Enhanced purinergic contractile responses and P2X1 receptor expression in detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.

Bladders from patients with detrusor overactivity have an increased atropine-resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia-glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia-glucopenia and reoxygenation result in increased atropine-resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37°C aerated with 21% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO2. Atropine-resistant contractile responses increased by 40.5 ± 7.3% after four cycles of hypoxia-glucopenia (10 min) and reoxygenation (1 h), whereas α,ß-methylene ATP-resistant responses did not increase. Expression of P2X1 receptors in the bladder was increased after hypoxia-glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor-mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia-glucopenia and reoxygenation cycling, because a non-specific P2X antagonist blocked most of the augmented response, whereas a P2X1-specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. In conclusion, four cycles of hypoxia-glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X1 receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic-mediated contractions.

Childbirth after pelvic floor surgery: analysis of Hospital Episode Statistics in England, 2002-2008.

OBJECTIVE: To report the numbers of patients having childbirth after pelvic floor surgery in England. DESIGN: Retrospective analysis of Hospital Episode Statistics data. SETTING: Hospital Episode Statistics database. POPULATION: Women, aged 20-44 years, undergoing childbirth after pelvic floor surgery between the years 2002 and 2008. METHODS: Analysis of the Hospital Episode Statistics database using Office of Population, Censuses and Surveys: Classification of Interventions and Procedures, 4th Revision (OPCS-4) code at the four-character level for pelvic floor surgery and delivery, in women aged 20-44 years, between the years 2002 and 2008. MAIN OUTCOME MEASURES: Numbers of women having delivery episodes after previous pelvic floor surgery, and numbers having further pelvic floor surgery after delivery. RESULTS: Six hundred and three women had a delivery episode after previous pelvic floor surgery in the time period 2002-2008. In this group of 603 women, 42 had a further pelvic floor surgery episode following delivery in the same time period. The incidence of repeat surgery episode following delivery was higher in the group delivered vaginally than in those delivered by caesarean (13.6 versus 4.4%; odds ratio, 3.38; 95% confidence interval, 1.87-6.10). CONCLUSIONS: There were 603 women having childbirth after pelvic floor surgery in the time period 2002-2008. The incidence of further pelvic floor surgery after childbirth was lower after caesarean delivery than after vaginal delivery, and this may indicate a protective effect of abdominal delivery.

Validation of the Patient Global Impression scales for use in detrusor overactivity: secondary analysis of the RELAX study.

OBJECTIVE: To assess construct validity of the Patient Global Impression scales (Severity [PGI-S], Bother [PGI-B] and Improvement [PGI-I]) for symptoms of detrusor overactivity (DO). DESIGN: Secondary analysis of a randomised trial of onabotulinum toxin A. SETTING: Eight UK urogynaecology departments. POPULATION: A total of 240 women with DO refractory to medical treatment randomised to receive 200 iu onabotulinum toxin A or placebo in the RELAX trial and followed up for 6 months. MAIN OUTCOME MEASURES: Urinary diaries and disease-specific quality of life (QoL) questionnaires were completed at baseline and during follow up. Discriminatory ability of the PGI-S, PGI-B and PGI-I scales to identify symptom severity and change in severity was assessed by comparing mean diary and QoL outcomes across the response categories, analysed by one-way analysis of variance. RESULTS: Data were available from 237 women (98.8%) for validation of PGI-S and PGI-B at baseline, and 192 women (80%) at 6 weeks follow up for validation of PGI-I. Leakage episodes (P = 0.01), urgency episodes (P = 0.019), urgency severity (P = 0.012), and QoL scores (all P < 0.001) were greater in women with more severe problems on PGI-S. Similar results were seen for PGI-B: leakage (P = 0.051), urgency episodes (P < 0.001), urgency severity (P < 0.001), and QoL scores (all P < 0.001). PGI-I responses demonstrated significant relationships with size of change of all variables (P < 0.001). The generic instrument EQ-5D had weaker relationships (PGI-S, P = 0.09; PGI-B, P = 0.004; PGI-I, P = 0.06), suggesting that it was less sensitive. CONCLUSIONS: The PGI scales are robust and valid instruments to assess disease severity, bother and improvement after treatment in women with detrusor overactivity.

