James Walker
University of Leeds, Medicine, Faculty Member
Research Interests:
There is widespread evidence of inflammatory cell and antioxidant activity in preeclampsia. However, it is difficult to disentangle the pathological changes from the normal physiological responses to the pathological process. The site at... more
There is widespread evidence of inflammatory cell and antioxidant activity in preeclampsia. However, it is difficult to disentangle the pathological changes from the normal physiological responses to the pathological process. The site at which the measurements are taken, and the severity of disease, alter the results. The interaction between the mother and the fetus needs to be considered separately, especially when the genetics of preeclampsia is considered. It is clear that within the placenta, there is an increase in tumor necrosis factor-alpha (TNF-alpha) and lipid peroxide production. These changes are associated with a reduction in the various placental antioxidants. This suggests there may be a failure of the normal fetal protection systems. Lipid peroxidation is also increased in the peripheral blood, as well as IL-6, IL-8, and TNF-alpha, which are of monocytic origin. Stimulated monocytes produce free radicals, which can cause oxidative damage. Maternal cells protect themselves with both plasma and intracellular antioxidants. There is an imbalance between oxidant and antioxidant activity in preeclampsia. Changes in membrane oxidation can lead to changes in the membrane stability. Genetic difference in the production of TNF-alpha and nitric oxide may also modify the disease process, demonstrating the role for "moderator genes."
Research Interests:
The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2,... more
The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (+/-SEM). PET featured significantly higher IL-1beta, IL-2, IL-10, IL-13, G-CSF, IFN-gamma, MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.
Research Interests: Immunology, Cytokines, Inflammation, Adolescent, Medicine, and 15 moreLipopolysaccharide, Pregnancy, Humans, Preeclampsia, Female, Male, Lipopolysaccharides, Adult, Tumor necrosis factor-alpha, Pre Eclampsia, Inflammatory response, Whole-blood, Monocyte, Paediatrics and reproductive medicine, and In Vitro Techniques
Research Interests:
Pelvic pain is a common debilitating condition. Most investigations are invasive, expensive and usually negative. Although a positive diagnosis of endometriosis justifies a recognized treatment programme, the majority of women with... more
Pelvic pain is a common debilitating condition. Most investigations are invasive, expensive and usually negative. Although a positive diagnosis of endometriosis justifies a recognized treatment programme, the majority of women with negative investigations are left without a diagnosis and often accused of psychological abnormalities. The reasons for the negative investigations are just as likely to be due to the inadequate techniques of the operator as the lack of pathological signs. The early use of menstrual suppression with GnRH analogue allows pain relief sooner in the majority of sufferers and separates those with pain related to the menstrual cycle, from whatever cause, from those whose pain is not related to pelvic physiology and who would not benefit from further medication or operative therapy. The majority, who have obtained relief from the analogue therapy, then have time to discuss alternative long-term treatments without the feeling of desperation that chronic monthly pe...
Research Interests:
Ectopic pregnancy is a major gynecologic emergency, which results in significant morbidity for the mother and inevitable loss of the pregnancy. Its presentation can be varied from minor symptoms to sudden collapse. It produces a... more
Ectopic pregnancy is a major gynecologic emergency, which results in significant morbidity for the mother and inevitable loss of the pregnancy. Its presentation can be varied from minor symptoms to sudden collapse. It produces a diagnostic dilemma and a management problem. With advances in medical care, most women survive ectopic pregnancy and many will be diagnosed early enough to allow conservative management with the resulting lower morbidity and possible anatomic conservation. This article covers what is currently known about the etiology of this condition, the best approach to the diagnoses and management and the long-term consequences for the women concerned.
Research Interests:
Background Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal... more
Background Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low. The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women. Methods and Results Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in NP (38±6.6 impulses/100 beats) was greater ( P <0.05) than in NN women (19±1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women ( P <0.001) (146±23...
