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Biomedical subjects

P D Wilson

Publications and source records attributed to P D Wilson.

At least 19 recordsLinked to original sources

Laparoscopic colposuspension for urinary incontinence in women.

BACKGROUND: Laparoscopic colposuspension was one of the first minimal access operations for the treatment of women with stress urinary incontinence, with the presumed advantages over traditional Burch colposuspension of avoiding major incisions, shorter hospital stay, and quicker return to normal activities. A variety of approaches and methods are used. OBJECTIVES: To determine the effects of laparoscopic colposuspension for urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 21 September 2005). Additional trials were sought from other sources such as reference lists, reviews and researchers and authors were contacted for unpublished data and trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptomatic or urodynamic diagnosis of stress or mixed incontinence that included laparoscopic surgery in at least one arm of the study. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers. Data were extracted by two of the reviewers and cross checked by another. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: Twenty-one eligible trials were identified. Nine involved the comparison of laparoscopic with open colposuspension. Whilst the women's subjective impression of cure seemed similar for both procedures in the short and medium term follow-up, there was some evidence of poorer results of laparoscopic colposuspension, within 18 months, on objective outcomes. Two poor quality trials reported conflicting long term results (after five years) for this comparison. No significant differences were observed for post-operative urgency, voiding dysfunction or de novo detrusor overactivity. Trends were shown towards a lower perioperative complication rate, longer operating time, less intraoperative blood loss, less postoperative pain, shorter hospital stay, quicker return to normal activities, and shorter duration of catheterisation for laparoscopic compared with open colposuspension. Benefits did not come without a price, as laparoscopic colposuspension in the short term is more costly.Eight studies compared laparoscopic colposuspension with newer 'self-fixing' vaginal slings. Overall there were no significant differences in the reported subjective cure rates of the two procedures, however vaginal sling procedures did have significantly higher objective cure rates at 18 months. No significant differences were observed for post-operative voiding dysfunction, de novo detrusor activity and perioperative complications. Laparoscopic colposuspension has a significantly longer operation time, longer hospital stay and slower return to normal activities when compared to the sling procedures. Significantly higher subjective and objective (dry on 'ultrashort' pad test) one year cure rates were found for women randomised to two paravaginal sutures compared with one suture in a single trial (89% versus 65% and 83% versus 58% respectively). Two small studies compared sutures with mesh and staples for laparoscopic colposuspension and the comparisons, although showing a trend towards favouring the sutures, were not significant. One study compared transperitoneal with extraperitoneal access for laparoscopic colposuspension but it was also small and of poor quality. AUTHORS' CONCLUSIONS: The long-term performance of laparoscopic colposuspension remains uncertain. Currently available evidence suggests that it may be as good as open colposuspension at two years post surgery. Like other laparoscopically performed operations, patients having laparoscopic colposuspension recovered quicker, but the operation itself took longer to perform. However, the newer vaginal sling procedures appear to offer even greater benefits of minimal access surgery and better objective outcomes in the short-term. If laparoscopic colposuspension is performed, two paravaginal sutures appear to be more effective than one. The place of laparoscopic colposuspension in clinical practice should become clearer when ongoing trials are reported and when there are more data available describing long-term cure results.

Female↗

New postnatal urinary incontinence: obstetric and other risk factors in primiparae.

OBJECTIVE: To identify obstetric and other risk factors for urinary incontinence that occurs during pregnancy or after childbirth. DESIGN: Questionnaire survey of women. SETTING: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). POPULATION: A total of 3405 primiparous women with singleton births delivered during 1 year. METHODS: Questionnaire responses and obstetric case note data were analysed using multivariate analysis to identify associations with urinary incontinence. MAIN OUTCOME MEASURES: Urinary incontinence at 3 months after delivery first starting in pregnancy or after birth. RESULTS: The prevalence of urinary incontinence was 29%. New incontinence first beginning after delivery was associated with older maternal age (oldest versus youngest group, OR 2.02, 95% CI 1.35-3.02) and method of delivery (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19-0.41). There were no significant associations with forceps delivery (OR 1.18, 95% CI 0.92-1.51) or vacuum delivery (OR 1.16, 95% CI 0.83-1.63). Incontinence first occurring during pregnancy and still present at 3 months was associated with higher maternal body mass index (BMI>25, OR 1.68, 95% CI 1.16-2.43) and heavier babies (birthweight in top quartile, OR 1.56, 95% CI 1.12-2.19). In these women, caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27-0.58) but incontinence was not associated with age. CONCLUSIONS: Women have less urinary incontinence after a first delivery by caesarean section whether or not that first starts during pregnancy. Older maternal age was associated with new postnatal incontinence, and higher BMI and heavier babies with incontinence first starting during pregnancy. The effect of further deliveries may modify these findings.

