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Biomedical subjects

L C Gurrin

Publications and source records attributed to L C Gurrin.

At least 19 recordsLinked to original sources

The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron, ondansetron and dolasetron.

There are currently three 5-hydroxytryptamine3 (5-HT3) receptor antagonists available in Australia. In this randomized, double-blind, parallel group study the prophylactic antiemetic effect of a single dose of tropisetron 2 mg, ondansetron 4 mg or dolasetron 12.5 mg was compared after major gynaecological surgery. One hundred and eighteen patients (group T n = 42; group O n = 36; group D n = 40) were evaluated for nausea, vomiting, recovery characteristics and satisfaction for 24 hours postoperatively. A cost-effectiveness analysis was performed. Rescue antiemetic, prochlorperazine 12.5 mg i.m., was given if vomiting occurred more than 10 minutes after arrival in the recovery room. If prochlorperazine was ineffective one hour after administration, droperidol 1 mg i.v. was given. There were no significant differences between groups for the incidence of vomiting during consecutive epochs until 24 hours postoperatively or overall (57%, 75% and 72.5% for groups T, O and D respectively, P = 0.18). The incidence and number of rescue antiementic treatments for nausea or vomiting were similar. The incidence of nausea and the overall and interval nausea scores were similar except for lower "worst nausea" score in group T between 12 and 18 hours (P = 0.02). Recovery times, satisfaction and cost per patient did not differ between groups. We conclude that the risk of postoperative nausea and vomiting remained high in this setting despite 5-HT3 receptor antagonist prophylaxis and that the choice between these agents should be based on the lowest available acquisition cost.

Antiemetics↗

The effects of overcoming experimental bladder outflow obstruction in fetal sheep.

OBJECTIVE: To develop an ovine model of fetal bladder outflow obstruction and to investigate the effect on the kidney of surgical relief of the obstruction in the prenatal period. METHODS: Ultrasound examination and amniocentesis were performed on 68 date-bred pregnant ewes at day 57 of pregnancy (term = 150 days). Fetal gender was determined using a molecular technique to identify single male fetuses. The urethra and urachus were ligated at hysterotomy on 20 of these fetuses at 75 days' gestation. Comparisons were made with six controls that did not undergo operation. Changes that occurred in fetal urinary tract appearance were detected using serial ultrasound examinations. Seven obstructed cases chosen at random had further prenatal surgery on day 94 to decompress the obstructed urinary tract by vesicostomy. The animals were killed at 110 days' gestation and post-mortem studies were performed. RESULTS: Fourteen days after surgical obstruction, there were increases in the summed renal lengths (33 mm vs. 28 mm, p = 0.003) and renal pelvis anteroposterior (A-P) diameters (8 mm vs. 5.5 mm, p = 0.02). In the group allocated to receive surgical decompression, 9 days' relief of obstruction resulted in significant reductions in summed renal lengths (30 mm vs. 41 mm, p = 0.024; controls 31 mm) and renal pelvis A-P diameters (5.8 mm vs. 8.9 mm, p = 0.012; controls < 2 mm). Postmortem histological examination in the surgical decompression group revealed an estimated number of glomeruli similar to controls and greater than in the obstructed cases. CONCLUSION: Surgical relief of fetal bladder outflow obstruction in ovine mid-pregnancy results in improved renal appearance on ultrasonic and histopathological examinations.

Amniotic Fluid↗

Prenatal ultrasound biometry related to subsequent blood pressure in childhood.

STUDY OBJECTIVE: To relate measures of fetal growth/size other than birth weight with subsequent blood pressure measured on the same individuals within the context of the "fetal origins of adult disease". DESIGN: A prospective cohort study in which measurements of fetal dimensions obtained by serial ultrasound imaging between 18 and 38 weeks gestation were analysed with reference to systolic blood pressure measurements on the offspring at age 6 years. SETTING: Perth, Western Australia. PARTICIPANTS: A subgroup of 707 eligible mother-fetus pairs from a cohort of 2876 pregnant women and their offspring. The number of mother-fetus pairs varied at each gestational age and by measurement of fetal dimension. Subsequent blood pressure recordings were obtained on approximately 300 of the offspring at age 6 years. MAIN RESULTS: The findings confirmed the inverse association between birth weight and systolic blood pressure at age 6. There was, also, an inverse relation between fetal femur length and systolic blood pressure at age 6, adjusted for current height. Furthermore, an inverse association was demonstrated between a statistically derived measure of fetal growth (conditional z score) between 18 and 38 weeks gestation and later systolic blood pressure at age 6. The effect sizes for all three relations were in the order of 1-2 mm Hg per standard deviation change. CONCLUSION: The mechanisms underpinning the "fetal origins" hypothesis may be operative early in pregnancy and may be reflected in the length of the fetal femur in early to mid-pregnancy.

Anthropometry↗

The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function.

Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses of glucocorticoids on postnatal hypothalamic-pituitary-adrenal (HPA) function. To determine the effects of maternal or fetal betamethasone administration (0.5 mg/kg maternal or estimated fetal weight) on postnatal HPA function at 6 months and 1 year postnatal age, pregnant ewes were randomized into the following treatment groups: no treatment (n=6); maternal saline (n=6); single maternal betamethasone (M1) (n=6); repeated maternal betamethasone (M4) (n=6); fetal saline (n=5); single fetal betamethasone (n=6) and repeated fetal betamethasone (F4) (n=6). Single injections were given at 104 days of gestation and repeated injections at 104, 111, 118 and 125 days. Lambs were born spontaneously and the ACTH and cortisol responses to i.v. corticotropin-releasing hormone (CRH) (0.5 microg/kg) plus arginine vasopressin (AVP) (0.1 microg/kg) were measured at 6 months and 1 year postnatally. At 6 months postnatal age, neither maternal nor fetal prenatal betamethasone administration altered significantly the ACTH and cortisol responses to CRH+AVP. However, in animals at 1 year postnatal age, a previous single injection of betamethasone to the mother (M1) resulted in significantly elevated basal and stimulated cortisol levels (P<0.05), without significant change in the ACTH response. In contrast, betamethasone administration to the fetus resulted in significantly attenuated ACTH responses to CRH+AVP at 1 year compared with control animals (P<0.05), but these were not associated with any significant changes in basal or stimulated cortisol levels. All control animals exhibited a significant increase in peak ACTH responses to CRH+AVP between 6 months and 1 year postnatal age (P<0.05). After prenatal betamethasone (F4, M4) the difference in peak ACTH response between animals at 6 months and 1 year postnatal age was abolished. We conclude that in sheep between 6 months and 1 year postnatal age, HPA function undergoes developmental changes that are influenced by prenatal glucocorticoid exposure. Furthermore, the effects of glucocorticoid on postnatal HPA responses may vary according to the time in gestation that the steroid was administered, and whether it was given directly into the fetal or maternal compartment.

Adrenocorticotropic Hormone↗

Statistical measures of foetal growth using linear mixed models applied to the foetal origins hypothesis.

Statistical models of the relationship between the distribution of each of five foetal dimensions and gestational age are developed based on serial ultrasound biometric data from a prospective longitudinal study in Perth, Western Australia. Both the response variable and the gestational age timescale are transformed to establish an approximately linear relationship within subjects. This relationship is modelled using a linear mixed effects model that accounts for between-subject heterogeneity by incorporating subject specific random effects for both intercept and gradient. These models are used to motivate three measures of foetal growth: the conditional centile or z-score of a current measurement given an earlier value for the same measurement; the best linear unbiased predictor (BLUP) of the subject specific random effect gradient (which is shown to be invariant to transformations of location and scale), and the standardized residual at a given gestational age, which characterizes departures from the modelled growth trajectory. We illustrate how these three measures of growth might be applied to subsequent health outcomes in later life by relating growth in foetal abdominal circumference to blood pressure in children from the same cohort at six years of age. Foetuses whose summary measures indicate poor growth in abdominal circumference have higher blood pressure in early childhood, supporting the 'foetal origins' hypothesis that many chronic diseases of adulthood have their origins before birth.

Anthropometry↗

Placental weight and placental ratio as predictors of later blood pressure in childhood.

OBJECTIVE: A significant inverse relationship between blood pressure and birth weight is firmly established. This association may be the result of fetal adaptations to an adverse intrauterine environment. Further markers of intrauterine growth include the weight of the placenta and the placental ratio (the ratio of placental weight to birth weight). A number of studies suggest that a decreased placental weight or an elevated placental ratio may be independent risk factors for subsequent high blood pressure. The overall evidence for this is, however, inconclusive. The purpose of the present study was to clearly define the relationships between placental weight, placental ratio and subsequent blood pressure during childhood. DESIGN: Prospective cohort study of 2507 singleton children, born at term during 1989-1992. Blood pressures were recorded at ages 1, 3 and 6 years, using a semi-automated oscillometric device. RESULTS: Inverse relationships existed between both systolic and diastolic blood pressure and placental weight, adjusted for current weight at ages 1, 3 and 6 years. The relationships between placental weight and systolic blood pressure were statistically significant at ages 1 and 3 years. There was no consistent relationship between placental weight and later blood pressure within birth weight categories. No clinically or statistically significant association was seen between the placental ratio and either systolic or diastolic blood pressures at any age. CONCLUSIONS: Birth weight, rather than placental weight or their ratio, is the early life factor most importantly related to subsequent blood pressure in childhood.

Birth Weight↗

Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure.

Our aim was to determine the postnatal effects of single and repeated glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125 days) or single (104 days) injections of betamethasone or saline were given to the ewe or by ultrasound guided injection to the fetus (term 150 days). Lambs were born spontaneously and studied at 3 and 6 mo and 1 yr of age. Arterial pressure was measured at each age, and we performed intravenous glucose tolerance tests at 6 mo and 1 yr. Repeated maternal, but not single maternal or fetal, betamethasone injections prolonged gestation, reduced weight at birth and 3 mo, and was associated with low arterial pressure at 3 mo but not at 6 mo and 1 yr. Glucose metabolism was altered in all betamethasone treatment groups, regardless of the number or route of injections. Our data demonstrate that glucocorticoid-induced fetal growth restriction is associated with a transient reduction in postnatal arterial pressure, but glucocorticoid exposure with or without growth restriction alters glucose metabolism.

