Search Results - (Author, Cooperation:S. C. Robson)

2011-10-04

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Cell Line, Tumor ; Chromatin/genetics/*metabolism ; Chromatin Immunoprecipitation ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Heterocyclic Compounds with 4 or More Rings/pharmacology/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/genetics/*metabolism/pathology ; Mice ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism ; Myeloid-Lymphoid Leukemia Protein/*metabolism ; Oncogene Proteins, Fusion/*metabolism ; Protein Binding/drug effects ; Proteomics ; Transcription Factors/*antagonists & inhibitors/*metabolism ; Transcription, Genetic/drug effects

2013-12-20

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Alanine/genetics/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; Cell Nucleolus/metabolism ; Chromatin/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA, Ribosomal/genetics ; Epistasis, Genetic ; Glutamine/*metabolism ; Histones/*chemistry/*metabolism ; Humans ; Methylation ; Methyltransferases/metabolism ; Molecular Chaperones/metabolism ; Molecular Sequence Data ; Multiprotein Complexes/metabolism ; Nuclear Proteins/metabolism ; Nucleosomes/metabolism ; Protein Binding ; Protein Processing, Post-Translational ; RNA/metabolism ; RNA Polymerase I/*metabolism ; Ribonucleoproteins, Small Nucleolar/metabolism ; Saccharomyces cerevisiae/enzymology/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Substrate Specificity ; Transcription, Genetic

