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Biomedical subjects

R B Fraser

Publications and source records attributed to R B Fraser.

At least 19 recordsLinked to original sources
PubMed2006

Fetal size and growth velocity in the prediction of the large for gestational age (LGA) infant in a glucose impaired population.

OBJECTIVES: To evaluate the performances of estimated fetal weight (EFW) and fetal growth velocity (FGV) in the prediction of birth weight>95th centile amongst women with impaired glucose tolerance (IGT); the prediction of neonatal hypoglycaemia was a secondary endpoint. STUDY DESIGN: Two hundred and forty-two consecutive women (61 type 1 diabetes mellitus, 14 type 2 diabetes mellitus, 49 gestational diabetics and 118 with impaired glucose tolerance) receiving routine care at the combined diabetes/antenatal clinic, Jessop Hospital for Women, Sheffield. EFW was routinely calculated at approximately two-week intervals in the third trimester with the last EFW prior to delivery used in the analysis. FGV was calculated from two estimates of fetal weight between 21 and 35 days apart. EFW and FGV were both expressed as standard deviation (Z) scores. RESULTS: The mean gestational age at delivery was 37 weeks (range 26-40 weeks). Sixty-five (27%) infants were of birth weight>95th centile. Mean EFW Z scores were 2.7 and 0.99 for >95th and <95th centile, respectively (p<0.001). Receiver operator characteristics (ROC) curve analysis gave area under the curve 0.8; using a cut-off Z score of 1.7 (=95.5 centile), EFW has sensitivity 80% and specificity 72% in predicting an LGA neonate (likelihood ratios 2.8 and 0.27 for positive and negative test). Mean FGV Z scores were 0.85 and 0.4 for >95th and <95th centile, respectively (p>0.05); ROC curve analysis indicated no discriminatory capacity. Estimates of fetal size and growth performed poorly in the prediction of neonatal hypoglycaemia. CONCLUSION: In routine clinical practice, EFW has limited utility in the prediction of the LGA infant. FGV does not identify the LGA infant. EFW and FGV do not predict neonatal hypoglycaemia.

Anthropometry↗
PubMed2003

Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

Adult↗
PubMed2000

A longitudinal study of maternal anthropometric changes in normal weight, overweight and obese women during pregnancy and postpartum.

Many women associate one or more of their pregnancies with the development of adult obesity. Such an association has not been fully explored. This longitudinal study examines the changes in maternal anthropometric indices during pregnancy and postpartum. Seventy-seven pregnant subjects were investigated longitudinally at about 13, 25 and 36 weeks gestation, of whom forty-seven continued taking part into the postpartum period. Maternal weight, height and skinfold thickness (triceps, biceps, subscapular, suprailiac and mid thigh) were measured at each visit. Maternal fat mass was estimated from the conversion of the first four skinfold thicknesses. Maternal waist and hip circumferences were also measured at the first visit and 6 weeks and 6 months postpartum. Weight and fat gain during pregnancy (13-36 weeks gestation) was 10.9 (SD 4.7) kg and 4.6 (SD 3.3) kg (P < 0.001) respectively. A significant increase in fat mass from 13 weeks gestation to 6-months postpartum was observed (2.6 (SD 4.5), P < 0.001). The increased weight at 6-months postpartum, however, was not statistically significant (1.1 (SD 6.0) kg, P = 0.20). Based on BMI in early pregnancy, the subjects were divided into groups of underweight, normal weight, overweight and obese. The last three groups were compared using ANOVA. The obese group showed a significant difference in the pattern of changes in the skinfold thickness, waist:hip ratio and fat mass at the postpartum period, in comparison with the other two groups. In conclusion, there is a tendency in the obese group to develop central obesity at the postpartum period.

Adult↗
PubMed2000

The effect of pregnancy on bone density and bone turnover.

During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total-body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P < 0.01) and legs (1.9%, P < 0.01) but decreased in the pelvis (-3.2%, P < 0.05) and spine (-4.6%, P < 0.01) compared with prepregnancy values. All biochemical markers, with the exception of osteocalcin concentration, increased during pregnancy. The change in IGF-I at 36 weeks was related to the change in biochemical markers (e.g., PINP, r = 0.72, P = 0.002). Pregnancy is a high-bone-turnover state. IGF-I levels may be an important determinant of bone turnover during pregnancy. Elevated bone turnover may explain trabecular bone loss during pregnancy.

Adult↗
PubMed1999

Strategies for coping with labour: does antenatal education translate into practice?

