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Biomedical subjects

W Fraser

Publications and source records attributed to W Fraser.

At least 19 recordsLinked to original sources

Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX.

Patients with glycogen storage disease (GSD) types I, III and IX show reduced bone mineral content, but there is scarce data on new serum and urine markers of bone turnover or their relationship to bone densitometry. Six GSD I, four GSD III and four GSD IX patients underwent bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry. Free pyridinoline (fPYD):creatinine and free deoxypyridinoline (fDPD):creatinine ratios were analysed on random urines. Procollagen type I C-terminal propeptide, procollagen type I N-terminal propeptide (PINP), carboxyterminal telopeptide of type I collagen and bone-specific alkaline phosphatase were analysed in serum. Some GSD I and GSD III patients had low or very low BMD. There was no difference in total body BMD z-score between the GSD types after adjusting for height (p=0.110). Bone marker analysis showed no consistent pattern. Urine fPYD:creatinine ratio was raised in four GSD I and two GSD III patients, while serum PINP was inappropriately low in some of these patients. There was no clear correlation between any markers of bone destruction and total body z-score, but the patient with the lowest total body z-score showed the highest concentrations of both urinary fPYD:creatinine and fDPD:creatinine ratios. We conclude that some GSD I and GSD III patients have very low bone mineral density. There is no correlation between mineral density and bone markers in GSD patients. The inappropriately low concentration of PINP in association with the raised urinary fPYD:creatinine and fDPD:creatinine ratios seen in two GSD I patients reflect uncoupling of bone turnover. All these findings taken together suggest that some GSD I and GSD III patients may be at an increased risk of osteoporosis.

Absorptiometry, Photon↗

Epidemiology of the insulin-like growth factor system in three ethnic groups.

The insulin-like growth factor (IGF) system, comprising insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and their binding proteins (IGFBPs), is linked to cell growth, the development of cardiovascular disease, and several cancers. Little is known about its epidemiology. The authors studied relations of the IGF system to anthropometric and metabolic variables in three population-based ethnic groups in Manchester, England, in 1994-1998 with differing disease risks: African Caribbean (n = 193), Pakistani (n = 130), and local Europeans(n = 142). Standardized anthropometry, glucose tolerance tests, and serum assays were performed. Body mass indices (BMIs) were high in all groups. IGF-I levels were highest in normoglycemic African Caribbeans and declined with age (r = -0.28). IGF-II levels were greatest in Europeans. IGFBP-1 concentrations increased with age in Pakistanis (r = 0.20) and Europeans (r = 0.29), but not in African Caribbeans (r = 0.06), and were inversely related to BMI (r = -0.37). Age- and sex-adjusted IGFBP-1 was inversely related to fasting insulin and proinsulin in all groups; participants with newly detected diabetes were relatively insulinopenic but had higher IGFBP-1 concentrations. Nonesterified (free) fatty acid (NEFA) concentrations increased with declining glucose tolerance. In multiple regression analysis, IGFBP-1 was independently and negatively related to fasting insulin, BMI, and African-Caribbean compared with European ethnicity but positively related to age, fasting glucose, and NEFA. IGF-I was inversely related only to age, NEFA, and Pakistani ethnicity. IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples.

Adult↗

A randomized clinical trial of care for women with preterm labour: home management versus hospital management.

BACKGROUND: Preterm labour occurs in about 10% of all pregnancies and is the most important cause of premature birth. Women with preterm labour are admitted to hospital to have the contractions stopped. Thereafter, many women remain in hospital until delivery. We conducted a randomized clinical trial to compare hospital care with home care of women who had been admitted to hospital for preterm labour. METHODS: After they had received treatment for an acute episode of premature labour, women at 2 regional perinatal centres associated with teaching hospitals were randomly assigned to home care or hospital care. Eligible women (n = 250) were aged 18 years or older, lived within 50 km of the hospital, had a gestational age between 20 and 35 weeks, had no prior preterm delivery and were experiencing their first episode of preterm labour and first admission to hospital for preterm labour. Analysis was by intention to treat. RESULTS: There were no significant differences between the 2 groups in mean gestational age at delivery (home: 37.52 weeks, hospital: 37.50 weeks) or in mean birth weight (home: 2974 g, hospital: 3020 g). There were no significant differences between the 2 groups with respect to the proportions of babies born before term or the mean duration of neonatal hospital stay, neonatal intensive care unit stay and intermediate care nursery stay. The mean duration of the first stay in hospital for the women in the home group (3.8 days) was significantly shorter than the mean duration for women in the hospital group (6.1 days). In addition, the mean duration of all maternal stays in hospital was significantly shorter for the women in the home group (3.7 days) than in the hospital group (5.0 days). INTERPRETATION: Home care management is an efficient and acceptable alternative to hospital care for women experiencing preterm labour.