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Objective To audit the use of bolus hydralazine for control of severe hypertension within a protocol for the management of severe pre-eclampsia.Design A retrospective review.Setting Three UK teaching hospitals.Subjects Seventy consecutive women who received hydralazine for the treatment of sustained severe hypertension. Twenty-five women had more than one episode of hypertension amounting to a total of 109 treatment episodes.Intervention Intravenous bolus hydralazine 5 mg, repeated every 15min to reduce the mean arterial pressure to 〈 125 mmHg.Main outcome measures Change in mean arterial pressure in response to bolus hydralazine, fetal condition, as assessed by heart rate changes and umbilical arterial pH at delivery, and protocol violations were analysed.Results Mean arterial pressure fell by 12 mmHg (95% CI 10–14) after the first bolus, 9 mmHg (95% CI 6.5–12) after the second bolus and 5 mmHg (95% CI 1–10) after the third bolus. Eighty-two (75 %) episodes were managed strictly according to the protocol; of these, blood pressure was controlled by bolus therapy alone in 89%. Of the 27 instances in which the protocol was not adhered to, blood pressure was not controlled in four. There were no significant differences in the incidence of cardiotocographic abnormalities or umbilical acidaemia in the women treated before delivery (n= 36) compared with those in whom treatment was first initiated afterwards (n= 34).Conclusions Hydralazine given in 5 mg boluses is a safe and effective method of treating severe hypertension in pre-eclampsia. Despite clear management guidelines, protocol violations were common, and in 4% of treatment episodes these were potentially serious resulting in failure to control blood pressure.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Objective To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre-eclampsia and eclampsia.Design Prospective observational study comparing two phenytoin loading regimens.Setting Two UK teaching hospitals.Subjects Sixty-seven consecutive women with severe pre-eclampsia and five with eclampsia.Interventions The first 29 women were given a 15 mg/kg intravenous loading dose of phenytoin. The next 43 received 17.5 mg/kg. All were given 500 mg phenytoin 12 h after completion of the loading dose and then 250 mg every 12 h for four doses.Main outcome measures Total plasma phenytoin levels at 30 min, 6 h and 12 h after loading dose, 6 h after first maintenance dose and on days 2 and 3 of maintenance therapy; eclamptic seizures after starting phenytoin.Results Mean plasma phenytoin levels were higher at 30 min and 6 h after the 17.5 mg/kg loading dose. Nine of 29 (31%) phenytoin levels 30 min after the loading dose were above the therapeutic range in the 15 mg/kg group compared with 26/38 (68%) in the 17.5 mg/kg group (P〈0.01). Six of 27 (22%) phenytoin levels 12 h after the loading dose were subtherapeutic in the 15 mg/kg group compared with 2/38 (5%) in the 17.5 mg/kg group (P〈0.05). Three women, two in the 17.5 mg/kg group, developed seizures after starting phenytoin. All three had plasma levels within the therapeutic range.Conclusions Compared with a loading dose of 17.5 mg/kg, loading with 15 mg/kg phenytoin was associated with a lower incidence of high plasma levels at 30 min but a higher incidence of subtherapeutic levels at 12 h. Seizures occur in 2 to 3% of pre-eclamptics despite apparently therapeutic phenytoin levels.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Summary. Serial measurements of apparent liver blood flow and cardiac output were performed in 12 women at 12–14, 24–26 and 36–38 weeks of pregnancy and then at 10–12 weeks after delivery. Apparent liver blood flow was calculated from indocyanine green clearance. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. Postnatal apparent liver blood flow was 1.811/min and no significant change was demonstrated during pregnancy. In contrast cardiac output decreased from 7.461/min at 36–38 weeks gestation to 4.901/min after delivery. Apparent liver blood flow accounted for 24% of cardiac output during pregnancy. This increased to 37% after delivery.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Summary. Serial haemodynamic investigations were performed in 15 women at 38 weeks gestation and then 2, 6, 12 and 24 weeks after delivery. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic, pulmonary and mitral valves. Cardiac chamber size and ventricular function were investigated by M-mode echocardiography. Flow measurements at the three intracardiac sites correlated closely. Cardiac output fell from a mean of 7.421/min at 38 weeks to 4.961/min at 24 weeks after delivery, a fall of 33%. Most of this decrease (28%) had occurred by 2 weeks. This was associated with a 20% reduction in heart rate and an 18% reduction in stroke volume. By 2 weeks after delivery there was a significant decrease in left atrial dimension and left ventricular end-diastolic dimension. Left ventricular wall thickness and mass declined throughout the period of study as did aortic, pulmonary and mitral valve areas. M-mode derived indices of myocardial contractility were all significantly reduced by 2 weeks and thereafter showed no further change. No haemodynamic differences were found between lactating and non-lactating mothers.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Summary. Serial haemodynamic investigations were performed in 15 women delivered by elective caesarean section under epidural anaesthesia at 38–40 weeks gestation. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. No haemodynamic changes were demonstrable after attainment of surgical anaesthesia (T5 or above). Stroke volume increased 13% after delivery of the placenta and remained elevated until the end of the operation at which time cardiac output was 11% above pre-operative values. Stroke volume and cardiac output fell during the first postoperative day. Heart rate remained elevated at pre-operative values for 48 h after delivery. There was a fall in heart rate and cardiac output between the second and the sixth days after delivery. By 2 weeks after delivery cardiac output was 28% lower than pre-operative values. Compared with pre-operative values, diastolic blood pressure was lower on the first and second postnatal days.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Summary. A non-invasive technique for the measurement of cardiac output in pregnancy by combined cross-sectional and Doppler echocardiography at three intracardiac sites is described. The validity of the technique for use during pregnancy is reviewed. Comparison with cardiac output determined simultaneously by the direct Pick technique in 15 non-pregnant subjects showed close agreement for all three measurement sites. Acceptable measurements were obtained from the aortic and pulmonary valves in all pregnant subjects and from the mitral valve in 84% of pregnant subjects. The within-patient intra-observer and hour-to-hour variabilities of cardiac output in pregnant and non-pregnant subjects were 〈5% of the mean for all three valves studied. Flow measurements at each of the three intracardiac sites correlated closely. The advantages and limitations of the technique for use during pregnancy are discussed.

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Since the introduction of anti-Rhesus (Rh) D prophylaxis for RhD-negative women, other Rh and non-Rh red cell alloantibodies have become relatively more important and are now responsible for the greater proportion of haemolytic disease of the newborn. Anti-C and anti-E are the most commonly implicated non-D Rh antibodies in the pathogenesis of haemolytic disease of the newborn1. In 1977 Pepperell et al.2 reported the outcome of 44 women with anti-E. This is the only published series that investigates the implications of anti-E during pregnancy. The present report presents a retrospective study of the outcome of 122 pregnancies in which anti-E was the sole alloantibody detected.

Electronic Resource