There is little evidence to associate attendance at antenatal classes with a reduction in psychological distress or increased satisfaction with the experience of labour. There may be several reasons for this, including failure to implement coping strategies. A within-subjects research design explored the use in labour of coping strategies taught in antenatal classes and the role of practice. Women's views about using these strategies and their expectations of their midwives and birth companions were also identified. Following Ethics Committee approval and providing informed consent, 121 nulliparous women completed a questionnaire at their final antenatal class. This included questions on confidence and the amount of effort required to use coping strategies, the involvement hoped for from birth companions and midwives in using coping strategies in labour and satisfaction with the amount of practice of coping strategies. Within 72 hours of delivery, women were interviewed to obtain a narrative of the events of labour and their use of the coping strategies (sighing-out-slowly breathing, Laura Mitchell relaxation and postural change). A questionnaire obtained information on the involvement of the midwife and birth companion. Women used the three coping strategies to different extents. Midwives were not involved to the extent that women had hoped for antenatally. Birth companions achieved a level of involvement closer to women's hopes than that achieved by midwives. A significant proportion of women expressed dissatisfaction with the amount of practice of coping strategies during antenatal classes. The findings of this study of a group of well-prepared women raise questions about the correct components of antenatal classes and how midwives and birth companions can be involved optimally in this aspect of a woman's labour. Further research is required to determine how women can best be helped to cope with the experience of labour.

Adaptation, Psychological↗
PubMed1999

Amniotic fluid insulin levels identify the fetus at risk of neonatal hypoglycaemia.

AIMS: To investigate the use of amniotic fluid insulin (AFI) as a predictor of neonatal morbidity in the macrosomic newborn of the diabetic mother, in view of the fact that raised AFI levels are a marker for fetal hyperinsulinaemia. METHODS: AFI was measured by radioimmunoassay in a group of pregnant diabetic women (n = 63) with normal (n = 41) or accelerated fetal growth (n = 22). RESULTS: Using log transformed data, liquor insulin was found to be significantly higher in pregnant women with Type 1 and Type 2 diabetes mellitus (17.6 mU/l; 95% confidence interval (CI) 11.7-26.4) compared with women with gestational diabetes mellitus (GDM) (8.2 mU/l; 95% CI 4.8-13.8, P = 0.02) or impaired glucose tolerance (IGT) (6.2mU/l; 95% CI 4.9-8.0, P = 0.0001). In the group with macrosomic fetuses (birth weight > 90th centile for gestational age), there was a significantly higher incidence of elective Caesarean section (CS) and emergency CS (12/22) compared to those with appropriate for gestational age (AGA) fetal weights (birth weight > 10th and < 90th centiles for gestational age) (9/41, P = 0.009). There was no significant correlation between raised AFI and macrosomia except in the Type 1 diabetic women, in whom the AGA group mean was 13.2 mU/l (95% CI 7.4-23.3), and 34.6mU/l (95% CI 17.5-68.4 P = 0.022) in macrosomia. In the latter group, hypoglycaemia requiring treatment was significantly more common in the macrosomic hyperinsulinaemic neonates (8/13), compared to normoinsulinaemic neonates in the same group (0/9, P = 0.005). CONCLUSIONS: Identification of the hyperinsulinaemic fetus before delivery might allow the intensification of maternal insulin therapy leading to a reduction in incidence and severity of diabetic fetopathy. Pregnancy with a normoinsulinaemic fetus could be allowed to continue to the onset of spontaneous labour, which might result in a lower CS rate.

Amniocentesis↗
PubMed1999

Observational study of maternal anthropometry and fetal insulin.

AIMS: To examine the relation between maternal body fat and fetal metabolism. METHODS: In this observational study, cord blood samples were collected from 60 infants of healthy women for the measurement of insulin and C peptide concentrations. Maternal weight, height, body mass index (BMI) and body composition (skinfold thickness measurements and bioelectrical impedance) were assessed at 13-15 weeks of gestation. Twenty five of the volunteers agreed to have a 75 g oral glucose tolerance test at 28-31 weeks of gestation. RESULTS: Positive correlations were observed with both cord insulin or C peptide concentrations and maternal early pregnancy BMI (r=0.44, p=0.002 and r=0.33, p=0.008, respectively). There was no significant correlation between cord insulin or C peptide concentrations and birthweight or birth weight centiles. CONCLUSION: Maternal BMI could be a predictor of fetal cord insulin concentration.

Anthropometry↗
PubMed1998

Nodular fasciitis in the parotid region of a child.