Adolescent↗

Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.

AIMS/HYPOTHESIS: Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus. METHODS: In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA). RESULTS: Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009) and logistic regression indicated a 40% reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease.

Blood Glucose↗

A controlled clinical trial of home care management versus hospital care management for preterm labour.

Prenatal hospitalisation has not been shown to reduce perinatal morbidity and mortality, yet it is still the treatment of choice for women who experience preterm labour. Home care management may be an alternative means of delivering safe, efficacious and care for these women. The objectives of this controlled clinical trial were to examine differences in neonate's gestational age and birthweight, and antenatal stress, social support satisfaction, and family functioning among pregnant women receiving home care and those receiving hospital care management. Pregnant women experiencing preterm labour (N=250) were randomly assigned to home care management (the experimental group [EG]) or hospital care management (the control group [CG]). A Perinatal Information Form was used to collect data on sociodemographic and pregnancy variables. The High-Risk Pregnancy Stress Scale, Brown's Social Behaviors Inventory, and the Family Assessment Measure III Dyadic Relationships Scale were administered to the women at randomisation (T1) and at 1-week (T2) and 2-weeks (T3) after randomisation. Gestational age and birthweight were similar in the two groups of neonates. Women in the EG reported that antenatal stress was significantly lower at T3 than at T1 and T2, while for those in the CG, antenatal stress was significantly lower at T3 than at T1, and significantly lower at T2 than at T1. Women in the EG were more satisfied with support from the male partner at T3 than women in the CG. There was no significant difference between the two groups in family functioning at T1, T2 and T3. These findings indicate that home care management is a safe and efficacious mode of health care delivery for women experiencing preterm labour.

Adult↗

Risks of induction of labour in uncomplicated term pregnancies.

Our objective was to evaluate the risks of maternal and perinatal morbidity associated with induction of labour in uncomplicated term pregnancies. We conducted a retrospective cohort study including 7,430 women, not referred from another institution, with a single baby in vertex presentation, and delivering between 38 and 40 weeks of pregnancy. Among these women, 3,546 were excluded for prelabour pregnancy complications. Relative risks (RR), adjusted for parity, were computed to compare 3,353 women who went into labour spontaneously with 531 women whose labour was induced. Induction of labour was found to be associated with a higher risk of caesarean section [RR = 2.4, 95% CI 1.8, 3.4]. Use of non-epidural [RR = 1.5, 95% CI 1.2, 1.8] and of epidural analgesia [RR = 1.4, 95% CI 1.1, 1.7] was more frequent after labour induction. Resuscitation [RR = 1.2, 95% CI 1.0, 1.5], admission to the intensive care unit [RR = 1.6, 95% CI 1.0, 2.4] and phototherapy [RR = 1.3, 95% CI 1.0, 1.6] were more frequent after induction of labour. Results were similar when controlling simultaneously for parity, maternal age, gestational age, year of delivery, birthweight and the physician in charge of delivery in a logistic regression analysis. The results of this study suggests that induction of labour is associated with a higher risk of caesarean section and of some perinatal adverse outcomes. Induction of labour should be reserved for cases where maternal and perinatal benefits outweigh the risk of these complications.

Adult↗

Reducing antipsychotic medication in people with a learning disability.

BACKGROUND: The use of antipsychotic drugs in people with learning disabilities is currently receiving intensified scrutiny and attempts are being made to reduce it. AIMS: A randomised controlled trial was designed to investigate factors influencing antipsychotic drug reduction among people with learning disabilities prescribed such medication for behavioural problems. METHOD: Thirty-six participants randomly allocated to the experimental group underwent four, monthly 25% drug reduction stages. There were no planned drug changes for the control group (n = 20). RESULTS: Twelve participants (33%) completed full withdrawal; a further seven (19%) achieved and maintained at least a 50% reduction. Drug reduction was associated with increased dyskinesia and higher activity engagement but not increased maladaptive behaviour. Some setting characteristics were associated with drug reinstatement. CONCLUSIONS: A substantial proportion of people with learning disability prescribed antipsychotic medications for behavioural purposes rather than for treating psychotic illness can have their drugs reduced or withdrawn.

Adult↗

[Multicenter randomized trial of amnioinfusion].

Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.

Amniotic Fluid↗

Sweeping of the membranes to prevent post-term pregnancy and to induce labour: a systematic review.