Adult↗

Childbirth and pelvic floor trauma.

The issue of traumatic damage to the pelvic floor in childbirth is attracting more and more attention amongst obstetric caregivers and laypersons alike. This is partly due to the fact that elective caesarean section as a potentially preventative intervention is increasingly available and perceived as safe. As there is a multitude of emotive issues involved, including health economics and the relative roles of healthcare providers, the discussion surrounding pelvic floor trauma in childbirth has not always been completely rational. However, after 25 years of urogynaecological research in this field it should be possible to determine whether pelvic floor trauma in childbirth is myth or reality, and, if real, whether it matters for the pathogenesis of incontinence and prolapse. On reviewing the available evidence, it appears that there are sufficient grounds to assume that vaginal delivery (or even the attempt at vaginal delivery) can cause damage to the pudendal nerve, the inferior aspects of the levator ani muscle and fascial pelvic organ supports. Risk factors for such damage have been defined and variously include operative vaginal delivery, a long second stage, and macrosomia. It is much less clear, however, whether such trauma is clinically relevant, and how important it is in the aetiology of pelvic floor morbidity later in life.

Cesarean Section↗

Laparoscopic colposuspension versus urethropexy: a case-control series.

Laparoscopic colposuspension (LC) was first described in the early 1990s as a technique distinct from open Burch colposuspension. Subsequently, however, LC was closely modelled along the lines of the Burch technique, and the distinct features of the original urethropexy (UP) were largely disregarded. In this case-control series the authors aimed to compare symptoms and anatomical outcomes after standard LC and urethropexy +/- paravaginal repair. The design was a clinical retrospective case-control trial. The setting was the urogynaecology and endogynaecology services of tertiary hospitals. Fifty patients after LC and 50 women after UP surgery, matched for age, body mass index, previous surgery, pre-existing urge incontinence and length of follow-up (1.01 year, range 0.02-3.54 years) for LC and 0.98 years (range 0.06-3.55 years) for UP). Intervention consisted of standardised interview and translabial ultrasound imaging. There were no significant differences for subjective cure of stress incontinence (80% for UP vs. 74% for LC), postoperative urge incontinence, frequency and nocturia. Significantly more UP patients complained of voiding dysfunction (p=0.01). Significant differences were found for urethral rotation, position of the bladder neck on Valsalva and bladder neck descent on Valsalva (all p<0.001). Both procedures were shown to be effective in curing stress incontinence. The incidence of bladder symptoms was comparable, with the exception of voiding difficulty. Significant differences were observed regarding anatomical appearances, with urethropexies showing more recurrent bladder neck hypermobility and cystocele.

Adult↗

TVT and Sparc suburethral slings: a case-control series.

Two midurethral slings, TVT and Sparc, are the subject of this case-control series aimed at assessing sling placement, voiding function, bladder symptoms and patient satisfaction. Thirty-seven Sparc and 69 TVT patients were matched for age, body weight, pre-existing urge incontinence, preoperative voiding, concomitant surgery and length of follow-up (mean 0.6, range 0.1-1.5 years). There were no significant differences for subjective cure/improvement, satisfaction or symptoms of incontinence. The clinical stress test was positive in 8/37 Sparc vs 4/69 TVT patients ( p=0.019). The TVT had a more negative effect ( p=0.001) on postoperative voiding. The Sparc was situated more cranially at rest and further from the symphysis pubis, and was more mobile ( p<0.001) on Valsalva. There are significant differences in medium-term outcomes after TVT and Sparc, affecting tape placement, mobility, effect on voiding function and objective stress continence. Patient satisfaction and subjective cure rates seem similar.

Case-Control Studies↗

The 'iris effect': how two-dimensional and three-dimensional ultrasound can help us understand anti-incontinence procedures.

