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Biomedical subjects

C O'Herlihy

Publications and source records attributed to C O'Herlihy.

At least 19 recordsLinked to original sources

Cells with haematopoietic stem cell phenotype in adult human endometrium: relevance to infertility?

BACKGROUND: Uterine lymphoid cell repertoires are specialized in order to meet the twin demands of successful pregnancy and local immunosurveillance. The possibility that some of these populations might differentiate locally from progenitor cells has been proposed. METHODS: Endometrial tissue from women with a history of infertility as well as fertile controls was examined for haematopoietic stem cells (HSCs) and lymphoid progenitors using three-colour flow cytometry. RESULTS: Significant populations of phenotypic HSCs (CD34+ CD45+ ) were detected in all samples, a high proportion of which co-expressed the differentiation marker CD45RA (45.7%), indicating ongoing differentiation. Almost 30% of uterine HSCs co-expressed CD56 and 44% co-expressed CD7, suggesting the presence of lymphoid progenitors. Small proportions expressed CD127 and CD122, receptors for interleukin (IL)-7 and IL-15, respectively. HSC numbers were similar in the endometrial samples from fertile and infertile women. However, the proportion co-expressing the natural killer (NK) antigen CD56 was significantly increased compared with HSCs found in the endometrium of fertile controls (P = 0.002). CONCLUSIONS: This is the first demonstration of cells with an HSC phenotype in the human endometrium, and increased proportions of NK progenitors in endometrium of women with infertility suggests a dysregulation of this pathway that may contribute to infertility.

Adult↗

Free fetal DNA is not increased before 20 weeks in intrauterine growth restriction or pre-eclampsia.

BACKGROUND: The aim of this study was to quantify maternal plasma fetal DNA and total DNA in early pregnancy in intrauterine growth restriction (IUGR) or pre-eclampsia (PET). METHODS: A nested case control study was carried out in a University Teaching Hospital. Plasma samples were obtained from 1993 women before 20 weeks of gestation. Pregnancies complicated by IUGR or PET were identified and compared to controls. DNA was extracted and real-time quantitative PCR applied for the SRY and beta-actin genes. IUGR or PET groups were compared to controls using the chi(2) and Wilcoxon rank sum tests. RESULTS: SRY was detected in 86% of IUGR (31/36), 94% of PET (15/16) and 78% of controls (56/72). The median SRY was similar in women with IUGR (28 GE/mL) or PET (30.5 GE/mL) and controls (27.5 GE/mL). beta-actin was increased in the IUGR group (3975 GE/mL) compared to controls (1835 GE/mL) (p = 0.045). Cigarette consumption was greater in the IUGR group compared to controls (p = 0.004). CONCLUSIONS: Fetal DNA quantitation in maternal plasma before 20 weeks is not a useful predictor of IUGR or PET. beta-actin levels were elevated before 20 weeks in women with IUGR and may be a marker of maternal susceptibility to this condition.

Actins↗

Does the angle of episiotomy affect the incidence of anal sphincter injury?

OBJECTIVE: Mediolateral episiotomy is associated with lower rates of significant perineal tears than midline episiotomy. However, the relationship between precise angle of episiotomy from the perineal midline and risk of third-degree tear has not been established. This study quantifies this relationship. DESIGN: Case-control study. SETTING: National Maternity Hospital, Dublin, Ireland. SAMPLE: One hundred primiparous women who had undergone right mediolateral episiotomy 3 months previously. METHODS: Two groups of primiparous women were compared. Cases had sustained clinically apparent anal sphincter injury during delivery, while controls had not. The angle of episiotomy measured from the midline was marked on a superimposed sheet of transparent plastic film and measured using a protractor. Data were analysed using Student's t test, chi-square test and logistic regression analysis. MAIN OUTCOME MEASURES: Angle of mediolateral episiotomy from the perineal midline. RESULTS: Fifty-four cases and 46 controls were assessed. Cases were more likely to have undergone assisted delivery and consequently to have been delivered by an obstetrician than by a midwife. The mean angle of episiotomy measured significantly smaller in cases (30 degrees, 95% CI 28-32 degrees) than in controls (38 degrees, 95% CI 35-41 degrees; P<0.001). Analysis showed a 50% relative reduction in risk of sustaining third-degree tear for every 6 degrees away from the perineal midline that an episiotomy was cut. CONCLUSIONS: These results show that a larger angle of episiotomy is associated with a lower risk of third-degree tear and mediolateral episiotomy incisions should be made at as large an angle as possible to minimise the risk of sphincter disruption.