OBJECTIVE: To evaluate the effectiveness of sweeping of the membranes to prevent post-term pregnancy and to induce labour. DESIGN: A systematic review of randomised controlled trials. METHODS: Potentially eligible trials were identified in Medline and in the Cochrane Controlled Trials Register. Inclusion of studies and data extraction were performed by two reviewers working independently. Summary estimates of the effect of the intervention were computed as relative risks, risk differences and weighted mean differences. MAIN OUTCOME MEASURES: Use of formal methods of labour induction, delay before spontaneous onset of labour, prevention of post-term pregnancy, side effects, maternal and perinatal morbidity. RESULTS: Sixteen reports were identified. Thirteen were included in the review, with a total of 1992 women. Sweeping of the membranes, when performed at term, reduced the duration of pregnancy and the proportion of women continuing pregnancy beyond 41 and 42 weeks. When sweeping of the membranes was performed, a reduction in the use of formal methods for labour induction was observed (RR = 0.48; 95% CI 0.28-0.85). There was no difference between groups in the mode of delivery or in the risk of infection. Discomfort during vaginal examination and other side effects (e.g. bleeding, irregular contractions) were more frequently reported by women allocated to sweeping. CONCLUSIONS: While sweeping of the membranes reduces the interval to spontaneous onset of labour, there is no evidence of a reduction in maternal or neonatal morbidity. When used as a means of induction of labour, the reduction in the use of formal methods must be balanced against women's discomfort and other side effects attributable to the procedure.

Extraembryonic Membranes↗

Expression of functional major histocompatibility complex class II molecules on HMC-1 human mast cells.

Mast cells hold a key position in the defensive mechanisms against exogenous intruders. In this study, we investigated whether human mast cells express functional major histocompatibility complex (MHC) class II molecules that can transduce endogenous signals and present staphylococcal enterotoxin A (SEA) to T cells. Similar to HMC-1 human mast cell line, umbilical cord blood-derived mast cells express HLA-DR, -DP and -DQ molecules on their surface. MHC class II molecules expressed on HMC-1 cells bind significantly the SEA (a natural MHC class II ligand), and their ligation with specific mAbs or with SEA, leads ultrastructural changes, suggesting their degranulation. Recognition of SEA-bound MHC class II molecules on HMC-1 mast cells by the T cell receptor of K25 cells, an SEA-specific murine T cell hybridoma, triggers significant IL-2 secretion by these T cell hybridomas. Hence, our data point out the expression of functional MHC class II molecules on human mast cells, reinforcing the implication of these cells in the defense mechanisms of acquired immunity.

Animals↗

Effects of smoking cessation on maternal airway function and birth weight.

OBJECTIVE: To evaluate the effects of smoking cessation before or early in pregnancy on maternal airway function and birth weight. METHODS: Measurements of forced expiratory spirometry including forced vital capacity, forced expiratory volume in 1 second, forced expiratory flow rates between 0.2 and 1.2 L, 25% and 75%, and 75% and 85%, and instantaneous flows at lung volumes of 25%, 50%, and 75% were carried out by a wedge bellow spirometer in 40 pregnant exsmokers and were compared with those of 175 nonsmoking and 97 currently smoking pregnant women. Spirometric testing was conducted at a mean (+/- SD) gestational age of 21.5 +/- 7.0 weeks. In exsmokers, the average lifetime cigarette consumption was 17.1 +/- 8.1/day for a mean duration of 9.7 +/- 3.9 years, similar to that observed in current smokers. The median duration of smoking abstinence was 20 weeks before study spirometry. RESULTS: All spirometric measurements in exsmokers were similar to those of nonsmokers and were significantly higher than those of current smokers. Spirometric measurements for nonsmokers, current smokers, and exsmokers were respectively: forced expiratory volume in 1 second (3.36 +/- 0.39, 3.09 +/- 0.45, and 3.35 +/- 0.32 L); forced expiratory flow rate between 25% and 75% (ie, mid-expiratory phase) (3.85 +/- 0.69, 3.21 +/- 0.76, and 3.86 +/- 0.66 L/sec); forced expiratory flow rate between 75% and 85% (ie end-expiratory phase) (1.39 +/- 0.35, 1.03 +/- 0.35, and 1.41 +/- 0.39 L/sec); instantaneous flow at lung volume of 50% (4.35 +/- 0.82, 3.76 +/- 0.89 and 4.36 +/- 0.68 L/sec); and instantaneous flow at lung volume of 25% (1.91 +/- 0.47, 1.47 +/- 0.49, and 1.92 +/- 0.46 L/sec). Mean gestational age at delivery was similar among the three groups (277 +/- 11,274 +/- 12, and 274 +/- 11 days for nonsmokers, current smokers, and exsmokers, respectively). The mean birth weight of babies born to exsmokers (3408 +/- 511 g) was similar to that of babies born to nonsmokers (3469 +/- 461 g), but was significantly greater than that of babies born to smoking pregnant women (3189 +/- 485 g; P < .001). CONCLUSION: Smoking cessation either before or at an early stage of pregnancy is associated with early, reversible increments of maternal airway function and mean birth weights that are higher than among women who continue smoking.