OBJECTIVE: The objective of this prospective, observational study in patients after tension-free vaginal tape (TVT) implantation was to describe the spatial relationship between suburethral sling implants, urethra and bony pelvis with the help of translabial two-dimensional and three-dimensional (3D) ultrasound. METHODS: A total of 141 women were examined by translabial ultrasound, supine and after voiding. The TVT sling is highly echogenic and easily identified posterior to the urethra. Tape location was described in the mid-sagittal plane relative to bladder neck and inferoposterior symphyseal margin, at rest and on Valsalva maneuver. In a subset of 83 women, 3D volume ultrasound was performed. RESULTS: The cranial tape margin was situated on average 9.3 mm above and 16.5 mm posterior to the symphyseal margin (Valsalva: 3.9 mm below and 9.6 mm behind the symphysis); the average tape movement on Valsalva was 16 (range, 2-34.2) mm. The distance between tape and inferoposterior symphyseal margin narrowed highly significantly from 20.4 +/- 4.3 mm at rest to 12.9 +/- 3.9 mm on Valsalva (P < 0.001). When a fitted line plot was placed through tape coordinates on an x-y coordinate system, it became evident that tape movement occurs in an arc around the fulcrum of the posterior symphysis pubis. The result is an increasing reduction in the gap between tape and symphysis pubis (termed the 'iris effect'), implying mechanical compression of the urethra. CONCLUSIONS: The curative effect of the TVT on stress incontinence is likely to be due to mechanical compression of the urethra between implant and symphysis pubis. A large variation in tape location and movement explains its wide margin of clinical safety and efficacy.

Female↗

Age-dependent telomere attrition as a potential indicator of racial differences in renal growth patterns.

BACKGROUND: Racial differences in the predilection to salt sensitivity may arise from different renal growth patterns. To test this idea, we monitored age-dependent telomere attrition rate, reflecting largely the replicative history of somatic cells, in the outer renal cortex and the inner renal medulla of African Americans and Caucasians. METHODS: Telomere length, determined by the mean length of the terminal restriction fragments (TRF), was measured in specimens from 58 African-American and 63 Caucasian males, ages 1 day to 71 years. RESULTS: In the outer renal cortex, TRF length attrition rate was significantly slower in African Americans (-0.021 +/- 0.0064 kb/year) than in Caucasians (-0.060 +/- 0.0094 kb/year) (p = 0.0007). In both ethnic groups the TRF length attrition rate was slower in the inner medulla than in the outer renal cortex, but without significant racial differences. CONCLUSIONS: The proximal tubule is the most abundant nephron structure in the outer renal cortex. Less proliferative growth of proximal tubular cells in kidneys from African Americans may be one factor explaining the slower age-dependent telomere attrition rate in the outer renal cortex of African Americans than in Caucasians.

Adolescent↗

The day of discharge after total hip arthroplasty and the achievement of rehabilitation functional milestones: 11-year trends.

This is a report on 11 years (1990-2000) of total hip arthroplasty cases and days of discharge from one large city hospital. In 1990, patients stayed an average of 9.7 days after surgery. By 2000, patients stayed only 5.3 days. In general, women stayed longer than men, but this gap had nearly disappeared by 2000. The patients discharged in 2000 achieved fewer functional milestones during their hospital stay than those discharged in 1990.

Aged↗

Laparoscopic colposuspension for urinary incontinence in women.

