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Biomedical subjects

C Greenwood

Publications and source records attributed to C Greenwood.

At least 19 recordsLinked to original sources
PubMed2006

Does a first trimester dating scan using crown rump length measurement reduce the rate of induction of labour for prolonged pregnancy? An uncompleted randomised controlled trial of 463 women.

OBJECTIVE: To evaluate the effect of a first trimester ultrasound dating scan on the rate of induction of labour for prolonged pregnancy. DESIGN: Randomised controlled trial to include 400 women in each arm of the trial. SETTING: Participating general practices and a district general teaching hospital. POPULATION: Women attending their general practitioner in the first trimester to confirm pregnancy, in whom a first trimester ultrasound scan was not indicated. METHODS: Women randomised to the study group (scan group) underwent an ultrasound dating scan between 8 and 12 weeks, measuring crown-rump length. The estimated date of delivery (EDD) was changed if there was a discrepancy of more than 5 days from the gestation, calculated from the last menstrual period (LMP). For the remaining women (no-scan group), gestation was determined using the LMP. MAIN OUTCOME MEASURES: The rate of induction of labour for prolonged pregnancy. RESULTS: Due to circumstances beyond the researchers' control, recruitment was abandoned when 463 women had been enrolled. The EDD was adjusted in 13 (5.7%) women in the scan group and in 2 (0.9%) in the no-scan group. There was no difference in the rate of induction for prolonged pregnancy between the scan (19 [8.2%]) and the no-scan (17 [7.4%]) groups (relative risk 1.10; 95% CI 0.59-2.07). CONCLUSIONS: Acknowledging the reduced numbers recruited for study, it is concluded that there is no evidence that a first trimester ultrasound dating scan reduces the rate of induction of labour for prolonged pregnancy and may result in a more expensive healthcare strategy.

Adult↗
PubMed2005

Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

OBJECTIVE: To investigate risk factors for cerebral palsy in relation to gestational age. DESIGN: Three case-control studies within a geographically defined cohort. SETTING: The former Oxfordshire Health Authority. PARTICIPANTS: A total of 235 singleton children with cerebral palsy not of postnatal origin, born between 1984 and 1993, identified from the Oxford Register of Early Childhood Impairment; 646 controls matched for gestation in three bands: or=37 weeks. RESULTS: Markers of intrapartum hypoxia and infection were associated with an increased risk of cerebral palsy in term and preterm infants. The odds ratio (OR) for hypoxia was 12.2 (95% confidence interval 1.2 to 119) at or=37 weeks. Corresponding ORs for neonatal sepsis were 3.1 (1.8 to 5.4) and 10.6 (2.1 to 51.9). In contrast, pre-eclampsia carried an increased risk of cerebral palsy at >or=37 weeks (OR 5.1 (2.2 to 12.0)) but a decreased risk at <or=32 weeks (OR 0.4 (0.2 to 1.0)). However, all infants <or=32 weeks with maternal pre-eclampsia were delivered electively, and their risk of cerebral palsy was no lower than that of other electively delivered <or=32 week infants (OR 0.9 (0.3 to 2.7)). Nearly 60% of <or=32 week controls were delivered after spontaneous preterm labour, itself an abnormal event. CONCLUSION: Inflammatory processes, including pre-eclampsia, are important in the aetiology of cerebral palsy. The apparent reduced risk of cerebral palsy associated with pre-eclampsia in very preterm infants is driven by the characteristics of the gestation matched control group. Use of the term "protective" in this context should be abandoned.

Biomarkers↗
PubMed2001

Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial.

OBJECTIVE: To compare the effectiveness and safety of low-dose unfractionated heparin and a low-molecular-weight heparin as prophylaxis against venous thromboembolism after colorectal surgery. METHODS: In a multicenter, double-blind trial, patients undergoing resection of part or all of the colon or rectum were randomized to receive, by subcutaneous injection, either calcium heparin 5,000 units every 8 hours or enoxaparin 40 mg once daily (plus two additional saline injections). Deep vein thrombosis was assessed by routine bilateral contrast venography performed between postoperative day 5 and 9, or earlier if clinically suspected. RESULTS: Nine hundred thirty-six randomized patients completed the protocol and had an adequate outcome assessment. The venous thromboembolism rates were the same in both groups. There were no deaths from pulmonary embolism or bleeding complications. Although the proportion of all bleeding events in the enoxaparin group was significantly greater than in the low-dose heparin group, the rates of major bleeding and reoperation for bleeding were not significantly different. CONCLUSIONS: Both heparin 5,000 units subcutaneously every 8 hours and enoxaparin 40 mg subcutaneously once daily provide highly effective and safe prophylaxis for patients undergoing colorectal surgery. However, given the current differences in cost, prophylaxis with low-dose heparin remains the preferred method at present.