Research Interests: Electrophysiology, Evolution, Adolescent, Comparative Study, Electrocardiography, and 15 moreComplication, Humans, Hypertension, Blood Pressure, Female, Exploration, Clinical Sciences, Longitudinal Studies, Adult, Circulation, European Continental Ancestry Group, Baroreflex, Action Potentials, Gestation, and Cardiovascular medicine and haematology
Research Interests:
Research Interests:
Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C&amp;amp;amp;amp;amp;amp;gt;T), toll-like receptor (TLR)-2 +2258 (G&amp;amp;amp;amp;amp;amp;gt;A) and matrix metalloproteinase (MMP)-9 -1562... more
Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 -590 (C&amp;amp;amp;amp;amp;amp;gt;T), toll-like receptor (TLR)-2 +2258 (G&amp;amp;amp;amp;amp;amp;gt;A) and matrix metalloproteinase (MMP)-9 -1562 (C&amp;amp;amp;amp;amp;amp;gt;T) were examined by polymerase chain reaction-restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James&amp;amp;amp;amp;amp;amp;#39;s University Hospital. While the TLR-2 +2258 (G&amp;amp;amp;amp;amp;amp;gt;A) and MMP-9 -1562 (C&amp;amp;amp;amp;amp;amp;gt;T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 -590 (C&amp;amp;amp;amp;amp;amp;gt;T) SNP and pre-eclampsia (chi(2)= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350).
Research Interests:
Research Interests:
Research Interests:
Research Interests: Water, Medicine, Pregnancy, Humans, Baths, and 3 moreFemale, Prenatal Care, and Medical and Health Sciences
A book of 50 or so of the most common presenting symptoms in obstetrics and gynaecology, presented in a problem-based way. The topics have been carefully chosen to cover the vast majority of situations likely to be encountered by the... more
A book of 50 or so of the most common presenting symptoms in obstetrics and gynaecology, presented in a problem-based way. The topics have been carefully chosen to cover the vast majority of situations likely to be encountered by the undergraduate-and most importantly-those on which they will be examined. Each topic is introduced by a short case vignette. This is followed by a description of the appropriate clinical examination, diagnostic procedures, treatment and prognosis. It will complement more traditionally organised textbooks, ...
Research Interests:
Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal... more
Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large-for-gestational-age infants. Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large-for-gestational-age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self-reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity....
Research Interests:
Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal... more
Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large-for-gestational-age infants. Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large-for-gestational-age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self-reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity....
Research Interests:
Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP.... more
Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP. Several lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population. This was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study. A total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study v...
Research Interests:
Turnbull and colleagues 1 provide clear evidence that a small group of midwives managing women throughout pregnancy offer major improvements in patient satisfaction as well as marginal clinical benefit. The transfer rate of a third of... more
Turnbull and colleagues 1 provide clear evidence that a small group of midwives managing women throughout pregnancy offer major improvements in patient satisfaction as well as marginal clinical benefit. The transfer rate of a third of women in this study is very important, even in a group selected at recruitment as being at low risk, and is similar to other groups offered midwife care in a teaching hospital 2 and that described in an unselected group in whom intermediate care was provided by general...
Research Interests:
Research Interests:
Research Interests:
Forty-nine obstetricians from three European countries were asked when they would advise delivery for a preterm fetus failing to thrive in utero, given various gestational ages, and a range of either umbilical artery Doppler flow velocity... more
Forty-nine obstetricians from three European countries were asked when they would advise delivery for a preterm fetus failing to thrive in utero, given various gestational ages, and a range of either umbilical artery Doppler flow velocity waveforms or CTG variability measures. Their responses indicated a wide area of disagreement about the correct timing of delivery, and a willingness to randomize patients to clinical trials of management. The area of uncertainty corresponded to the gestational age and Doppler bands at which participants have been entered to the pilot phase of a randomised trial of timed delivery, the Growth Restriction Intervention Trial (GRIT).
Research Interests:
Roberts J. Jenkins C, Wilson R, Pearson C, Franklin IA, MacLean MA, McKillop JH, Walker JJ. Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies. Eur J... more
Roberts J. Jenkins C, Wilson R, Pearson C, Franklin IA, MacLean MA, McKillop JH, Walker JJ. Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies. Eur J Endocrinol 1996;134:84–6. ISSN 0804–4643 The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pr...