BACKGROUND: Laparoscopic colposuspension is a relatively new operation for the treatment of women with stress urinary incontinence with the presumed advantages over traditional Burch colposuspension of avoiding major incisions, shorter hospital stay, and quicker return to normal activities. A variety of approaches and methods are used. OBJECTIVES: To determine the effects of laparoscopic colposuspension surgery on urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised register. The date of the most recent search was April 2001. Additional trials were sought from other sources such as reference lists, conference proceedings, reviews and unpublished research. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptomatic or urodynamic diagnosis of stress or mixed incontinence that included laparoscopic surgery in at least one arm of the study. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers. Data were extracted by two of the reviewers and cross checked by another. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: Eight eligible trials were identified. Five included 233 women receiving a laparoscopic and 254 women an open colposuspension. Whilst the women's subjective impression of cure seemed similar for both procedures up to 18 months there was some evidence of poorer results on objective outcomes. A single trial suggested poorer long-term performance, but this may reflect surgical inexperience of laparoscopic colposuspension. No significant differences were observed for post-operative urgency, voiding dysfunction or de novo detrusor instability. Trends were shown towards a higher complication rate, longer operating time, less intraoperative blood loss, less postoperative pain, shorter hospital stay, quicker return to normal activities, and shorter duration of catheterisation for laparoscopic compared with open colposuspension. Significantly higher subjective and objective (dry on 'ultrashort' pad test) one year cure rates were found for women randomised to two paravaginal sutures compared with one suture in a single trial (89% vs 65% and 83% vs 58% respectively). One study compared sutures with mesh and staples for laparoscopic colposuspension but it was too small to allow a reliable comparison. One study compared transperitoneal with extraperitoneal access for laparoscopic colposuspension but it was also small and of poor quality. REVIEWER'S CONCLUSIONS: The long-term performance of laparoscopic colposuspension is uncertain. Currently available evidence suggests that it may be poorer than open colposuspension. Like other laparoscopically performed operations, laparoscopic colposuspension leads to a quicker recovery, but takes longer to perform and may be associated with more surgical complications. If it is performed, two paravaginal sutures appear to be more effective than one. The place of laparoscopic colposuspension in clinical practice should become clearer when ongoing trials are reported and when there are more data available describing long-term cure results.

Female↗

The genes and proteins associated with poly-cystic kidney diseases.

Genetically based polycystic kidney diseases include autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases, nephronophthisis and medullary cystic disease. The PKD1 and PKD2 genes responsible for ADPKD and their respective encoded proteins polycystin-1 and polycystin-2 are under intense study and clues are developing as to their function and roles in the disease process. Structure-function analysis suggests that polycystins form multiprotein complexes with focal adhesion and cell-cell adherens junction proteins, which then initiate intracellular signaling events culminating in regulation of transcription of genes controlling proliferation and differentiation. Although less is known about the PKHD-encoded fibrocystin responsible for ARPKD or about the NPH1-encoded nephrocystin responsible for nephronophthisis, it is proposed that they function in the same cellular pathway involving protein-protein interactions, signal transduction and regulation of gene transcription. ADPKD epithelia are more adherent to collagen, less migratory, fail to recruit FAK to polycystin complexes and show aberrant, persistent expression of the fetal genes Erb-B2 and beta2 subunit of NaK-ATPase after birth. It is suggested that the function of the polycystin complex is to act as a key developmental regulator of renal tubule morphogenesis.

DNA Mutational Analysis↗

Conservative management of persistent postnatal urinary and faecal incontinence: randomised controlled trial.

OBJECTIVES: To assess the effect of nurse assessment with reinforcement of pelvic floor muscle training exercises and bladder training compared with standard management among women with persistent incontinence three months postnatally. DESIGN: Randomised controlled trial with nine months' follow up. SETTING: Community intervention in three centres (Dunedin, New Zealand; Birmingham; Aberdeen). PARTICIPANTS: 747 women with urinary incontinence three months postnatally, allocated at random to intervention (371) or control (376) groups. INTERVENTION: Assessment by nurses of urinary incontinence with conservative advice on pelvic floor exercises at five, seven, and nine months after delivery supplemented with bladder training if appropriate at seven and nine months. MAIN OUTCOME MEASURES: Primary: persistence and severity of urinary incontinence 12 months after delivery. Secondary: performance of pelvic floor exercises, change in coexisting faecal incontinence, wellbeing, anxiety, and depression. RESULTS: Women in the intervention group had significantly less urinary incontinence: 167/279 (59.9%) v 169/245 (69.0%), difference 9.1% (95% confidence interval 1.0% to 17.3%, P=0.037) for any incontinence and 55/279 (19.7%) v 78/245 (31.8%), difference 12.1% (4.7% to 19.6%, P=0.002) for severe incontinence. Faecal incontinence was also less common: 12/273 (4.4%) v 25/237 (10.5%), difference 6.1% (1.6% to 10.8%, P=0.012). At 12 months women in the intervention group were more likely to be performing pelvic floor exercises (218/278 (79%) v 118/244 (48%), P<0.001). CONCLUSIONS: A third of women may have some urinary incontinence three months after childbirth. Conservative management provided by nurses seems to reduce the likelihood of urinary and coexisting faecal incontinence persisting 12 months postpartum. Further trials for faecal incontinence are needed.

Adult↗

Atrioventricular septal defects: possible etiologic differences between complete and partial defects.