Adolescent↗

Elective Caesarean section is associated with a reduction in developmental dysplasia of the hip in term breech infants.

We wished to establish whether delivery by Caesarean section influenced the incidence of developmental dysplasia of the hip in term breech infants compared with those delivered vaginally. We used maternal charts, singleton term breech presentation, mode of delivery and incidence of developmental dysplasia of the hip for births between January 1997 and October 2002. During the study period 46 089 infants were born. We analysed a total of 941 breech infants of whom 756 were delivered by Caesarean section (515 pre-labour, 241 intrapartum) and 185 vaginally. The incidence of developmental dysplasia of the hip according to the mode of delivery was 19 of 515 (3.69%) following pre-labour Caesarean section, 16 of 241 (6.64%) for intrapartum Caesarean section and 15 of 185 (8.11%) after vaginal delivery. There was a lower incidence of developmental dysplasia of the hip among those infants delivered by elective Caesarean section compared with those delivered vaginally (p < 0.02). These results demonstrate a significantly lower incidence of developmental dysplasia of the hip in term singleton breech births delivered by elective, pre-labour Caesarean section and suggest that labour and delivery influence hip stability in predisposed infants.

Bone Diseases, Developmental↗

Median and ulnar nerve conduction in pregnancy.

OBJECTIVE: A prospective, observational study assessed median and ulnar nerve conduction during pregnancy, to identify the optimum test for differentiating physiological effects of pregnancy from pathological carpal tunnel syndrome (CTS). METHODS: Pregnant women (n=18) and age- and parity-matched non-pregnant controls (n=13) were recruited. Symptomatic and neurophysiological evaluations were performed. Median and ulnar nerve latencies and intrapalmar latency (difference between median and ulnar nerve latencies) were computed. RESULTS: Median nerve distal latency is more prolonged in pregnant women compared with non-pregnant controls. Median nerve latency is more prolonged in pregnant women with symptoms of CTS than in asymptomatic women. The difference between median and ulnar nerve conduction (normal <0.2 ms) discriminates well between symptomatic and asymptomatic pregnant women. CONCLUSIONS: Intrapalmar latency is proposed as a useful diagnostic test for classification of carpal tunnel syndrome during pregnancy.

Carpal Tunnel Syndrome↗

Thirty year trends in a large Irish obstetric cohort.

To evaluate sequential trends in respect of parity, maternal age, gestation at delivery and birthweight in a large cohort of the national birth total during the period 1968 to 1998. Retrospective review of obstetric variables in six biennial cohorts at six yearly intervals, among mothers delivering at the National Maternity Hospital (NMH), Dublin. Where feasible comparisons have been made with contemporary national data. During the thirty year period, total NMH births varied between 11 and 14% of the Irish total. The proportions of primigravidae and grandmultiparae have increased by 15% and decreased by 21% respectively. There has been a shift in the predominant childbearing age group from 25-29 years to the 30-34 years. The proportion of teenage pregnancies has altered very little but births to women over 40 years has declined sharply from 6.0% to 3.0%. Births outside marriage have increased from 5% to 29%. Although, there has been a trend towards increasing average birthweight, no increase was observed in infants exceeding 4.5Kg. Total infants weighing under 1.5Kg have more than doubled. National birth statistics generally reflected NMH trends but with an apparent year time lag.

Birth Rate↗

Influence of persistent occiput posterior position on delivery outcome.

