• A case of toxoplasmosis causing severe ventriculomegaly in association with reproductive immunotherapy.

      O'Connor, C; Stuart, B; Turner, M J; Kennelly, M M; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland. drclare.oconnor@gmail.com (2012-08)
    • Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

      Gasch, Claudia; Ffrench, Brendan; O'Leary, John J; Gallagher, Michael F (BioMed Central, 2017)
      It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.
    • Cerebral tissue oxygenation index and superior vena cava blood flow in the very low birth weight infant.

      Moran, M; Miletin, J; Pichova, K; Dempsey, E M; Department of Pediatrics and Newborn Medicine, Coombe Women and Infants, University Hospital, Dublin 8, Ireland. (2012-02-01)
      BACKGROUND: Superior vena cava (SVC) flow assesses blood flow from the upper body, including the brain. Near infrared spectroscopy (NIRS) provides information on brain perfusion and oxygenation. AIM: To assess the relationship between cerebral tissue oxygenation index (cTOI) and cardiac output measures in the very low birth weight (VLBW) infant in the first day of life. METHODS: A prospective observational cohort study. Neonates with birth weight less than 1500 g (VLBW) were eligible for enrollment. Newborns with congenital heart disease, major congenital malformations and greater than Papile grade1 Intraventricular Haemorrhage on day 1 of life were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Low SVC flow states were defined as a flow less than 40 mL/kg/min. cTOI was measured using NIRO 200 Hamamatsu. RESULTS: Twenty-seven VLBW neonates had both echocardiography and NIRS performed. The median (range) gestation was 29/40 (25 + 3 to 31 + 5 weeks) and median birth weight was 1.2 kg (0.57-1.48 kg). The mean (SD) TOI was 68.1 (7.9)%. The mean (SD) SVC flow was 70.36(39.5) mLs/kg/min. The correlation coefficient of cerebral tissue oxygenation and SVC flow was r = 0.53, p-value 0.005. There was a poor correlation between right and left ventricular output and cTOI which is not surprising considering the influence of intra- and extracardiac shunts. CONCLUSION: There is a positive relationship between cerebral TOI values and SVC flow in the very low birth infant on day one of life.
    • Chlamydia trachomatis detection in cervical PreservCyt specimens from an Irish urban female population.

      Keegan, H; Ryan, F; Malkin, A; Griffin, M; Lambkin, H; Department of Pathology, Coombe Women's Hospital, Dublin, Ireland., keeganh28@gmail.com (2012-02-01)
      OBJECTIVE: The aim of this study was to determine the prevalence of cervical Chlamydia trachomatis infection by polymerase chain reaction (PCR) in urban women undergoing routine cervical cytological screening and to investigate the relationship with age, cytology, smoking status and concurrent human papillomavirus (HPV) infection. METHODS: A total of 996 women (age range 16-69 years) attending general practitioners for routine liquid-based cervical smear screening in the Dublin area were recruited in the study of prevalence of C. trachomatis. Informed consent was obtained and liquid-based cytology (LBC) specimens were sent for cytological screening. DNA was extracted from residual LBC and tested for C. trachomatis by PCR using the highly sensitive C. trachomatis plasmid (CTP) primers and for HPV infection using the MY09/11 primers directed to the HPV L1 gene in a multiplex format. RESULTS: The overall prevalence of C. trachomatis was 5.4%. Prevalence was highest in the <25 years age group (10%). Coinfection with HPV and C. trachomatis occurred in 1% of the screening population. A higher rate of smoking was observed in women positive for C. trachomatis, HPV infections or those with abnormal cervical cytology. Chlamydia trachomatis infection was not associated with abnormal cytology. CONCLUSIONS: Women (5.4%) presenting for routine cervical screening are infected with C. trachomatis. Opportunistic screening for C. trachomatis from PreservCyt sample taken at the time of cervical cytological screening may be a possible strategy to screen for C. trachomatis in the Irish female population.
    • Chronic illness and multimorbidity among problem drug users: a comparative cross sectional pilot study in primary care.

      Cullen, Walter; O'Brien, Sarah; O'Carroll, Austin; O'Kelly, Fergus D; Bury, Gerard; UCD School of Medicine and Medical Science, Coombe Healthcare Centre, Dublin,, Ireland. walter.cullen@ucd.ie (2012-02-01)
      BACKGROUND: Although multimorbidity has important implications for patient care in general practice, limited research has examined chronic illness and health service utilisation among problem drug users. This study aimed to determine chronic illness prevalence and health service utilisation among problem drug users attending primary care for methadone treatment, to compare these rates with matched 'controls' and to develop and pilot test a valid study instrument. METHODS: A cross-sectional study of patients attending three large urban general practices in Dublin, Ireland for methadone treatment was conducted, and this sample was compared with a control group matched by practice, age, gender and General Medical Services (GMS) status. RESULTS: Data were collected on 114 patients. Fifty-seven patients were on methadone treatment, of whom 52(91%) had at least one chronic illness (other then substance use) and 39(68%) were prescribed at least one regular medication. Frequent utilisation of primary care services and secondary care services in the previous six months was observed among patients on methadone treatment and controls, although the former had significantly higher chronic illness prevalence and primary care contact rates. The study instrument facilitated data collection that was feasible and with minimal inter-observer variation. CONCLUSION: Multimorbidity is common among problem drug users attending general practice for methadone treatment. Primary care may therefore have an important role in primary and secondary prevention of chronic illnesses among this population. This study offers a feasible study instrument for further work on this issue. (238 words).
    • A cohort study of maternal and neonatal morbidity in relation to use of sequential instruments at operative vaginal delivery.