Classification of episiotomy: towards a standardisation of terminology.

Seven episiotomy incisions are described in the literature, although only midline, mediolateral or lateral episiotomies are commonly used. Recent research has demonstrated variations in both site and direction of the incision, and differences between the angle of incision at the time of crowning of the fetal head and the angle of the scar once the wound has been repaired. We review this evidence and suggest that this variation may undermine the reliability of much published work. We suggest a standardised definition of each type of episiotomy to establish uniformity going forward, so that future studies are amenable to comparison and meta-analysis.

Colposuspension or TVT with anterior repair for urinary incontinence and prolapse: results of and lessons from a pilot randomised patient-preference study (CARPET 1).

In a multicentre randomised, unblinded patient preference pilot trial to assess the feasibility of a definitive randomised trial comparing colposuspension with tension-free vaginal tape (TVT) plus anterior repair in women with incontinence and prolapse, we found that 31 of 56 eligible women agreed to participate (55%). Recruitment was more successful face to face (87%) than by letter (16%). Only four of our women agreed to be randomised, 21 (68%) chose anterior repair+TVT and six (19%) chose colposuspension. This study demonstrates the importance of pilot work for complex trials to identify issues likely to adversely affect recruitment.

A urinary control device for management of female stress incontinence.

OBJECTIVE: To examine the performance of a silicon urinary control device for nonsurgical management of women with genuine stress incontinence. METHODS: A 3-month prospective study involved 41 women with genuine stress incontinence. They completed urinary diaries of voiding, incontinence, and severity of incontinence on a 4-point scale over a week. Subjects were taught how to apply the device and used it as required from the second week. Visual analogue scales were used to record aspects of use (such as acceptability, comfort, and ease of application), and 2-hour perineal pad tests were completed at recruitment, after 2 weeks, and after 3 months. Data were compared by Mann-Whitney U test, or Wilcoxon test. RESULTS: Ten women (24.4%) declined to participate and six (14.6%) withdrew before 2 weeks. Ten (24.4%) failed to attend for 2-week follow-up and 11 (26.8%) did not continue for 3 months. Two (4.9%) did not attend 3-month follow-up. Only two women (4.9%) completed the study. There was no difference in pad test results or in results from voiding diaries. CONCLUSION: The urinary incontinence device had low acceptability and was ineffective, and we cannot recommend it for nonsurgical management of genuine stress incontinence.

Evaluation of reagent strips in detecting asymptomatic bacteriuria in early pregnancy: prospective case series.

OBJECTIVE: To evaluate the performance of reagent test strips in screening pregnant women for asymptomatic bacteriuria at their first visit to an antenatal clinic. DESIGN: Prospective case series. SETTING: Antenatal clinic of a large inner city maternity hospital. SUBJECTS: All women attending for their first antenatal clinic. Patients taking antibiotics for any reason and those with urinary tract symptoms were excluded. INTERVENTION: A midstream urine specimen was divided; half was sent for microscopy and formal bacteriological culture and the other half was tested with a commercial reagent strip test for the presence of blood, protein, nitrite, and leucocyte esterase. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the reagent strips in diagnosing asymptomatic bacteriuria (defined as 10(5) colony forming units/ml urine). RESULTS: Sensitivity was low, with a maximum of 33% when all four tests were used in combination. Specificity was high, with typical values of 99% or more. Positive predictive value reached a maximum of 69% and negative predictive value was typically 95% or more. CONCLUSION: Urine reagent strips are not sufficiently sensitive to be of use in the screening for asymptomatic bacteriuria and therefore many patients would be missed. In view of the potentially serious sequelae of this condition in pregnant women we recommend that formal bacteriological investigation remain the investigation of choice in this group of patients.

Continence nurse treatment of women's urinary symptoms.