OBJECTIVE: To evaluate the influence of intrapartum persistent occiput posterior position of the fetal head on delivery outcome and anal sphincter injury, with reference to the association with epidural analgesia. METHODS: We conducted a prospective observational study of 246 women with persistent occiput posterior position in labor during a 2-year period, compared with 13,543 contemporaneous vaginal deliveries with occiput anterior position. RESULTS: The incidence of persistent occiput posterior position was significantly greater among primiparas (2.4%) than multiparas (1.3%; P <.001; 95% confidence interval 1.4, 2.4) and was associated with significantly higher incidences of prolonged pregnancy, induction of labor, oxytocin augmentation of labor, epidural use, and prolonged labor. Only 29% of primiparas and 55% of multiparas with persistent occiput posterior position achieved spontaneous vaginal delivery, and the malposition was associated with 12% of all cesarean deliveries performed because of dystocia. Persistent occiput posterior position was also associated with a sevenfold higher incidence of anal sphincter disruption. Despite a high overall incidence of use of epidural analgesia (47% versus 3%), the institutional incidence of persistent occiput posterior position was lower than that reported 25 years ago. CONCLUSION: Persistent occiput posterior position contributed disproportionately to cesarean and instrumental delivery, with fewer than half of the occiput posterior labors ending in spontaneous delivery and the position accounting for 12% of all cesarean deliveries for dystocia. Persistent occiput posterior position leads to a sevenfold increase in the incidence of anal sphincter injury. Use of epidural analgesia was not related to the malposition.

Anal Canal↗

The effects of labour and delivery on the pelvic floor.

Increasing public and professional attention has recently been focused on the issue of both faecal and urinary incontinence following childbirth and these symptoms are sometimes being cited as indications for elective caesarean section. Faecal incontinence has a female-to-male preponderance of 8:1, consistent with childbirth as the principal causative factor, although most symptomatic women do not seek medical advice until after the menopause. Similarly, urinary stress incontinence is almost an exclusively female phenomenon. Obstetric injury may take the form of direct muscular damage to the anal sphincter, as occurs during a third-degree tear, and/or may be the result of cumulative damage to the pudendal nerves. Mechanical, neural and endocrine factors may all play a causative role in faecal incontinence. Symptoms are rarely volunteered by the patient, and may be present for many years after the index pregnancy, and clinical examination alone may fail to detect specific abnormalities. The performance of anal manometry, endoanal ultrasound, urodynamics and neurophysiology studies of the pelvic floor may help to increase the diagnostic yield. Treatment for both urinary and faecal incontinence is available in the form of physiotherapy, fluid and dietary manipulation and in more severe cases, surgery. Adequate primary management of third-degree tears requires careful appraisal as this injury, in particular, is the most important risk factor for subsequent faecal incontinence symptoms. In this chapter we aim to outline the mechanism of damage to the pelvic floor during childbirth, concentrating primarily on anal sphincter damage. We describe the necessary investigations, follow-up and treatment which women with significant pelvic floor damage should receive following delivery, and we finally discuss the issue of further deliveries and, specifically, the current place of caesarean section.

Anal Canal↗

Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsia.

OBJECTIVE: To report plasma concentrations of the adhesion cell molecule P-selectin during pregnancy to determine the effect of subsequent development of hypertension and pre-eclampsia. DESIGN: A longitudinal study. METHODS: A longitudinal study involving 70 women followed up from early pregnancy; 20 who subsequently developed pre-eclampsia were compared with 24 who developed gestational hypertension and 26 normotensive women with normal obstetric outcome. The determination of citrate plasma soluble P-selectin levels throughout pregnancy was performed using a commercial quantitative sandwich immunoassay kit. The temporal course of plasma P-selectin in the three groups of subjects was analysed. RESULTS: There was no significant difference in mean plasma P-selectin concentration between normotensive and gestational hypertensive subjects at any stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at 10-14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean plasma P-selectin concentrations were significantly elevated by 10-14 weeks in women who later developed pre-eclampsia (P < 0.001). CONCLUSIONS: Our data support an inflammatory model for pre-eclampsia whereby endothelial cell activation may be secondary to a primary inflammatory response. Plasma P-selectin has significant potential as a first trimester clinical marker of pre-eclampsia.

Adult↗

Prevalence of hysterectomy in Ireland.

OBJECTIVES: To assess factors influencing the prevalence of hysterectomy in Ireland. METHODS: Analysis of results of a questionnaire completed by a population-based cohort of 17735 women aged 50-65 years attending for breast screening. RESULTS: Prevalence of hysterectomy was 22.2%, was increased in proportion to parity and was higher in younger women, those who had previously used oral contraception and those who had private health insurance; peak age at operation was 45-49 years. CONCLUSION: The relatively high prevalence parity reflects contraceptive practices and utilization of health service resources.

Adult↗

Prospective study of the influence of parity and operative technique on the outcome of primary anal sphincter repair following obstetrical injury.

