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Morris R.K.,University of Birmingham | Morris R.K.,Foundation Medicine | Riley R.D.,University of Birmingham | Doug M.,Birmingham Womens Hospital NHS Foundation Trust | And 3 more authors.
BMJ (Online) | Year: 2012

Objective To determine the diagnostic accuracy of two "spot urine" tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive.] However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). Conclusion The maternal "spot urine" estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome.


Patzlaff J.S.,University of Wisconsin - Oshkosh | Patzlaff J.S.,R and D Systems Inc | Terrenoire E.,University of Birmingham | Terrenoire E.,Birmingham Womens Hospital NHS Foundation Trust | And 3 more authors.
Experimental Cell Research | Year: 2010

Histone acetylation is a key modification that regulates chromatin accessibility. Here we show that treatment with butyrate or other histone deacetylase (HDAC) inhibitors does not induce histone hyperacetylation in metaphase-arrested HeLa cells. When compared to similarly treated interphase cells, acetylation levels are significantly decreased in all four core histones and at all individual sites examined. However, the extent of the decrease varies, ranging from only slight reduction at H3K23 and H4K12 to no acetylation at H3K27 and barely detectable acetylation at H4K16. Our results show that the bulk effect is not due to increased or butyrate-insensitive HDAC activity, though these factors may play a role with some individual sites. We conclude that the lack of histone acetylation during mitosis is primarily due to changes in histone acetyltransferases (HATs) or changes in chromatin. The effects of protein phosphatase inhibitors on histone acetylation in cell lysates suggest that the reduced ability of histones to become acetylated in mitotic cells depends on protein phosphorylation. © 2010 Elsevier Inc.


Israfil-Bayli F.,Birmingham Womens Hospital NHS Foundation Trust | Toozs-Hobson P.,Birmingham Womens Hospital NHS Foundation Trust | Lees C.,University of Cambridge | Slack M.,University of Cambridge | And 2 more authors.
Medical Hypotheses | Year: 2013

Cervical weakness is an important cause of late miscarriage and extreme preterm labour. Women have been traditionally offered a cervical cerclage procedure, though studies failed to demonstrate a therapeutic effect. None of these studies has addressed the effect of non-braided to braided suture material on cerclage outcome. Type of suture material is an important determinant of surgical outcomes. This issue is of particular relevance to cerclage because the traditionally braided suture has been associated with increased risk of infection in other surgical procedures. Indeed, infection is an important underlying cause for cerclage failure. It is for this reason that some surgeons use non-braided suture material. Therefore, we hypothesise that the unrealised benefit of cervical cerclage is at least in part due to the type of suture material used. In this article, we present the rationale behind our hypothesis and a proposed way of testing it. © 2013 Elsevier Ltd.


Drozniewska M.,Nicolaus Copernicus University | Drozniewska M.,Birmingham Womens Hospital NHS Foundation Trust | Haus O.,Nicolaus Copernicus University | Haus O.,Wroclaw Medical University
Molecular Cytogenetics | Year: 2014

Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ∼862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype. © 2014 Drozniewska and Haus; licensee BioMed Central Ltd.


Hill M.,Great Ormond Street Hospital for Children NHS Trust | Lewis C.,Genetic Alliance UK | Jenkins L.,Great Ormond Street Hospital for Children NHS Trust | Allen S.,Birmingham Womens Hospital NHS Foundation Trust | And 2 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Introduction : Fetal sex determination has traditionally been performed in pregnancies at risk of sex-linked genetic conditions by analysis of chorionic villi or amniocytes following invasive tests. The development of noninvasive prenatal diagnosis (NIPD) using cell-free fetal DNA in maternal plasma has allowed women to have accurate information about fetal sex early in pregnancy without the risk of miscarriage. Areas covered : In the UK, NIPD for fetal sex determination has been offered on a research basis since 2003. Formal approval and regulation through national bodies is essential to ensure standardized laboratory services, appropriate funding and equity of access for service users. Here we describe the process of formal commissioning that has been supported by a multifaceted approach to service evaluation, including appraisal of analytical and clinical validity, clinical utility and economic costs together with an exploration of service users' and providers' attitudes, preferences and information needs. Expert opinion : Implementation strategies that reach beyond the assessment of laboratory test parameters to consider psychosocial and economic issues have been crucial in bringing NIPD for fetal sex determination into routine practice. Ongoing audit and monitoring of service delivery will ensure a high standard of care is maintained. © 2012 Informa UK, Ltd.