      Murphy, Deirdre J; Macleod, Maureen; Bahl, Rachna; Strachan, Bryony; Academic Department of Obstetrics & Gynaecology, Coombe Women & Infants, University Hospital & Trinity College, University of Dublin, Dublin 8, Ireland., deirdre.j.murphy@tcd.ie (2012-02-01)
      OBJECTIVE: To evaluate the risk factors and maternal and neonatal morbidity associated with sequential use of instruments (vacuum and forceps) at operative vaginal delivery. STUDY DESIGN: A cohort study of 1360 nulliparous women delivered by a single instrument (vacuum or forceps) or by both instruments, within two university teaching hospitals in Scotland and England. Outcomes were compared for use of sequential instruments versus use of any single instrument. A sub-group analysis compared sequential instruments versus forceps alone. Outcomes of interest included anal sphincter tears, postpartum haemorrhage, urinary retention, urinary incontinence, prolonged hospital admission, neonatal trauma, low Apgar scores, abnormal cord bloods and admission to the neonatal intensive care unit (NICU). RESULTS: Use of sequential instruments at operative vaginal delivery was associated with fetal malpositions, Odds Ratio (OR) 1.8 (95% Confidence Interval (CI) 1.3-2.6), and large neonatal head circumference (>37 cm) (OR 5.0, 95% CI 2.6-9.7) but not with maternal obesity or grade of operator. Sequential use of instruments was associated with greater maternal and neonatal morbidity than single instrument use (anal sphincter tear 17.4% versus 8.4%, adjusted OR 2.1, 95% CI 1.2-3.3; umbilical artery pH <7.10, 13.8% versus 5.0%, adjusted OR 3.3, 95% CI 1.7-6.2). Sequential instrument use had greater morbidity than single instrument use with forceps alone (anal sphincter tear OR 1.8, 95% CI 1.1-2.9; umbilical artery pH <7.10 OR 3.0, 95% CI 1.7-5.5). CONCLUSIONS: The use of sequential instruments significantly increases maternal and neonatal morbidity. Obstetricians need training in the appropriate selection and use of instruments with the aim of completing delivery safely with one instrument.
    • Comparison in maternal body composition between Caucasian Irish and Indian women.

      Farah, N; Murphy, M; Ramphul, M; O'Connor, N; Kennelly, M M; Turner, M J; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, , Dublin, Ireland. nadine.farah@ucd.ie (2012-02-01)
      The use of body mass index (BMI) for the diagnosis of obesity has limitations, especially when comparing ethnic groups with different body proportions. The aim of this prospective study was to compare maternal body composition in early pregnancy between Caucasian Irish and Indian women. A total of 81 Indian women and 81 Irish Caucasian women were matched for age, parity and BMI. Maternal weight and height were measured, and body composition analysed using bioelectrical impedance. The Irish women were taller and weighed more than the Indian women (p<0.001). At any given BMI, the Indian women had a higher total body fat percentage, visceral fat level and high fat percentage than the Irish women (p=0.024, 0.001 and 0.001, respectively). Our findings suggest that lower BMI cut-offs should be used for screening for gestational diabetes mellitus in Indian women attending our antenatal services.
    • A comparison of blood pressure measurements in newborns.

      O'Shea, Joyce; Dempsey, Eugene M; Department of Newborn Medicine, Coombe Women's Hospital, Dublin, Ireland. (2012-02-01)
      Blood pressure monitoring is an essential component of neonatal intensive care. We compared invasive and noninvasive (Dinamap, Marquette, and Dash) recordings in newborns and also noninvasive values obtained from upper and lower limbs. Infants' blood pressure was recorded every 6 hours for 72 hours using three noninvasive devices and compared with invasive readings taken simultaneously. Twenty-five babies were enrolled in the study, with birth weights of 560 to 4500 g and gestation 24 + 1 to 40 + 5 weeks. Three hundred thirty-two recordings were obtained. Comparison between invasive and noninvasive readings revealed that all three noninvasive monitors overread mean blood pressure. There was no significant difference between the cuff recordings obtained from the upper or lower limbs. All three noninvasive devices overestimated mean blood pressure values compared with invasive monitoring. Clinicians may be falsely reassured by noninvasive monitoring. Mean blood pressure values obtained from the upper and lower limb are similar.
    • Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

      Keegan, Helen; Mc Inerney, Jamie; Pilkington, Loretto; Gronn, Petter; Silva, Ivan; Karlsen, Frank; Bolger, Noel; Logan, Catriona; Furuberg, Liv; O'Leary, John; et al. (2012-02-01)
      Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205/299) of the cases were positive by hc2 and 38% (112/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.
    • A comparison of maternal and paternal body mass index in early pregnancy.