OBJECTIVE: To determine the influence of parity and method of primary anal sphincter repair on outcome following obstetrical third degree perineal tear. STUDY DESIGN: Prospective study of 154 women after primary repair following third degree tear conducted over 2 years. Postpartum evaluation included a continence questionnaire, anal manometry and endoanal ultrasound. RESULTS: Third degree tears occurred in 1.6% primiparae and 0.6% multiparae during the study period; in 42/112 (38%) primiparae and 10/42 (24%) multiparae, these tears occurred at instrumental deliveries. Mean birthweight (3.8+/-0. 43 kg) was similar in both groups, but prolonged latent second stage of labour (P=0.003), use of epidural analgesia (P<0.0001) and episiotomy extension (P1 quadrant) anal sphincter defect. CONCLUSION: Outcome of anal sphincter repair was not influenced by parity or mode of repair. Despite good symptomatic outcomes, ultrasound evidence of significant anal sphincter injury was found in one-third of patients.

Adolescent↗

Anal vector volume analysis complements endoanal ultrasonographic assessment of postpartum anal sphincter injury.

BACKGROUND: The aim of this study was to determine the role of anal vector manometry in the assessment of postpartum anal sphincter injury and to establish the most suitable method of anal vector volume analysis for identifying significant external anal sphincter (EAS) injury in an at-risk parous population. METHODS: A total of 101 consecutive women with a history of instrumental or traumatic vaginal delivery was recruited. Anal ultrasonography and anal vector manometry were performed. Receiver-operator characteristic curves were used to determine the usefulness of anal manometry and anal vector volume analysis in the identification of significant EAS disruption (full thickness, more than one quadrant involved) detected by ultrasonography. RESULTS: Seventeen women had significant EAS disruption identified by anal ultrasonography. Anal vector manometry provided complementary functional information. Anal vector symmetry index (VSI), determined by analysis of mean maximum squeeze pressure, yielded 100 per cent sensitivity for significant EAS disruption, with a positive predictive value of 61 per cent. CONCLUSION: Anal vector manometry complements endoanal ultrasonography. VSI, determined by means of the squeeze pressure profile, correlates best with significant EAS disruption identified at anal ultrasonography.

Anal Canal↗

A randomized clinical trial comparing primary overlap with approximation repair of third-degree obstetric tears.

OBJECTIVE: We compared, in a prospective, randomized clinical trial, the subjective and objective outcomes after primary anal sphincter overlap or approximation repair of third-degree obstetric tears. STUDY DESIGN: In a prospective, randomized clinical trial at our university teaching hospital, we studied 112 primiparous women who sustained a third-degree tear during a 1-year period (July 1998-June 1999); they were randomly selected, at diagnosis, to receive either an overlap or an approximation repair. Obstetric personnel, trained in both methods, carried out the repairs immediately after delivery. Fifty-five women underwent an overlap procedure, and 57 women underwent an approximation repair. Outcome measures assessed were symptoms of fecal incontinence, abnormal findings on anal manometry, and abnormal findings on endoanal ultrasonography at 3 months post partum. RESULTS: Obstetric factors, including mode of delivery, birth weight, duration of labor, and episiotomy incidence, did not differ significantly between the 2 groups. Experience of the operator, analgesia used, and place of repair were similar in both groups. The median incontinence scores were 0/20 after overlap repair and 2/20 after approximation repair (difference not significant). Eleven women (20%) complained of fecal urgency after overlap repair, in comparison with 17 (30%) after approximation repair (difference not significant). There were no significant differences in either anal manometry or endoanal ultrasonographic results between the 2 groups. Six women (11%) had a significant (>1 quadrant) anal sphincter defect after primary overlap repair, compared with 3 (5%) after approximation repair (difference not significant). Overall, 66% of women had ultrasonographic evidence of a residual full-thickness defect in the external anal sphincter after primary repair. CONCLUSION: The outcome after primary repair of third-degree obstetric tear was similar whether an approximation or an overlap technique was used. Overall symptomatic outcome was good, although two thirds of women had ultrasonographic evidence of residual anal sphincter damage irrespective of the method of repair.

Anal Canal↗

Vaginal birth and perineal trauma.