The aim of this study was to establish how accurately a trained continence nurse could allocate appropriate second-line conservative treatment to women without urodynamic investigations. Depending on the number of patients coming taking up the service, there were between five and 12 nurses operating at any one time. Women aged 40 years and over, of which there were 2421 reporting lover urinary tract symptoms, were randomly allocated to a new nurse-led continence service. Of these women, 450 subsequently underwent urodynamic investigation, before which the nurses documented which second-line conservative treatment would be appropriate. The results showed that of all women with detrusor overactivity, 79.1% were correctly allocated anticholinergic treatment, and 64.8% were allocated pelvic floor exercises (PFE). Of all women with urodynamic stress incontinence, 88.8% were allocated only one treatment. This study showed that a trained continence nurse is able to allocate conservative treatment appropriately to the majority of women without the need for urodynamic investigation. This indicated that the management of urinary dysfunction by a team of trained, dedicated nurses has the potential to reduce waiting lists for urodynamic investigation, avoid unnecessary investigations and achieve greater patient satisfaction.

Important clinical outcomes in urogynecology: views of patients, nurses and medical staff.

We attempted to grade treatment outcomes in female urinary incontinence by the perceived importance of these outcomes for patients, nursing staff and medical staff. One hundred millimeter visual analog scales (VAS) quantifying the relative importance of five clinical outcomes were sent to 100 patients, 50 nursing staff and 135 medical staff involved in continence care and median VAS scores for each outcome were compared between groups. Subjective improvement and improvement in quality of life were rated most highly. Median scores for subjective cure were 93 (76-99) for nurses, 93 (11-100) for patients and 91 (50-100) for ICS (UK) members. Median quality of life improvement scores were 92 (67-100), 93 (3-100) and 93 (74-100), respectively (not significant). There was a striking concordance of opinion regarding the importance of subjective improvement and improvement in quality of life. We suggest that these should become primary outcome measures in all future clinical trials and audits of incontinence treatments.

Treatment of hyperemesis gravidarum with the 5-HT3 antagonist ondansetron (Zofran).

Ondansetron is a 5-hydroxytryptamine receptor antagonist which is known to be a highly effective anti-emetic drug for chemotherapy-associated nausea and vomiting and for postoperative nausea. We report here a case where ondansetron was used in severe hyperemesis gravidarum to avoid parenteral nutrition. The drug was used intermittently in every trimester with no apparent adverse effects on mother or infant.

Second trimester fetal abnormality scans: do women know the reasons why they are done?

A 10 point questionnaire was given to 239 women attending for second trimester fetal abnormality ultrasound scans to explore their level of knowledge about the nature, purpose and limitations of the procedure. Questions were included about the conditions which could or could not be diagnosed, and about the accuracy and sensitivity of the procedure. Demographic data was also recorded. Two hundred and thirty-five forms were correctly completed. The percentage of women returning correct answers ranged from 58.8% to 100% and response rate was correlated with years of full time education in some questions. The results suggest that patients perceive the scan as a chance to see their baby and that many do not fully appreciate either the purpose or the limitations of fetal anomaly scanning. This may complicate the post-test counselling required if an abnormality is detected.

The Larsson frequency/volume chart is not a substitute for cystometry in the investigation of women with urinary incontinence.

The aim of the study was to assess the ability of the Larsson chart nomogram to predict the presence of detrusor instability or genuine stress incontinence without recourse to cystometry. The Larsson chart provides a probability of detrusor instability by plotting 24-hour urinary frequency against the range of void volumes. Frequency/volume chart data were obtained from the records of 216 patients who had undergone subtraction cystometry. The Larsson chart was assessed by comparing the probability of detrusor instability or of genuine stress incontinence obtained with the cystometric diagnosis. The maximum sensitivity of the Larsson chart was 52%, with a specificity of 70% for detrusor instability. For genuine stress incontinence these figures were 66% and 65% respectively. The Larsson chart provides no diagnostic information and does not remove the need for formal cystometric evaluation of patients with urinary incontinence.

The use of salivary stimulant pastilles to improve compliance in women taking oxybutynin hydrochloride for detrusor instability: a pilot study.

OBJECTIVE: To assess the efficacy of salivary stimulant pastilles in improving tolerance of and compliance with oxybutynin chloride for detrusor instability. PATIENTS AND METHODS: Thirty women with detrusor instability were treated with oxybutynin in either a fixed or variable dose. After 3 weeks, patients were given salivary stimulant pastilles (Salivix, Thames Laboratories, Clwyd, UK) to chew as often as required. Symptom diaries were used to record episodes of dry mouth (xerostomia) together with a 100 mm visual analogue scale (VAS) score of the severity of xerostomia. RESULTS: The frequency of xerostomia was unchanged but there was a significant decrease in median severity from 71 to 39 on the VAS (P < 0.05, Mann-Whitney U-test). Nine patients on the variable-dose regimen tolerated a higher dose of oxybutynin when taking the pastilles (P < 0.01, Wilcoxon's matched-pairs test). CONCLUSION: Salivary stimulant pastilles appear to be a useful adjuvant therapy for patients receiving oxybutynin chloride for detrusor instability, allowing higher doses of oxybutynin to be tolerated.

