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P R O'Connell

Publications and source records attributed to P R O'Connell.

At least 19 recordsLinked to original sources
PubMed2006

Expression and regulation of connective tissue growth factor by transforming growth factor beta and tumour necrosis factor alpha in fibroblasts isolated from strictures in patients with Crohn's disease.

BACKGROUND: Connective tissue growth factor (CTGF) stimulates fibroblast proliferation and extracellular matrix production. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of CTGF. Stricturing that occurs in patients with Crohn's disease after treatment with anti-tumour necrosis factor (TNF) alpha may be due to dysregulation of CTGF homeostasis. The aim of this study was to examine CTGF expression and regulation in fibroblasts isolated from patients with Crohn's disease. METHODS: Fibroblasts were isolated by a primary explant technique from serosal biopsies of strictured segments of bowel in eight patients undergoing resection for Crohn's disease and from normal colon in seven patients having resection for benign or malignant colorectal disease. Cells were stimulated with transforming growth factor (TGF) beta and TNF-alpha. CTGF protein and mRNA expression were measured by western blotting and real-time polymerase chain reaction respectively. RESULTS: Mean(s.d.) CTGF protein expression in strictured Crohn's fibroblasts was higher than that in normal fibroblasts (56.5(9.7) versus 17.0(10.0) respectively; P = 0.011). In normal and strictured Crohn's fibroblasts, culture with TGF-beta increased CTGF protein and mRNA expression. Co-culture of normal fibroblasts with TNF-alpha suppressed TGF-beta-stimulated CTGF expression. CONCLUSION: : Increased expression of CTGF in strictured Crohn's fibroblasts underlies its role in fibrosis. TNF-alpha suppresses fibrosis by downregulating fibroblast CTGF expression, an effect that may be lost following anti-TNF-alpha treatment, thereby promoting stricture formation.

Adult↗
PubMed2006

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↗
PubMed2005

Hyaluronidase assisted reduction of intestinal intussusception; a novel application.

Failed manual reduction of entero-enteric intussusception in adults leads to intestinal resection for benign disease. The case of a twenty-year old male with an eight inch jejuno-jejunal intussusception is presented. The authors resected a hamartomatous polyp from the apex of the intussusceptum and a subsequent attempt at manual reduction was unsuccessful. Hyaluronidase was injected into the neck of the intussusception and dissipation of tissue oedema facilitated reduction within two minutes. To our knowledge, this is the first reported case of this application of Hyaluronidase.

Adult↗
PubMed2004

Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is implicated in early wound healing and fibrosis. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of VEGF. The aim of this study was to examine VEGF expression and regulation in fibroblasts isolated from patients with Crohn's disease. METHODS: Fibroblasts were isolated by a primary explant technique from serosal biopsies of non-strictured and strictured segments of bowel from eight patients undergoing resection for Crohn's disease, and normal colon from six patients undergoing resection for benign and malignant colorectal disease. Fibroblasts were cultured with transforming growth factor (TGF) beta and corticosteroids. After 24 h the culture supernatant was collected for VEGF assay by enzyme-linked immunosorbent assay. RESULTS: VEGF production was significantly higher in fibroblasts isolated from strictures (mean(s.e.m.) 1980(260) pg/ml) than from non-strictured segments (1116(165) pg/ml) in patients with Crohn's disease or control fibroblasts (898(93) pg/ml). TGF-beta increased VEGF production in normal and non-strictured Crohn's fibroblasts. Corticosteroids suppressed unstimulated VEGF production in all groups. CONCLUSION: Enhanced serosal fibroblast VEGF production might play a role in initiating stricture formation in Crohn's disease. VEGF production in serosal fibroblasts is sensitive to stimulation with TGF-beta. Corticosteroids may reduce stricturing through suppression of VEGF.

Adult↗
PubMed2003

Sentinel lymph node mapping in colorectal cancer.

BACKGROUND: Ultrastaging, by serial sectioning combined with immunohistochemical techniques, improves detection of lymph node micrometastases. Sentinel lymph node mapping and retrieval provides a representative node(s) to facilitate ultrastaging. The impact on staging of carcinoma of the colon and rectum in all series emphasizes the importance of this technique in cancer management. Now the challenge is to determine the biological relevance and prognostic implications. METHODS: The electronic literature (1966 to present) on sentinel node mapping in carcinoma of the colon and rectum was reviewed. Further references were obtained by cross-referencing from key articles. RESULTS: Lymphatic mapping appears to be readily applicable to colorectal cancer and identifies those lymph nodes most likely to harbour metastases. Sentinel node mapping carries a false-negative rate of approximately 10 per cent in larger studies, but will also potentially upstage a proportion of patients from node negative to node positive following the detection of micrometastases. The prognostic implication of these micrometastases requires further evaluation. CONCLUSION: Further follow-up to assess the prognostic significance of micrometastases in colorectal cancer is required before the staging benefits of sentinel node mapping can have therapeutic implications.

Colorectal Neoplasms↗
PubMed2001

Advantages of a posterior fourchette incision in anal sphincter repair.

PURPOSE: Delayed repair of obstetric-related anal sphincter injury remains problematic, and perineal wound breakdown is common. The aim of this study was to assess the outcome after overlap anal sphincter repair and to determine the advantages, if any, of a posterior fourchette incision (n = 18) compared with a conventional perineal incision (n = 32). METHODS: Fifty females of mean parity 2.8 (standard deviation, 1.6) underwent repair in a five-year period. The mean follow-up was 23 months. Assessment was by anal vector manometry, endoanal ultrasound, and continence scoring. RESULTS: Functional outcomes were similar in the two groups. Repair increased squeeze-pressure increment and improved continence scores in both groups. Postoperative wound complications were fewer when a posterior fourchette incision was used compared with a perineal incision (11 vs. 44 percent, respectively; P < 0.05). CONCLUSIONS: Delayed anal sphincter repair improves continence. A posterior fourchette approach is associated with fewer postoperative wound complications without compromising the quality of repair and the functional outcome.

Adult↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Stricture formation in Crohn's disease: the role of intestinal fibroblasts.

OBJECTIVE: To determine whether intestinal fibroblasts in patients with Crohn's disease (CD) have an enhanced capacity to reorganize collagen and thus cause stricture formation. SUMMARY BACKGROUND DATA: Stricture formation is a characteristic feature of CD that may distinguish it from other forms of inflammatory bowel disease. Methods Fibroblasts were obtained at surgery from the colon and ileum of patients with CD and ulcerative colitis (UC) and control patients. Primary fibroblast cultures were obtained by explant technique. Fibroblast contractile activity was measured using fibroblast-populated collagen lattices (FPCLs), in which the cultured fibroblasts were seeded in free-floating collagen gel matrices that they reorganize and contract. Fibroblast contractile activity was measured as the reduction of surface area (mm2) of collagen gel matrix at 24-hour intervals for 1 week. RESULTS: Fibroblasts from patients with CD displayed enhanced capacity to contract FPCL when compared to UC and control fibroblasts. This activity was maximal in fibroblasts recovered from strictured regions in CD. Fibroblasts from patients with UC had a contractile capacity similar to that of controls. Hydrocortisone inhibited this in vitro contractile activity in a dose-dependent manner. CONCLUSIONS: Intestinal fibroblasts in CD possess enhanced capacity for collagen reorganization and contractile activity in vitro. This activity may be responsible for stricture formation in CD.

Cell Line↗
PubMed2000

Neutrophil apoptosis is delayed in patients with inflammatory bowel disease.

Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohn's disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.

Adolescent↗
PubMed1999

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↗
PubMed1999

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↗