Vaginal birth has been recognized as being potentially traumatic to the pelvic floor. It is important that contributory obstetric factors are identified and their occurrence minimized. Women who have sustained significant anal sphincter injury are at greater risk of further damage and faecal incontinence with subsequent deliveries. This review reports on recent developments in this field, and examines ways in which morbidity might be reduced.

Anal Canal↗

Menstrual cycle dependent fluctuations in NK and T-lymphocyte subsets from non-pregnant human endometrium.

PROBLEM: To establish the relative proportions of endometrial lymphocyte subpopulations during the menstrual cycle. METHOD OF STUDY: Lymphocytes were investigated by flow cytometry, during the early proliferative (EP), late proliferative (LP), early secretory (ES) and late secretory (LS) phases of the menstrual cycle. RESULTS: Between the LP and LS phases, there was an increase in NK cells from 26.4% to 83.2% (P = 0.0017) of the CD45+ population. T cells decreased from 55.06% to 6.7% (P = 0.0017). Within the T-cell population, CD8+ cells decreased significantly from 63.0% in the LP phase to 54.2% in the LS phase (P = 0.04). In contrast, potential regulatory populations such as double negative (DN) T cells CD3+CD4-CD8- and natural T cells (NT) CD3+CD56+, increased significantly in the LS phase (P = 0.05; P = 0.03). gammadelta T cells, predominantly of the DN and NT phenotypes remained consistently low at all stages of the cycle (2.34%). CONCLUSION: Endometrial lymphocyte fluctuations during the menstrual cycle may reflect hormonal regulation of maternal immunity, thereby promoting tolerance at the time of implantation.

Adult↗

Effect of second vaginal delivery on anorectal physiology and faecal continence: a prospective study.

BACKGROUND: Because obstetric injury to the anal sphincters may be occult, and because the mechanism of injury differs between first and subsequent deliveries, we prospectively assessed the effects of first and second vaginal deliveries on anal physiology and continence. METHODS: We undertook a prospective observational study of 59 previously nulliparous women through two successive vaginal deliveries by means of a bowel-function questionnaire, and an anorectal-physiology assessment, both antepartum and 6-12 weeks post partum. FINDINGS: 13 (22%) women reported altered faecal continence after their first vaginal delivery: eight had persistent symptoms during their second pregnancy, of whom seven deteriorated after the second delivery; five regained continence before their second pregnancy, but two became incontinent again after the second delivery. Five women developed incontinence for the first time after their second vaginal delivery, of whom three had occult primiparous sphincter injury. 20 (34%) women, seven of whom had no symptoms, had anal-sphincter injury as a result of their first delivery, but only two new injuries occurred after the second vaginal delivery (p=0.013). Although pudendal neuropathy was no more common after the second than after the first vaginal delivery (15 vs 19%, p=0.8), pudendal-nerve latency was longer after the second delivery (p=0.02). INTERPRETATION: Primiparous women with persistent symptoms of altered faecal continence experience deterioration after a second vaginal delivery. Women with transient faecal incontinence or occult anal-sphincter injury after their first vaginal delivery are at high risk of faecal incontinence after a second vaginal delivery. The risk of mechanical anal sphincter injury is greatest after the first delivery.

Adult↗

A prospective, randomized study comparing the effect of augmented biofeedback with sensory biofeedback alone on fecal incontinence after obstetric trauma.

PURPOSE: This study was designed to compare prospectively the effects of augmented biofeedback with those of sensory biofeedback alone on fecal incontinence and anorectal manometry after obstetric trauma. METHODS: A consecutive cohort of 40 females with impaired fecal continence after obstetric anal sphincter injury were recruited from a dedicated perineal clinic. Patients were randomly assigned to receive either augmented biofeedback or sensory biofeedback alone. All patients were assessed before and after twelve weeks of biofeedback training, using a fecal continence questionnaire and anorectal manometry. RESULTS: Thirty-nine of 40 females recruited completed the study. Continence scores improved in both treatment groups, but the results were better for those who received augmented biofeedback. Anorectal manometry was unchanged by sensory biofeedback, whereas anal resting and squeeze pressures increased with augmented biofeedback. No change in anal vector symmetry was observed in either group. CONCLUSION: Augmented biofeedback training is superior to sensory biofeedback alone in the treatment of impaired fecal continence after obstetric trauma.

Adult↗