Anticoagulants↗
PubMed2001

Fever in labour and neonatal encephalopathy: a prospective cohort study.

OBJECTIVE: To determine whether the reported association of maternal fever with neonatal encephalopathy is independent of other associated intrapartum risk factors. DESIGN: Prospective cohort study. SETTING: Dublin teaching hospital delivery ward. POPULATION: 4,915 low risk women in labour at 36-41 weeks of gestation. METHODS: Using logistic regression with odds ratios and 95% confidence intervals, the incidence of neonatal encephalopathy and other neonatal outcomes of women who had an intrapartum fever >37.5 degrees C was compared with those who did not. RESULTS: The cohort comprised 33% of all deliveries during the study period. Neonatal encephalopathy was diagnosed in 3.25/1,000 births. The incidence of intrapartum fever was 6.8%. Maternal fever was strongly associated with neonatal encephalopathy (crude OR 10.8, 95% CI 4.0-29.3). Univariate analysis showed maternal fever was associated with epidural analgesia, nulliparity, induction, longer labour, oxytocin administration, greater fetal birthweight and gestational age and instrumental vaginal delivery, but not with prolonged (>24hours) prelabour rupture of the membranes. The association of fever with neonatal encephalopathy persisted having adjusting for these covariates (adjusted OR 4.72, 95% CI 1.28-17.4). CONCLUSIONS: The relationship between maternal intrapartum fever and neonatal encephalopathy is independent of other known intrapartum risk factors. This provides further evidence for the role of inflammatory processes in the aetiology of neonatal neurological morbidity.

Brain Diseases↗
PubMed2001

The relation between pre-eclampsia at term and neonatal encephalopathy.

OBJECTIVES: To determine whether pre-eclampsia, hypothesised to be an inflammatory condition, is associated with fever in term labour, and confirm and examine the reported association of pre-eclampsia at term with neonatal encephalopathy. DESIGN: Prospective cohort study. SETTING: A Dublin teaching hospital. PARTICIPANTS: 6163 women in labour with singleton pregnancies at term at low risk for intrapartum hypoxia, recruited to a randomised trial examining the effect of admission cardiotocography on neonatal outcome. RESULTS: Pre-eclampsia was associated with maternal fever > 37.5 degrees in labour (odds ratio (OR) 3.39, 95% confidence interval (CI) 2.1 to 5.4); this was independent of obstetric intervention (adjusted OR 2.07, 95% CI 1.24 to 3.47). Pre-eclampsia was associated with neonatal encephalopathy (OR 25.5, 95% CI 8.4 to 74.7); this too was independent of obstetric intervention (adjusted OR 18.5, 95% CI 5.9 to 58.1). Cord arterial pH values were significantly lower in pre-eclamptics (7.20 v 7.24), although severe cord acidaemia was not significantly more common (OR 2.91, 95% CI 0.7 to 9.9). The association of pre-eclampsia with encephalopathy was independent of maternal fever (adjusted OR 16.5, 95% CI 5.1 to 54) and cord acidaemia (adjusted OR 13.5, 95% CI 3.2 to 56.7). CONCLUSIONS: The association of pre-eclampsia with maternal fever at term supports the hypothesis that pre-eclampsia is an inflammatory condition. The association of pre-eclampsia with neonatal encephalopathy is independent of obstetric intervention and cannot be explained by either acidaemia or maternal fever. A systemic inflammatory response in the fetus, perhaps secondary to oxidative stress, could explain the link between maternal pre-eclampsia and neonatal encephalopathy, and this may occur through cerebral vasoconstriction.

Blood Gas Analysis↗
PubMed2000

Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection.

BACKGROUND AND OBJECTIVES: Allogeneic red blood cell transfusions may exert immunomodulatory effects in recipients including an increased rate of postoperative bacterial infection. It is controversial whether allogeneic transfusion is an independent predictor for the development of postoperative bacterial infection. METHODS: We analysed a prospectively collected database of 1,349 patients undergoing colorectal surgery in 11 centres across Canada. The primary outcome was the development of either a postoperative wound infection or intra-abdominal sepsis in transfused and nontransfused patients. The effect of allogeneic transfusion on postoperative infection was evaluated with adjustment for all the confounding factors in a multiple regression analysis. RESULTS: The 282 patients who received a total of 832 allogeneic units had a significantly higher frequency of wound infections and intra-abdominal sepsis than the patients who were not transfused (25. 9 vs. 14.2%, p = 0.001). A significant dose-response relationship between transfusion and infection rate was demonstrated. Multiple regression analysis identified allogeneic transfusion as a statistically significant independent predictor for postoperative bacterial infection (OR 1.18, 95% CI 1.05-1.33, p = 0.007). Other independent predictors were anastomotic leak, repeat operation, patient age and preoperative haemoglobin level. The mortality rate was also significantly higher in the transfused group. CONCLUSION: These data support the hypothesis that allogeneic red cell transfusion is an independent risk factor for the development of postoperative bacterial infection in patients undergoing colorectal surgery. This association provides further reason to minimise exposure to allogeneic transfusions in the perioperative setting.