BACKGROUND: Nodular fasciitis is a common pathologic entity in the limbs of adults but rare in the head and neck of children. It is defined by the World Health Organization as a benign and probably reactive fibroblastic growth extending as a solitary nodule from superficial fascia into subcutaneous tissue. Treatment is local excision, and recurrence is rare. METHOD: Case Report RESULTS: A 3.5-year-old boy was initially seen with a 1-year history of gradually enlarging but otherwise asymptomatic right facial mass. On examination, a firm nodule was palpable anterior to the right ear, and facial movement was symmetrical. Computed tomography showed a rounded, well-defined solid mass continuous with the parotid fascia. The patient underwent superficial parotidectomy without complication. The pathology was reported as nodular fasciitis, and the child has had no clinical recurrence over 2 years. CONCLUSION: Benign lesions in this region in children may present similarly to malignancies but require much more-conservative treatment.

Child, Preschool↗
PubMed1997

Fetal growth, length of gestation, and polycystic ovaries in adult life.

BACKGROUND: Polycystic ovaries are a common disorder associated with menstrual irregularities, subfertility, hirsutism, acne, and a range of endocrine abnormalities, including high concentrations of plasma luteinising hormone (LH) and excessive androgen production. The pathophysiology is not understood. We investigated whether the disorder originates during intrauterine life. METHODS: We examined 235 women aged 40-42 years who were born in Sheffield, UK. We related the prevalence of polycystic ovaries and the plasma concentrations of gonadotropin hormones and androgens to the women's body size at birth, and the length of gestation. FINDINGS: 49 (21%) of the women had polycystic ovaries. We defined two groups of women with the disorder, which correspond to the two groups that commonly present clinically. The first group comprised obese women who were androgenised, with higher than normal concentrations of plasma LH and testosterone. These women had above-average birthweight and were born to overweight mothers. The second group comprised women of normal weight who had high plasma LH, but normal testosterone concentrations. These women were born after term (40 weeks' gestation). INTERPRETATION: The two common forms of polycystic ovary syndrome have different origins in intrauterine life. Obese, hirsute women with polycystic ovaries have higher than normal ovarian secretion of androgens that are associated with high birthweight and maternal obesity. Thin women with polycystic ovaries have altered hypothalamic control of LH release resulting from prolonged gestation.

Adult↗
PubMed1997

Is the age of menopause determined in-utero?

OBJECTIVE: To determine whether age at menopause is related to size at birth. DESIGN: A follow-up study of two groups of women whose size at birth was recorded. SETTING: Hertfordshire and Sheffield, England. POPULATION: 755 women aged 60-71 years born in Hertfordshire; 235 women aged 40-42 years born in the Jessop Hospital, Sheffield. MAIN OUTCOME MEASURES: Age at natural menopause or serum follicle stimulating hormone concentration greater than 25 IU/ml. RESULTS: Age at menopause was unrelated to birth weight. However, it occurred at a younger age in women who had low weight at 1 year. This was independent of their body weight and smoking habits. In the population of younger women those who had had an early menopause tended to have been short at birth, with a high ponderal index (birth weight/length3). CONCLUSION: Growth retardation in late gestation, leading to shortness at birth and low weight gain in infancy, may be associated with a reduced number of primordial follicles in the ovary leading in turn to an earlier menopause.

Adult↗
PubMed1997

Immunophenotyping of insulitis in control and essential fatty acid deficient mice treated with multiple low-dose streptozotocin.

Multiple injections of low-dose streptozotocin induce lymphocytic insulitis and autoimmune diabetes in male CD-1 mice. Prior to the onset of insulitis, macrophages infiltrate the islets (single cell insulitis) and presumably help initiate the lymphocytic response directed at streptozotocin-induced neoantigens on islet beta cells. Essential fatty acid deficiency ameliorates the lymphocytic insulitis and prevents diabetes in this model. We hypothesize that essential fatty acid deficiency, which perturbs eicosanoid pathways and blocks the production of inflammatory mediators such as leukotriene B4, might prevent or diminish the single cell insulitis and, thus, abrogate the lymphocytic response. The purpose of the study was to determine whether essential fatty acid deficiency causes any differences in the immunophenotype or the time course of single cell insulitis or insulitis after low-dose streptozotocin. Three to five essential fatty acid deficient and 3-5 control mice were treated with low-dose streptozotocin and killed on days 0, 3, 5, 8, 10, 12 and 15. Frozen sections of the pancreata were stained using an immunoperoxidase method with antibodies against mouse macrophages, CD4T-lymphocytes and CD8 T-lymphocytes. Sections were assessed for the presence and severity of single cell insulitis and insulitis. Based on cell counts in the most severely involved islet from each pancreas, there was no difference in the single cell insulitis in control and essential fatty acid deficient mice. Islets from control pancreata had a higher mean grade of lymphocytic insulitis. These findings suggest that autoimmune diabetes following low-dose streptozotocin in control mice is the result of both lymphocytic and histiocytic infiltrates with subsequent beta-cell destruction. Our results do not support the hypothesis that the protective effect of essential fatty acid deficiency is due to diminished influx of macrophages into the islets. It is, however, possible that essential fatty acid deficiency deleteriously affects macrophage function and, thus, blunts the lymphocytic response.