Research Interests:
Research Interests: Cryobiology, Chemistry, Kinetics, Cryopreservation, Magnetic Resonance Spectroscopy, and 13 moreMedicine, Humans, Glutathione, Rs, Medical Physiology, Second Order, Glutathione Reductase, Oxidation-Reduction, Biochemistry and cell biology, Spin Echo, Rate Constant, kinetic analysis, and In Vitro Techniques
Research Interests:
Research Interests:
Research Interests:
Research Interests:
To investigate linkage between the renin gene restriction fragment length polymorphisms in families with a history of preeclampsia/eclampsia. Nine Icelandic families with at least three affected females in two or three generations were... more
To investigate linkage between the renin gene restriction fragment length polymorphisms in families with a history of preeclampsia/eclampsia. Nine Icelandic families with at least three affected females in two or three generations were investigated. DNA from lymphocytes was digested with the endonuclease restriction enzyme Bgl I and restriction fragments were transferred by Southern Blotting. Hybridisation was effected with the 32P-oligonucleotide-labeled diallelic genomic probe pHRnX 0.8. LOD scores were calculated by the Liped program for two forms of inheritance patterns. Affected sib pairs were analysed. Frequencies of the 9.0 kb and 5.0 kb alleles were 0.67 and 0.33, with no significant differences between affected females and spouses and combined LOD scores of -2 for recombination values of 3%. Allele sharing in affected sibs was not different from the expected random assortment. The linkage analysis provides evidence to exclude alteration of the renin gene in pregnancy as being directly responsible for the manifestations of preeclampsia or eclampsia in these families.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Risk assessment, Adolescent, British medical history, Pregnancy, Humans, and 13 moreHuman Resources for Health, Female, Community health nursing, Day Care, Adult, Public health systems and services research, BMJ, Risk Assessment, Early Diagnosis, Prenatal Care, Pre Eclampsia, Health Resources, and Referral and consultation
Fetal anaemia may arise from haemolysis or failure of production of red blood cells (RBC). Management has included use of previous history, antibody levels (in isoimmunised pregnancies) and amniocentesis for spectrophotometric examination... more
Fetal anaemia may arise from haemolysis or failure of production of red blood cells (RBC). Management has included use of previous history, antibody levels (in isoimmunised pregnancies) and amniocentesis for spectrophotometric examination of liquor. This is an invasive procedure with risk of adverse outcome and little efficacy when anaemia is due to decreased RBC production. Recently, Doppler velocimetry as a noninvasive method to detect fetal anaemia has been advocated with increased peak systolic velocity (PSV) in ...
Research Interests:
To develop a prediction model for term infants born large for gestational age (LGA) by customised birthweight centiles. International prospective cohort of nulliparous women with singleton pregnancy recruited to the Screening for... more
To develop a prediction model for term infants born large for gestational age (LGA) by customised birthweight centiles. International prospective cohort of nulliparous women with singleton pregnancy recruited to the Screening for Pregnancy Endpoints (SCOPE) study. LGA was defined as birthweight above the 90th customised centile, including adjustment for parity, ethnicity, maternal height and weight, fetal gender and gestational age. Clinical risk factors, ultrasound parameters and biomarkers at 14-16 or 19-21 weeks were combined into a prediction model for LGA infants at term using stepwise logistic regression in a training dataset. Prediction performance was assessed in a validation dataset using area under the Receiver Operating Characteristics curve (AUC) and detection rate at fixed false positive rates. The prevalence of LGA at term was 8.8% (n = 491/5628). Clinical and ultrasound factors selected in the prediction model for LGA infants were maternal birthweight, gestational wei...
Research Interests:
BackgroundThere is little evidence for modifiable factors for normal pregnancy. Most work has focused on prediction of complicated pregnancy.MethodsData from 3513 healthy nulliparous women with a singleton pregnancy participating in the... more
BackgroundThere is little evidence for modifiable factors for normal pregnancy. Most work has focused on prediction of complicated pregnancy.MethodsData from 3513 healthy nulliparous women with a singleton pregnancy participating in the SCreening fOr Pregnancy Endpoints study from six centers in New Zealand (Auckland), Australia (Adelaide), UK (London, Manchester, Leeds) and Ireland (Cork) were analysed using logistic regression to identify risk
Research Interests:
Care for the drug-using pregnant woman is being increasingly recognized as part of the obstetrician&#39;s role. There is great potential for improvement in provision of services for this group of women, partly because traditionally... more
Care for the drug-using pregnant woman is being increasingly recognized as part of the obstetrician&#39;s role. There is great potential for improvement in provision of services for this group of women, partly because traditionally our antenatal clinics have not been perceived as being conducive to disclosure regarding drug use, but also because hard data and, indeed, randomized controlled trials on the subject, are scarce.From the little evidence available, and from our own experience in this area, we have attempted to outline the main problems encountered in the antenatal, intrapartum and postnatal periods with each of the main drugs of abuse and the management thereof. It is important to note that we include cigarette smoking and alcohol, probably the most commonly used drugs in pregnancy, and recognize that the picture is wider than the stereotypical emaciated intravenous heroin addict. Where possible, evidence from trial data is included, but much of the what is quoted is descriptive from personal experience from ourselves and others working in the field.