Abdomen↗
PubMed1999

Electron transfer kinetics of caa3 oxidase from Bacillus stearothermophilus: a hypothesis for thermophilicity.

The O2 reaction and the reverse electron transfer of the thermophilic caa3 terminal oxidase of Bacillus stearothermophilus have been studied by laser flash-photolysis. The results show that both reactions, although studied at a temperature of 20 degreesC, far from the optimal temperature of > 60 degreesC for caa3, follow a kinetic behavior essentially identical to that observed with the electrostatic complex between mammalian cyt c and cyt c oxidase. In the O2 reaction cyt a and cyt a3 are very quickly oxidized; cyt a is then re-reduced via CuA, whereas cyt c oxidation is apparently rate-limited by the oxidation of CuA. Upon photodissociation of the mixed valence-CO caa3, reverse electron transfer from the binuclear center to cyt a3+ (tau1 = 3 micros) and CuA2+ (tau2 = 64 micros) is observed, while cyt c is not reduced by any detectable level. These results seem to rule out accounting for enzymatic thermophilicity by altered kinetics of intramolecular electron transfer involving the cyt center in the reduced configuration, which is very fast. On the basis of these results and previous data, we propose that thermophilicity involves an increased activation barrier for the reduction of cyt a3-CuB in the configuration typical of the oxidized site.

Biophysical Phenomena↗
PubMed1998

The dinuclear center of cytochrome bo3 from Escherichia coli.

For the study of the dinuclear center of heme-copper oxidases cytochrome bo3 from Escherichia coli offers several advantages over the extensively characterized bovine cytochrome c oxidase. The availability of strains with enhanced levels of expression allows purification of the significant amounts of enzyme required for detailed spectroscopic studies. Cytochrome bo3 is readily prepared as the fast form, with a homogeneous dinuclear center which gives rise to characteristic broad EPR signals not seen in CcO. The absence of CuA and the incorporation of protohemes allows for a detailed interpretation of the MCD spectra arising from the dinuclear center heme o3. Careful analysis allows us to distinguish between small molecules that bind to heme o3, those which are ligands of CuB, and those which react to yield higher oxidation states of heme o3. Here we review results from our studies of the reactions of fast cytochrome bo3 with formate, fluoride, chloride, azide, cyanide, NO, and H2O2.

Animals↗
PubMed1997

Fast cytochrome bo from Escherichia coli binds two molecules of nitric oxide at CuB.

The reaction of nitric oxide (NO) with fast cytochrome bo from Escherichia coli has been studied by electronic absorption, MCD, and EPR spectroscopy. Titration of the enzyme with NO showed the formation of two distinct species, consistent with NO binding stoichiometries of 1:1 and 2:1 with observed dissociation constants at pH 7.5 of approximately 2.3 x 10(-)6 and 3.3 x 10(-)5 M. Monitoring the titration by EPR spectroscopy revealed that the broad EPR signals at g approximately 7.3, 3.7, and 2.8 due to magnetic interaction between high-spin heme o (S = 5/2) and CuBII (S = 1/2) are lost. A high-spin heme o signal at g = 6.0 appears as the 1:1 complex is formed but is lost again on formation of the 2:1 complex, which is EPR silent. The absorption spectrum shows that heme o remains in the high-spin FeIII state throughout the titration. These results are consistent with the binding of up to two NO molecules at CuBII. This has been confirmed by studies with the Cl- adduct of fast cytochrome bo. MCD evidence shows that heme o remains ligated by histidine and water. Addition of excess NO to the Cl- adduct leads to the appearance of a high-spin FeIII heme EPR signal. Hence chloride ion binds to CuB, blocking the binding of a second NO molecule. These results suggest a mechanism for the reduction of NO to nitrous oxide by cytochrome bo and cytochrome c oxidase in which the binding of two cis NO molecules at CuB permits the formation of an N-N bond and the abstraction of oxygen by the heme group.

Bacterial Proteins↗
PubMed1997

A conserved glutamic acid in helix VI of cytochrome bo3 influences a key step in oxygen reduction.

