & INFERENCES: Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility.

Coblation-assisted Lewis and MacKay operation (CobLAMO): new technique for tongue reduction in sleep apnoea surgery.

BACKGROUND: Obstructive sleep apnoea is a common condition that is unfortunately associated with a high rate of patient non-compliance regarding device use. Newer surgical interventions have focused on procedures at the palate level, using variants of palatoplasty and transpalatal advancement. However, the extent of tongue reduction surgery required remains controversial. The authors propose an in-between variant that combines midline glossectomy resection (with minimal mucosal sacrifice) and lateral coblation tongue channelling. METHOD: Four patients underwent a coblation-assisted Lewis and MacKay operation, which is a new technique for tongue reduction. This involved a midline glossectomy combined with lateral coblation channelling of the tongue, alone or as part of major airway reconstruction. Demographic, polysomnographic and quality of life questionnaire data were collected prospectively and analysed. RESULTS AND CONCLUSION: No significant complications were noted in the four patients. (Results of the post-surgical outcomes are presented in another paper.) The coblation-assisted Lewis and MacKay operation reduced the potential complications of aggressive tongue surgery. The contours of the tongue were maintained, but significant reduction was still achieved.

Where do AMU nurses perceive their educational needs? Results of the 20:10 project.

UNLABELLED: Our aim was to identify the perceived educational needs of nurses working in acute medicine to enable development of a training curriculum specifically for this staff group. METHODS: Post-graduate nurses from North Wales were invited to list 20 conditions and 10 skills for which they felt under prepared for their work in acute medicine. A workshop was then organized, attended by acute medicine nurses, medical colleagues and educationalists from two local universities to discuss initial data. RESULTS: Nurses identified particular needs for education around presenting symptoms with perceived deficits in knowledge or training. We found a heavy emphasis on respiratory and cardiac conditions. There was considerable overlap with frequent diagnostic categories from non-surgical hospital discharges and with priorities for training of junior doctors. Skills were often those traditionally associated with medical staff or care of patients with critical illnesses. CONCLUSION: The 20:10 project represents the first attempt to map educational needs of nursing staff on the Acute Medical Units of a large University Health Board using self-reported needs. The identified needs will support professional development, create incentives for recruitment and guide University postgraduate developments and commissioning.

TIPS versus peritoneovenous shunt in the treatment of medically intractable ascites: a prospective randomized trial.

OBJECTIVE: We undertook a prospective randomized clinical trial comparing TIPS to peritoneovenous (PV) shunts in the treatment of medically intractable ascites to establish relative efficacy and morbidity, and thereby superiority, between these shunts. METHODS: Thirty-two patients were prospectively randomized to undergo TIPS or peritoneovenous (Denver) shunts. All patients had failed medical therapy. RESULTS: After TIPS versus peritoneovenous shunts, median (mean +/- SD) duration of shunt patency was similar: 4.4 months (6 +/- 6.6 months) versus 4.0 months (5 +/- 4.6 months). Assisted shunt patency was longer after TIPS: 31.1 months (41 +/- 25.9 months) versus 13.1 months (19 +/- 17.3 months) (P < 0.01, Wilcoxon test). Ultimately, after TIPS 19% of patients had irreversible shunt occlusion versus 38% of patients after peritoneovenous shunts. Survival after TIPS was 28.7 months (41 +/- 28.7 months) versus 16.1 months (28 +/- 29.7 months) after peritoneovenous shunts. Control of ascites was achieved sooner after peritoneovenous shunts than after TIPS (73% vs. 46% after 1 month), but longer-term efficacy favored TIPS (eg, 85% vs. 40% at 3 years). CONCLUSION: TIPS and peritoneovenous shunts treat medically intractable ascites. Absence of ascites after either is uncommon. PV shunts control ascites sooner, although TIPS provides better long-term efficacy. After either shunt, numerous interventions are required to assist patency. Assisted shunt patency is better after TIPS. Treating medically refractory ascites with TIPS risks early shunt-related mortality for prospects of longer survival with ascites control. This study promotes the application of TIPS for medically intractable ascites if patients undergoing TIPS have prospects beyond short-term survival.

Pathways to fitness for practice: National Vocational Qualifications as a foundation of competence in nurse education.

Nurse education is currently undergoing major change. This article seeks to examine how National Vocational Qualifications (NVQs) are contributing to the future of nurse education. Criticisms of Project 2000 (P2K) include failure of the programme to produce nurses who are 'fit for practice' at the point of registration. A major criticism was that there is not enough skills-based training included. Following a recent report, recommendations were made which included a move to introduce a competence-based approach in nurse education. This approach is becoming more evident in both pre- and post-registration nurse education. A mapping exercise demonstrated that many of the UKCC competencies for pre-registration nurse education could be mapped to care NVQs. The article concludes that the positive aspects of care NVQs and P2K education should be embraced to enable programmes of nurse education to prepare nurses who are 'fit for practice'.

Interventional radiology placement of twin Tesio catheters for dialysis access: review of 75 patients.

PURPOSE: To evaluate the safety and efficacy of modern interventional radiology techniques and imaging guidance for placement of jugular vein twin Tesio hemodialysis catheters. MATERIALS AND METHODS: Eighty-two sets (75 patients) of twin Tesio catheters were percutaneously placed in the right (n = 70) and left (n = 12) internal jugular veins with use of ultrasound (US) and fluoroscopic guidance. Immediate procedural and late complications were recorded. The efficacy of the Tesio system was also evaluated. RESULTS: With US and fluoroscopic guidance, the technical success for access and catheter placement was 100%. Measured dialysis blood flow rate of greater than 375 mL/min was obtained in 95% of the patients and recirculation averaged 4.6% +/- 5%. An inadvertent common carotid artery puncture occurred in one (0.6%) patient and prolonged exit site bleeding occurred in another five patients (3%). Each of these was successfully controlled with compression. More chronically, catheter thrombosis and exit site infection occurred each at the rate of 0.16 episodes per 100 catheter days. All thrombosis and exit site infections responded to local thrombolysis and antibiotic therapy, respectively. Bacteremia occurred in 20 patients and required catheter removal in five patients. There was no clinical evidence of upper extremity or superior central vein thrombosis. CONCLUSION: Placement of internal jugular, twin Tesio catheters with use of imaging and interventional techniques provides a safe and efficacious means of either short or long-term hemodialysis.

The role of the midwife in perineal wound care following childbirth.

Midwives have an important role to play in the care of perineal wounds following childbirth. A wide variety of practices are carried out in this area. However, some current practices may not be beneficial to the promotion of wound healing. Midwives must realize the relevance of their care and potential impact, both positive and negative, of advocated treatments in wound healing. The maintenance of effective pain relief must be balanced with the need to promote wound healing. It is important that midwives recognize the need for research-based practice and that an audit is set up nationally to evaluate the efficacy of treatments and practice. Research, audit and evaluation of services are the central processes involved in providing effective and efficient care, as advocated by the Department of Health (1993).

Pneumocystis carinii pneumonia with an atypical granulomatous response.

Pneumonia due to Pneumocystis carinii may present atypical radiographic and pathologic findings. We report the case of a 32-year-old man with acquired immune deficiency syndrome (AIDS) whose chest roentgenogram showed a bilateral diffuse nodular pattern suggestive of miliary tuberculosis. Diagnosis ultimately required open lung biopsy, which showed evidence of an atypical granulomatous reaction with Pneumocystis carinii in the absence of other organisms. P carinii pneumonia must be considered in the differential diagnosis of patients with AIDS with nodular pulmonary densities and evidence of an atypical granulomatous reaction on pathologic specimens.