BACKGROUND: Recent advances in clinical, pathological, and genetic aspects of atrioventricular septal defects (AVSD) have set the stage for epidemiologic investigations into possible risk factors. Previous analyses of the total case group of AVSD included complete and partial subtypes without analysis of the subsets. METHODS: To address the question of possible morphogenetic heterogeneity of AVSD, the Baltimore-Washington Infant Study data on live-born cases and controls (1981-1989) was reanalyzed for potential environmental and genetic risk-factor associations in complete AVSD (n = 213), with separate comparisons to the atrial (n = 75) and the ventricular (n = 32) forms of partial AVSD. RESULTS: Complete and ventricular forms of AVSD had a similar proportion of isolated cases (12.2% and 15.6%, respectively, without associated extracardiac anomalies) and high rates of Down syndrome, whereas the atrial form of partial AVSD included 55% isolated cases. Trisomy 18 occurred in 22% of infants with the ventricular form, compared with <2% in the other AVSD groups. Analysis of potential risk factors revealed further distinctions. Complete AVSD as an isolated cardiac defect was strongly associated with maternal diabetes (odds ratio [OR] = 20.6; 95% confidence interval [CI] =5.6-76.4) and also with antitussive use (OR = 8.8; CI = 1.2-48.2); there were no strong associations other than maternal age among Down syndrome infants with this type of heart defect. Isolated cases with the atrial type of partial AVSD were associated with a family history of heart defects (OR = 6.2; CI = 1.4-24.4) and with paternal occupational exposures to ionizing radiation (OR = 5.1; CI = 1.4-27.4), but no risk factors were associated with Down syndrome. There were no significant associations of any risk factors in the numerically small subsets of isolated and Down syndrome cases with the ventricular form of partial AVSD. CONCLUSIONS: These results indicate a similar risk profile of complete AVSD and the ventricular type of partial AVSD, with a possible subset of the latter due to trisomy 18. Maternal diabetes constituted a potentially preventable risk factor for the most severe, complete form of AVSD.

Adult↗

Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants.

BACKGROUND: Intensive medical care of women with diabetes has reduced their risks of bearing infants with congenital anomalies. To assess the preventive potential of preconceptional care, the data of a population-based study of cardiovascular malformations (CVM) were analyzed to determine the morphogenetic specificity of maternal diabetes risks, the morbidity and mortality of the infants, and maternal characteristics that might affect these risks. METHODS: The Baltimore-Washington Infant Study was a case-control study (1981-1989) that included all live born infants with confirmed CVM; control infants were a representative sample of the birth cohort. A questionnaire administered in home visits recorded parental information on social, medical, occupational, and environmental factors. For these analyses of preconceptional diabetes risks, the case group excluded chromosomal and mendelian disorders and was divided into 3 developmental categories and 12 diagnostic groups. RESULTS: Preconceptional maternal diabetes was strongly associated with CVM of early embryonic origin (odds ratio [OR] = 4.7, 95% confidence interval [CI] 2.8-7.9) and with cardiomyopathy (OR = 15.1, 95% CI 5.5-41.3), but not with obstructive and shunting defects (OR = 1.4, 95% CI 0.7-3.0). There was heterogeneity within these developmental categories: among laterality defects, diabetes was associated only with cardiovisceral and atrioventricular discordance (OR = 10.0, 95% CI 3.7-27.0); among outflow tract anomalies, the risk was strongly associated with normally related great arteries (OR = 6.6, 95% CI 3.2-13.3) but not with simple transpositions; and among atrioventricular septal defects, diabetes was associated with the complete but not with the partial forms (OR = 22.8, 95% CI 7.4-70.5). The association in early CVM was strongest among infants with multisystem, predominantly VACTERL, anomalies. All-cause mortality of infants with CVM was 39% among those with diabetic mothers and 17.8% in those with nondiabetic mothers. Deceased infants of diabetic mothers were also more likely to have extracardiac anomalies (P = 0.041), to be born prematurely (P = 0.007), and to have low birth weight (P = 0.011). Multivariate analyses of maternal factors revealed no significant confounders of the diabetes associations. CONCLUSIONS: The evidence of diabetes-induced major cardiac defects is of urgent clinical significance. The effectiveness of early preconceptional care in the prevention of congenital anomalies has been demonstrated repeatedly.

Adult↗

Irritative symptoms after colposuspension: are they due to distortion or overelevation of the anterior vaginal wall and trigone?