Research Interests:
Abstract Introduction In women at risk of midtrimester loss or extreme preterm birth (PTB), insertion of a cervical cerclage has been shown to reduce that risk. 1 Three common techniques are used. We present the findings of an audit on... more
Abstract Introduction In women at risk of midtrimester loss or extreme preterm birth (PTB), insertion of a cervical cerclage has been shown to reduce that risk. 1 Three common techniques are used. We present the findings of an audit on our results following insertion of McDonald, Shirodkar and Transabdominal cervicoisthmic sutures. Methods Retrospective data were collected from the Leeds Teaching Hospitals maternity database on 178 women who had had a cervical suture over the past 5 years. Success was defined as the ...
Research Interests:
nature.com homepage Login. Nature Genetics homepage: My account; E-alert sign up. Register; Subscribe. Publications AZ index; Browse by subject. Search Advanced search. Advertisement. Journal home &amp;amp;amp;amp;amp;amp;amp;amp;gt;... more
nature.com homepage Login. Nature Genetics homepage: My account; E-alert sign up. Register; Subscribe. Publications AZ index; Browse by subject. Search Advanced search. Advertisement. Journal home &amp;amp;amp;amp;amp;amp;amp;amp;gt; Archive &amp;amp;amp;amp;amp;amp;amp;amp;gt; Table of Contents &amp;amp;amp;amp;amp;amp;amp;amp;gt; Correspondence &amp;amp;amp;amp;amp;amp;amp;amp;gt; References. Journal home, Advance online publication, Current issue, Archive, Press releases, Free Association (blog), Supplements, Focuses, Guide to authors, Online submission. For referees, Free online issue, Contact the journal, Subscribe, Advertising, work@npg, Reprints and permissions, About ...
Research Interests:
Research Interests:
Research Interests:
Murine pregnancy is characterised by marked increases in serum cytokine profiles with advancing gestation, but whether these changes reflect concentrations in amniotic fluid is unknown. This study therefore profiled 23 cytokines by... more
Murine pregnancy is characterised by marked increases in serum cytokine profiles with advancing gestation, but whether these changes reflect concentrations in amniotic fluid is unknown. This study therefore profiled 23 cytokines by fluid-phase multiplex immunoassay of amniotic fluid and serum collected from naturally mated mice during mid- and late pregnancy (days 11 and 18, respectively). The marked increase in serum profile of many cytokines from days 11 to 18 was not reflected in amniotic fluid, wherein most cytokine concentrations were lower on day 18. Serum and amniotic fluid cytokine concentrations were largely inversely related, indicating separate, localised regulatory mechanisms geared towards the maintenance of pregnancy, modulation of immune effector cell function and optimisation of fetal development. We suggest that, while maternal systemic inflammatory priming prepares the mother for birth, the amniotic compartment exhibits a tightly regulated inflammatory quiescence. These findings are discussed in relation to the onset of labour, which ultimately results in the elevated cytokine amniotic levels traditionally associated with the final stages of pregnancy.
Research Interests:
The relationship between maternal peripheral plasma concentrations of prostaglandin E2 and prostaglandin F2 alpha metabolites (bicyclo-PGEM and PGFM respectively) and the level of uterine activity in spontaneous labour was studied in 10... more
The relationship between maternal peripheral plasma concentrations of prostaglandin E2 and prostaglandin F2 alpha metabolites (bicyclo-PGEM and PGFM respectively) and the level of uterine activity in spontaneous labour was studied in 10 nulliparous and 10 multiparous women. Plasma prostaglandin metabolites were measured by radioimmunoassay. Uterine activity was quantified by computer analysis of changes in intrauterine pressure and expressed as mean active pressure (MAP). As labour progressed, both parity groups showed a significant rise in MAP which was associated with a significant increase in the levels of PGFM. However, the percentage rise in PGFM did not significantly correlate with the percentage rise in MAP. At all stages in labour PGFM and MAP levels were higher in the nulliparous group compared with the multiparous group. Bicyclo-PGEM levels showed no significant change in the nulliparous group but rose in late first stage/second stage in the multiparous group. Our observations support a role for prostaglandin F2 alpha in the generation of uterine activity in spontaneous labour. However, further study is required to elucidate the mechanisms controlling prostaglandin production by the fetal membranes and decidua in vivo, and how this relates to maternal peripheral plasma prostaglandin metabolite concentrations and the level of uterine activity.