Preliminary experience with a urinary control device in the management of women with genuine stress incontinence.

OBJECTIVE: To evaluate the efficacy and acceptability of the FemAssist urinary control device (Insight Medical UK Ltd). PATIENTS AND METHODS: Twenty-seven women with cystometrically confirmed genuine stress incontinence performed a perineal 1 h pad-test; the pad test was then repeated with the FemAssist device in place and the difference in pad weights compared with and without the device in place. Patients were given 100 mm visual analogue scales (VAS) to measure discomfort, acceptability and embarrassment associated with using the device. RESULTS: The median (range) loss with and without the FemAssist device was 4.9 (0-65) mL and 21 (1-94), respectively (P < 0.01); 20 patients were less wet when using the device. The median (range) VAS scores were; discomfort 35 (4-93), embarrassment 11 (0-75), and acceptability 65 (3-100). Discomfort was greater among the women with a greater loss. The acceptability correlated negatively with discomfort (r = -0.53) and negatively with embarrassment (r = -0.39); 15 patients (56%) reported that they would use the device in the long-term. CONCLUSION: The FemAssist device produced a significant reduction in urine loss. The magnitude of benefit could not be predicted for an individual and the device was ineffective in some women. The use of the device was influenced by discomfort and associated embarrassment. The device has a role in the management of stress incontinence but patients must be assessed individually for suitability.

Preliminary investigations on androgen receptor gene mutations in infertile men.

A total of 50 men were selected from all patients attending an infertility clinic on the basis of oligozoospermia or azoospermia with concentrations of luteinizing hormone >6 IU/l and testosterone >30 nmol/l. Six of these men responded to written invitation and DNA was extracted from blood leukocytes. Individual exons of the androgen receptor gene were amplified by polymerase chain reaction and screened for the presence of mutations by denaturing gradient gel electrophoresis. The glutamine rich portion of exon 1 was sequenced directly. All of the coding sequence of the gene was examined except the glycine rich portion of exon 1 in all patients. No mutations or deletions were identified. Androgen receptor gene mutations do not appear to be present in infertile men with biochemical disturbances compatible with androgen resistance. It is therefore unlikely that such mutations are a major factor in the pathogenesis of oligozoospermia/azoospermia and infertility.

Computerised antenatal fetal heart rate recordings between 24 and 28 weeks of gestation.

OBJECTIVE: To assess computerised fetal heart rate recordings between 24 and 28 weeks of gestation for gestation related differences. DESIGN: Prospective, cross sectional observational study. SETTING: Liverpool Women's Hospital. POPULATION: 112 women: 28 at 27 weeks, 30 at 26 weeks, 27 at 25 weeks and 27 at 24 weeks of gestation, respectively. METHODS: Fetal heart recordings of 60 minutes duration were performed once in each pregnancy using the System 8000 fetal heart rate programme (System 8000, Oxford Sonicaid Ltd, Chichester, UK). For each gestational age, records were analysed for short term variation, basal heart rate, accelerations and time spent in high episodes. RESULTS: The mean short term variation increased with gestation (P = 0.05). No record had a short term variation <4 msecs. There was no relationship between heart rate and increasing gestation. The mean number of accelerations per record increased with increasing gestation (P < 0.01). 20% of recordings showed no accelerations > 15 bpm. The mean duration spent in episodes of high variation increased with gestation (P = 0.05). 13% of recordings showed no time spent in high episodes. All fetuses had normal outcomes at delivery. CONCLUSIONS: Absence of episodes of high variation or absence of accelerations is not an abnormal finding at lower gestations. The standard threshold of 4 msecs for short term variation appears to remain valid at lower gestations. These differences should be considered when using computerised CTG analysis at early gestations.