Adult↗

Effects of early augmentation of labour with amniotomy and oxytocin in nulliparous women: a meta-analysis.

OBJECTIVES: To estimate the effects among nulliparae of early augmentation with amniotomy and oxytocin on caesarean delivery, and on other indicators of maternal and neonatal morbidity including transfusion. Apgar score < 7 at 5 minutes, and admission to the special care nursery. DESIGN: Meta-analysis. METHODS: Published studies were identified through manual and computerised searches. Two unpublished studies were identified through direct communication with the investigators. Twelve trials were identified which compared a policy of early labour augmentation including amniotomy followed by oxytocin with a less active form of management. Two methodologically unacceptable studies were excluded. Studies were grouped according to whether they admitted only women with abnormal progress (therapy trials: n = 3) or accepted women with normal labour (prevention trials: n = 7). RESULTS: Unstratified analysis did not provide support for the hypothesis that early augmentation reduces the risk of caesarean section (typical odds ratio [OR] 0.9; 95% CI 0.7-1.1). The typical odds ratio for prevention trials was similar to that obtained in the unstratified analysis (typical OR 0.9, 95% CI 0.7-1.2). Although only a small number of women have been randomised in therapy trials, a trend toward a reduction in the rate of caesarean section with early intervention was seen in this group (typical OR 0.6, 95% CI 0.2-1.4). CONCLUSIONS: Early augmentation does not appear to provide benefit over a more conservative form of management in the context of care of nulliparous women with mild delays in the progress of labour. In the context of established delay in labour, an active policy of augmentation may reduce the risk of caesarean section. However, only three small trials have been performed in this context, and they do not have adequate power to allow firm conclusions to be drawn.

Amnion↗

Randomized controlled trial of a prenatal vaginal birth after cesarean section education and support program. Childbirth Alternatives Post-Cesarean Study Group.

OBJECTIVE: Our objective was to assess whether, for women with previous cesarean section, a prenatal education and support program promoting vaginal birth after cesarean delivery increases the probability of vaginal delivery. STUDY DESIGN: Women with a single previous cesarean were recruited before 28 weeks' gestation. Women's self-assessed motivation to attempt vaginal birth after a previous cesarean delivery was measured on a 10 cm visual analog scale: stratum I, low motivation; stratum II, high motivation. Women were randomized by stratum to one of two groups. Those in the "Verbal" group participated in an individualized education program. Those in the "Document" group were provided with a pamphlet detailing the benefits of planned vaginal birth after cesarean delivery. RESULTS: Rates of vaginal birth after cesarean section were similar in the verbal and document groups: verbal, 339 of 641 (53%); document, 310 of 634 (49%); relative risk 1.1, 95% confidence interval 1.0 to 1.2. There was no evidence of heterogeneity across motivational strata. Regardless of treatment group, women with low motivation for vaginal birth after cesarean section were more than three times as likely to undergo elective repeat cesarean than were women with high motivation (47% vs 13%). CONCLUSIONS: There was no evidence that an individualized prenatal education and support program, when offered to all women with previous cesarean delivery, results in a clinically significant increase in the rate of vaginal birth after cesarean section.

Adult↗

Early amniotomy increases the frequency of fetal heart rate abnormalities. Amniotomy Study Group.

OBJECTIVE: To determine whether early amniotomy, when practised as an isolated intervention, increases the hourly rate of fetal heart rate record abnormalities. DESIGN: This is a secondary analysis of the results of a multicentre randomised trial of early versus late amniotomy in labour. SETTING: Secondary and tertiary level teaching hospitals. INTERVENTION: Early amniotomy versus an attempt to conserve the amniotic membranes. MAIN OUTCOME MEASURES: The hourly rates of early, mild variable, severe variable and late decelerations; caesarean section rates. RESULTS: Severe variable decelerations, when classified as categorical events (> or = 1/h to 2/h, > or = 2/h to < 4/h, > or = 4/h), were more frequent in the amniotomy group (chi2 for trend = 5.7, P = 0.017). The mean hourly rates of severe variable and late fetal heart rate decelerations were increased in the amniotomy group (severe variable: amniotomy group 1.4/h, control 0.7/h, P = 0.021; late: amniotomy group 3.3/h, control 2.3/h, P = 0.011). Although the overall rate of caesarean was similar in the two groups (OR 1.2; 95% CI 0.8-1.8), there was an increase in caesarean section for fetal distress (OR 2.3; 95% CI 1.1-4.5) associated with amniotomy. CONCLUSION: Our data suggest that early amniotomy increases the hourly rate of severe variable fetal heart rate decelerations without evidence of an adverse effect on neonatal outcome. In settings where the diagnosis of fetal compromise is based primarily on electronic monitoring, caesarean section for fetal distress may be increased by early amniotomy.

Adult↗