Animals↗
PubMed1997

Immunophenotyping fish-to-mouse islet xenograft rejection: a time course study.

UNLABELLED: Tilapia islets, Brockmann bodies (BBs), transplanted under the kidney capsule (KC) of diabetic nude mice provide long-term normoglycemia, but, when transplanted into euthymic mice, reject in about one week. OBJECTIVES: The present study characterizes the cellular infiltrates at several time points during the xenograft rejection process. METHODS: Tilapia BBs were harvested, fragmented, cultured overnight, and then transplanted under the KC of streptozotocin-diabetic Balb/c mice. Glucose levels were measured daily until the mice were killed at 1 (n = 2), 2 (n = 2), 3 (n = 3), and 5 days (n = 3) post transplantation and at the time of BB graft rejection (n = 6). Serial frozen sections of graft-bearing kidneys were stained for murine macrophages (MOMA-2, F4/80, M170), CD4+ (L3T4) T-cells (YTS 191.1), and CD8+ (Ly-2) T-cells (YTS 169.4) by indirect immunoperoxidase; the presence of granulocytes and plasma cells was assessed with H&E stained sections. RESULTS: At 1 day, the grafts have undergone some central necrosis with macrophage infiltration. By 2 days, these changes are very well-developed and granulocytes, almost exclusively eosinophils, begin to surround the graft. At 3 days, rare CD4+ and CD8+ T-cells are seen at the graft kidney interface. Macrophages massively infiltrate the necrotic foci and pepper the graft. At 5 days and at rejection, macrophages and eosinophils predominated in the center of rejecting grafts while CD8+ T-cells and CD4+ T-cells were present at the periphery. Plasma cells were rare. CONCLUSION: We conclude that cell-mediated processes and eosinophils play roles in the rejection of cellular xenografts across this very wide phylogenetic barrier.

Animals↗
PubMed1996

Helicobacter pylori is not associated with nonspecific abdominal pain in children.

Nonspecific abdominal pain is a significant problem in the pediatric population, and there has been much recent interest in the role that Helicobacter pylori (HP) might play in this disorder. A retrospective review was conducted at our center to determine its prevalence among children with otherwise undiagnosed abdominal pain. The study was conducted over a 45-month period during which 47 patients underwent gastroscopy and antral biopsies in the workup of this problem. Of the 37 patients who did not have a history of acid-pepsin disease (APD), only one (2.7%) tested positive for HP. In contrast, of the 10 who had a history of APD, three (30%) tested positive (P < .03). There were no distinguishing features among the HP-positive patients except for the presence of associated antral gastritis. Based on the current endoscopic results, of the nine patients with current evidence of APD, four (44%) were positive for HP; of the other 38 patients, none was positive for HP. Therefore, HP appears to be associated with antral gastritis, and HP does not play a role in nonspecific abdominal pain in this population.

Abdominal Pain↗
PubMed1995

Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in naive and cyclosporin-treated low-responder murine strains.

We have previously shown that essential fatty acid (EFA) deficiency prevents diabetes and ameliorates insulitis in low-dose streptozotocin (LDS)-treated male CD-1 mice. The effects of EFA deficiency on the incidence of diabetes after LDS treatment has not been examined in other strains. In contrast to highly susceptible CD-1 mice, several other strains of mice are only partially susceptible to LDS treatment and do not develop appreciable insulitis; however, the susceptibility of these strains can be markedly increased by cyclosporin A (CsA) pretreatment to reduce suppressor cell function. Weanling male BALB/cByJ, DBA/2J, and C57BL/6J mice were placed on EFA-deficient (EFAD) or control diets for 2 months and then divided into experimental and control groups. Ten EFAD and 10 control mice from each strain received LDS treatment (40 mg/kg/d 5 d); an additional 10 EFAD BALB/cByJ and another 10 control BALB/cByJ mice received subcutaneous CsA injections (20 mg/kg/d) for 14 days prior to and for 5 days simultaneous with LDS treatment (40 mg/kg/d 5 d). Plasma glucose levels for all mice were determined 3 times per week for 3 weeks after LDS treatment. Mean plasma glucose levels (+/- SEM) at the end of the experiment were significantly lower in the EFAD groups vs control groups in BALB/cByJ (P < 0.001), DBA/2J (P < 0.00001), and C57BL/6J (P = 0.012) mice. CsA supplementation increased the severity of diabetes in LDS-treated BALB/cByJ mice (P < 0.0005); however, EFA deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