We have compared the reactions with dioxygen of wild-type cytochrome bo3 and a mutant in which a conserved glutamic acid at position-286 of subunit I has been changed to an alanine. Flow-flash experiments reveal that oxygen binding and the rate of heme-heme electron transfer are unaffected by the mutation. Reaction of the fully (3-electron) reduced mutant cytochrome bo3 with dioxygen yields a binuclear center which is substantially in the P (peroxy) state, not the well-characterized F (oxyferryl) state which is the product of the reaction of the fully reduced wild-type enzyme with dioxygen [Puustinen, A., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 1545-1548]. These results confirm that proton uptake is important in controlling the later stages of dioxygen reduction in heme-copper oxidases and show that E286 is an important component of the channel that delivers these protons to the active site.

Amino Acid Sequence↗
PubMed1997

A two-state analysis of co-operative oxygen binding in the three human embryonic haemoglobins.

The binding of oxygen to the three human embryonic haemoglobins, at pH 7.4, has been shown to occur as a co-operative process. Analysis of oxygen-binding curves obtained in the absence of organic phosphate allosteric effectors shows that the process can be described quite accurately by the two-state model of allosteric action. In the presence of organic phosphates, the binding affinity for oxygen to the T-state of the alpha 2 epsilon 2 and zeta 2 epsilon 2 haemoglobins is significantly lowered. The values of the best-fit two-state parameters determined for each of the embryonic haemoglobins together with the temperature-dependence of the overall equilibrium binding process are discussed in terms of oxygen transfer from the maternal blood supply. Fast-reaction studies have been used to determine the rate constants of the oxygen association and dissociation processes occurring in the R-state and the rate of the allosteric R > T conformational transition. Analysis of these data suggests a likely reason for the high affinity and low co-operativity of the embryonic proteins and identifies the origins of the inability of equilibrium measurements to identify chain non-equivalence in the R-state.

Allosteric Regulation↗
PubMed1997

Reaction of variant sperm-whale myoglobins with hydrogen peroxide: the effects of mutating a histidine residue in the haem distal pocket.

The reaction of hydrogen peroxide with a number of variants of sperm-whale myoglobin in which the distal pocket histidine residue (His64) had been mutated was studied with a combination of stopped-flow spectroscopy and freeze-quench EPR. The rate of the initial bimolecular reaction with hydrogen peroxide in all the proteins studied was found to depend on the polarity of the amino acid side chain at position 64. In wild-type myoglobin there were no significant optical changes subsequent to this reaction, suggesting the rapid formation of the well-characterized oxyferryl species. This conclusion was supported by freeze-quench EPR data, which were consistent with the pattern of reactivity previously reported [King and Winfield (1963) J. Biol. Chem. 238, 1520-1528]. In those myoglobins bearing a mutation at position 64, the initial bimolecular reaction with hydrogen peroxide yielded an intermediate species that subsequently decayed via a second hydrogen peroxide-dependent step leading to modification or destruction of the haem. In the mutant His64-->Gln the calculated electronic absorption spectrum of the intermediate was not that of an oxyferryl species but seemed to be that of a low-spin ferric haem. Freeze-quench EPR studies of this mutant and the apolar mutant (His64-->Val) revealed the accumulation of a novel intermediate after the first hydrogen peroxide-dependent reaction. The unusual EPR characteristics of this species are provisionally assigned to a low-spin ferric haem with bound peroxide as the distal ligand. These results are interpreted in terms of a reaction scheme in which the polarity of the distal pocket governs the rate of binding of hydrogen peroxide to the haem iron and the residue at position 64 governs both the rate of heterolytic oxygen scission and the stability of the oxyferryl product.

Amino Acid Sequence↗
PubMed1997

Mealtime difficulties in a home for the aged: not just dysphagia.

A mealtime screening tool was administered to 349 residents of a home for the aged to determine the prevalence of mealtime difficulties including, but not limited to, dysphagia. Mealtime difficulties, as assessed during a single meal observation of each resident, were documented in 87% of these individuals. Though 68% exhibited signs of dysphagia, 46% had poor oral intake, 35% had positioning problems, and 40% exhibited challenging behaviors. An increased prevalence of mealtime difficulties was related to both the presence and degree of cognitive impairment. Oral intake was best among residents with severe cognitive impairment, many of whom received partial to total feeding assistance. In contrast, poor oral intake was associated with mild-moderate cognitive impairment, pointing to a need for more aggressive intervention with this group. The results clearly demonstrate that the prevalence of a wide range of eating-related problems far exceeds accepted estimates of dysphagia alone and support a multidisciplinary approach to mealtime interventions for the institutionalized elderly. Additionally, the magnitude of problems identified has implications for both resource and staff-training requirements in long-term care facilities.

Aged↗