      Kelly, Ross; Farah, Nadine; O'Connor, Norah; Kennelly, Mairead; Stuart, Bernard; Turner, Michael J; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland. (2011-04)
       To determine the body mass index (BMI) and the body composition of fathers-to-be and to compare the findings with those of mothers-to-be during early pregnancy.
    • A complication after a previous caesarean section.

      Barrett, Niamh; Sheehan, Sharon R; Murphy, Deirdre J; Coombe Women and Infants' University Hospital, Dublin 8, Ireland. (2012-02-01)
    • Continuation of metformin in the first trimester of women with polycystic ovarian syndrome is not associated with increased perinatal morbidity.

      Bolton, S; Cleary, B; Walsh, J; Dempsey, E; Turner, M J; UCD School of Medicine and Medical Science, Coombe Women's Hospital, Dublin 8,, Ireland. (2012-02-01)
      This study aimed to assess the perinatal outcome, especially foetal growth, following the continuation of metformin during the first trimester of pregnancy. All women with polycystic ovary syndrome (PCOS) treated with metformin in the first trimester and who delivered a baby weighing 500 g or more between 2003 and 2005 were studied. Subjects were matched for age and parity with randomly selected controls. The perinatal outcomes studied were: growth parameters, gestational age, congenital defects, hypoglycaemia and neonatal unit admission. Sixty-six pregnancies were compared with 66 controls; all had singleton deliveries. There was no difference in mean birth weight between the metformin and the control groups (p=0.84). The percentage of small (<10th centile) and large (>90th centile) for gestational age babies was lower in the metformin group. In the metformin group, there were no major congenital malformations and 24% of the babies were admitted to the neonatal intensive care unit (NICU) compared with 27% of the babies in the control group (non-significant). Neonatal hypoglycaemia was less common in the metformin group (18.5% vs. 24.5%) and fewer babies required intravenous glucose therapy (6.3% vs. 12%). We found no evidence that the continuation of metformin in the first trimester of pregnancy was associated with an adverse foetal outcome.
    • Correlation between birth weight and maternal body composition.

      Kent, Etaoin; O'Dwyer, Vicky; Fattah, Chro; Farah, Nadine; O'Connor, Clare; Turner, Michael J; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland. ekent@rcsi.ie (2013-01)
      To estimate which maternal body composition parameters measured using multifrequency segmental bioelectric impedance analysis in the first trimester of pregnancy are predictors of increased birth weight.
    • Correlation between maternal inflammatory markers and fetomaternal adiposity.

      Farah, Nadine; Hogan, Andrew E; O'Connor, Norah; Kennelly, Mairead M; O'Shea, Donal; Turner, Michael J; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin 8, Ireland. drnfarah@gmail.com (2012-10)
      Outside pregnancy, both obesity and diabetes mellitus are associated with changes in inflammatory cytokines. Obesity in pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or fetal macrosomia. The objective of this study was to determine the correlation between maternal cytokines and fetomaternal adiposity in the third trimester in women where the important confounding variable GDM had been excluded. Healthy women with a singleton pregnancy and a normal glucose tolerance test at 28 weeks gestation were enrolled at their convenience. Maternal cytokines were measured at 28 and 37 weeks gestation. Maternal adiposity was assessed indirectly by calculating the Body Mass Index (BMI), and directly by bioelectrical impedance analysis. Fetal adiposity was assessed by ultrasound measurement of fetal soft tissue markers and by birthweight at delivery. Of the 71 women studied, the mean maternal age and BMI were 29.1 years and 29.2 kg/m(2) respectively. Of the women studied 32 (45%) were obese. Of the cytokines, only maternal IL-6 and IL-8 correlated with maternal adiposity. Maternal TNF-α, IL-β, IL-6 and IL-8 levels did not correlate with either fetal body adiposity or birthweight. In this well characterised cohort of pregnant non-diabetic women in the third trimester of pregnancy we found that circulating maternal cytokines are associated with maternal adiposity but not with fetal adiposity.
    • Day-surgery patients anesthetized with propofol have less postoperative pain than those anesthetized with sevoflurane.

      Tan, Terry; Bhinder, Rajesh; Carey, Michael; Briggs, Liam; Department of Anaesthesia and Perioperative Medicine, Coombe Women and Infants, University Hospital, Cork St., Dublin 8, Ireland. tutan@me.com (2012-02-01)
      BACKGROUND: There have been recent studies suggesting that patients anesthetized with propofol have less postoperative pain compared with patients anesthetized with volatile anesthetics. METHODS: In this randomized, double-blind study, 80 patients undergoing day-case diagnostic laparoscopic gynecological surgery were either anesthetized with IV propofol or sevoflurane. The primary outcome measured was pain on a visual analog scale. RESULTS: Patients anesthetized with propofol had less pain compared with patients anesthetized with sevoflurane (P = 0.01). There was no difference in any of the other measured clinical outcomes. CONCLUSIONS: The patients anesthetized with propofol appeared to have less pain than patients anesthetized with sevoflurane.