Symptoms of bladder irritability are common after incontinence surgery but their cause is unknown. This study tests the hypothesis that irritative symptoms after colposuspension are due to distortion of the trigone. As part of longitudinal follow-up studies, 175 women were examined 6 months to 12 years after either an open or a laparoscopic Burch colposuspension. The main outcome measures were symptoms of bladder irritability (frequency, nocturia and urge incontinence) and ultrasound findings (bladder neck position at rest and on Valsalva, the presence of a colposuspension ridge, ridge depth and ridge distance, and trigonal angle). Two positive associations between ultrasound parameters and symptoms of bladder irritability were observed: urge incontinence was more likely in the presence of bladder neck funneling, and women with nocturia had a higher trigonal angle. Increased distortion of the trigone was associated with a reduced incidence of urge incontinence in the subgroup of patients after laparoscopic colposuspension. The data presented in this study do not support the hypothesis that symptoms of bladder irritability are due to trigonal distortion or overelevation.

Colposcopy↗

The use of perineal ultrasound to quantify levator activity and teach pelvic floor muscle exercises.

Perineal ultrasound was used to detect and quantify levator activity by measuring the displacement of the internal urethral meatus against the inferoposterior margin of the symphysis pubis. Women who had previously been instructed in pelvic floor muscle exercises were more likely to contract the levator muscle when asked to do so than were those without previous instruction (P<0.0001). Of the 56 women who were unable to contract the pelvic floor on request, 32 (57%) eventually succeeded with visual ultrasound biofeedback. Pelvic floor muscle assessment and teaching can be used as an adjunct to the ultrasound assessment of urogynecologic patients, requiring at most 5 minutes. It allows quantification of lavator activity and can provide visual biofeedback, which is easily understood and readily accepted by women.

Adult↗

Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort.

To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.

Adult↗

Obstetric practice and faecal incontinence three months after delivery.

OBJECTIVE: To determine whether obstetric and maternal factors relate to faecal incontinence at three months postpartum. SETTING: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). POPULATION: All women who delivered during one year in the three maternity units. METHODS: Postal questionnaire at three months postpartum, to obtain information on faecal incontinence, linked to obstetric casenote data. MAIN OUTCOME MEASURES: Prevalence of faecal incontinence. RESULTS: 7879 questionnaires were returned, a 71.7% response rate. The prevalence of faecal incontinence was 9.6%, with 4.2% reporting this more often than rarely. Logistic regression, confined to primiparae, showed that forceps delivery was a predictor of an increased risk of symptoms (OR = 1.94, 95% CI 1.30 to 2.89) while vacuum extraction was not associated. Caesarean section was marginally associated with a reduced risk (OR = 0.58, 95% CI 0.35 to 0.97). Older maternal age, Indian sub-continent ethnic origin and body mass index 'not known' also showed significant associations. No associations were found for induced labour, duration of second stage labour, episiotomy, laceration or birthweight. CONCLUSIONS: Women delivered by forceps had almost twice the risk of developing faecal incontinence, whereas vacuum extraction was not associated with faecal incontinence at three months postpartum. Caesarean section appears to offer some protection.

Adult↗

Expression of the urate transporter/channel is developmentally regulated in human kidneys.

Recombinant protein prepared from cDNA cloned from rat kidney and its human homolog function as urate transporter/channels in lipid bilayers. Using the antibody (anti-uricase) that detected the rat cDNA clone, we now demonstrate that normal human kidneys contain an immunoreactive protein of identical size to that in rat kidney (36-37 kDa), presumably the human urate transporter/channel (hUAT). The amount of hUAT in kidney homogenates increases progressively from 13 wk of gestation to the early postnatal period. During gestation, hUAT expression is confined to the cytoplasm of proximal tubules of Stage III and/or IV nephrons. However, at 1 yr of age hUAT is primarily located subapically and within brush borders of proximal tubules. Xenopus laevis oocytes and differentiated A6 cells injected with cRNA and transfected with cDNA of hUAT, respectively, demonstrated a similar pattern: hUAT is not detected in oocytes but is abundantly expressed in cytoplasm and plasma membranes of A6 cells. These data imply that different developmental factors regulate the initiation of cytoplasmic hUAT expression and subsequent insertion into human proximal tubule brush-border membranes.

Adolescent↗