Israfil-Bayli F.,Birmingham Womens Hospital NHS Foundation Trust | Toozs-Hobson P.,Birmingham Womens Hospital NHS Foundation Trust | Lees C.,Imperial College London | Slack M.,University of Cambridge | Ismail K.,University College Birmingham
Trials | Year: 2015

Background: Cervical incompetence is one of the causes of preterm birth and mid-trimester pregnancy loss. Cervical cerclage is a surgical procedure to treat cervical incompetence. Cervical cerclage reduces the incidence of preterm birth in women at risk of recurrent preterm birth, without a statistically significant reduction in perinatal mortality or neonatal morbidity. Multifilament/braided sutures such as Mersilene tape have been traditionally used for cervical cerclage. Braided sutures, particularly mesh-like non-absorbable sutures, have been associated with an increased risk of infection and, hence, some obstetricians prefer to use monofilament/non-braided sutures. However, these claims are not substantiated by any scientific or clinical evidence. Methods/Design: Women eligible for elective or ultrasound-indicated cerclage at 12 to 21 + 6 weeks of gestation will be randomised to having the procedure using either a monofilament non-braided suture (Ethilon) or a Multifilament braided suture (Mersilene tape) inserted using a McDonald technique. Consent for participation in the Cerclage outcome by the type of suture (COTS) study will be obtained from each eligible participant. Clinical trials registration: COTS is registered with the International Standard Research for Clinical Trials (ISRCTN17866773). Registered on 27 March 2013. © 2014 Israfil-Bayli et al.; licensee BioMed Central Ltd.


Burton H.,Foundation for Genomics and Population Health | Cole T.,Birmingham Womens Hospital NHS Foundation Trust | Lucassen A.M.,University of Southampton
Clinical Medicine, Journal of the Royal College of Physicians of London | Year: 2012

Medicine has always striven to personalise or stratify approaches towards individual patients, but recently these terms have been applied particularly to denote improved disease sub-classification achieved through new genetic and genomic technologies. Techniques to analyse a person's genetic code have improved in sensitivity exponentially over recent years and at the same time the cost of such analyses has become affordable to routine NHS care. This article highlights the significant opportunities that genomics brings to healthcare, as well as some of the practical and ethical challenges. © Royal College of Physicians, 2012. All rights reserved.


Toozs-Hobson P.,Birmingham Womens Hospital NHS Foundation Trust | Swift S.,Medical University of South Carolina
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2014

The Pelvic Organ Prolapse Quantification (POP-Q) staging system revolutionized the way we look at prolapse and gave us a much needed universal objective system that has helped in research and informing patients. The system is now 16 years old, and as our knowledge has increased, so has the realization that this system needs an overhaul in defining stage 1 "prolapse." © 2014 The International Urogynecological Association.


Patel C.,Birmingham Womens Hospital NHS Foundation Trust | Cooper-Charles L.,Birmingham Womens Hospital NHS Foundation Trust | McMullan D.J.,Birmingham Womens Hospital NHS Foundation Trust | Walker J.M.,Birmingham Womens Hospital NHS Foundation Trust | And 2 more authors.
European Journal of Human Genetics | Year: 2011

Gilles de la Tourette syndrome is a complex neuropsychiatric disorder with a strong genetic basis. We identified a male patient with Tourette syndrome-like tics and an apparently balanced de novo translocation 46,XY,t(2;7)(p24.2;q31). Further analysis using array comparative genomic hybridisation (CGH) revealed a cryptic deletion at 7q31.1-7q31.2. Breakpoints disrupting this region have been reported in one isolated and one familial case of Tourette syndrome. In our case, IMMP2L, a gene coding for a human homologue of the yeast inner mitochondrial membrane peptidase subunit 2, was disrupted by the breakpoint on 7q31.1, with deletion of exons 1-3 of the gene. The IMMP2L gene has previously been proposed as a candidate gene for Tourette syndrome, and our case provides further evidence of its possible role in the pathogenesis. The deleted region (7q31.1-7q31.2) of 7.2 Mb of genomic DNA also encompasses numerous genes, including FOXP2, associated with verbal dyspraxia, and the CFTR gene. © 2011 Macmillan Publishers Limited All rights reserved.


PubMed | Birmingham Womens Hospital NHS Foundation Trust
Type: | Journal: Current opinion in obstetrics & gynecology | Year: 2017

Noninvasive prenatal diagnosis for single gene disorders is coming to fruition in its clinical utility. The presence of cell-free DNA in maternal plasma has been recognized for many years, and a number of applications have developed from this. Noninvasive prenatal diagnosis for single gene disorders has lagged behind due to complexities of technology development, lack of investment and the need for validation samples for rare disorders.Publications are emerging demonstrating a variety of technical approaches and feasibility of clinical application. Techniques for analysis of cell-free DNA including digital PCR, next-generation sequencing and relative haplotype dosage have been used most often for assay development. Analysis of circulating fetal cells in the maternal blood is still being investigated as a viable alternative and more recently transcervical trophoblast cells. Studies exploring ethical and social issues are generally positive but raise concerns around the routinization of prenatal testing.Further work is necessary to make testing available to all patients with a pregnancy at risk of a single gene disorder, and it remains to be seen if the development of more powerful technologies such as isolation and analysis of single cells will shift the emphasis of noninvasive prenatal diagnosis. As testing becomes possible for a wider range of conditions, more ethical questions will become relevant.

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