Aging↗

The effect of the biopatch, a chlorhexidine impregnated dressing, on bacterial colonization of epidural catheter exit sites.

We performed a prospective, randomized study in 55 ASA I to 3 women undergoing elective gynaecological surgery followed by postoperative epidural analgesia. We compared the incidence of bacterial colonization at the epidural exit site following catheter removal between a control group and an experimental group who received a chlorhexidine impregnated dressing (Biopatch, Johnson and Johnson, Arlington, TX, U.S.A.). Positive culture results were found in 11 of 27 (40.1%) patients in the control group compared with one of 29 (3.4%) patients whose epidural catheters were dressed with the Biopatch. We concluded that the Biopatch was effective in reducing bacterial colonization of the epidural catheter exit site.

Adult↗

What do children with cystic fibrosis and their parents know about nutrition and pancreatic enzymes?

OBJECTIVE: To describe the development and validation of questionnaires designed to assess nutrition and pancreatic enzyme replacement therapy knowledge and cystic fibrosis self-management skills, and the results obtained when the questionnaires were used. DESIGN: A cross-sectional study using validated questionnaires to interview the respondents. The outcome measures were scores for knowledge, appropriate and inappropriate self-management, and Socioeconomic Index. SUBJECTS: Forty-two children with cystic fibrosis aged 6 to 11 years and 55 caregivers of 2 to 11-year-old patients of the Princess Margaret Hospital Cystic Fibrosis Clinic, Perth, Australia. STATISTICAL ANALYSES: Descriptive statistics and correlations between scores were used for statistical analyses. Associations between knowledge scores were examined using Pearson's correlation coefficient. Spearman's rank correlation was used to examine the associations between knowledge and self-management scores and socioeconomic index. RESULTS: Children's and caregivers' mean knowledge scores were 63% and 85%, respectively. Mean appropriate and inappropriate self-management scores for children were 55% and 21%, respectively, and for the caregivers were 74% and 32%, respectively. There was a statistically significant (P < .05) positive association between caregivers' and children's knowledge (r = 0.32), and children's knowledge and appropriate self-management scores (r = 0.41); and a statistically significant negative association between caregivers' knowledge and inappropriate self-management scores (r = -0.35); and no statistically significant associations between Socioeconomic Index and children's and caregivers' knowledge and self-management scores. APPLICATIONS: This study identified areas in which the nutrition knowledge of children with cystic fibrosis and their caregivers needs to be enhanced to increase the likelihood that optimum dietary and pancreatic enzyme therapy is achieved. The questionnaires that were developed for the study could be refined and used in the clinical setting to identify knowledge and self-management deficits. Alternatively, the questionnaires could become valuable research tools for assessing the type of intervention required and in planning and evaluating programs.

Adult↗

Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood.

Given the widely acknowledged inverse relationship between birth weight and blood pressure, a raised blood pressure in the offspring of smoking mothers as compared to those whose mothers did not smoke, would be anticipated by virtue of the reduction in birth weight associated with smoking during pregnancy. The objective of the present study was to test the hypothesis that maternal cigarette smoking during pregnancy has an effect on blood pressure in childhood independent of its effect on birth weight. Data was obtained from a prospective cohort study of 1708 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia, commenced at 16 weeks gestation with serial blood pressure measurements through early childhood. Statistically significant associations were found between maternal smoking during pregnancy and systolic blood pressure at age six, between birth weight and systolic blood pressure at ages three and six, and between maternal smoking during pregnancy and birth weight. The relationship between birth weight and blood pressure in early childhood differed significantly on the basis of maternal cigarette smoking or not during pregnancy. This differential relationship persisted after adjustment for the child's current weight and socio-economic status. We concluded that intra-uterine exposure to maternal cigarette smoking increased children's blood pressure at age one through to age six. This was not wholly attributable to an effect on birth weight or confounding of the association between birth weight and subsequent blood pressure by the child's current weight or socio-economic factors. Furthermore, maternal smoking during pregnancy does not account for the acknowledged elevation in blood pressure associated with low birth weight. The present study is an exploration of a possible causal pathway underlying the birth weight/blood pressure association rather than simply a confirmation of such an association which has been detailed in many other papers.

Adult↗

Bayesian statistics in medical research: an intuitive alternative to conventional data analysis.

Statistical analysis of both experimental and observational data is central to medical research. Unfortunately, the process of conventional statistical analysis is poorly understood by many medical scientists. This is due, in part, to the counter-intuitive nature of the basic tools of traditional (frequency-based) statistical inference. For example, the proper definition of a conventional 95% confidence interval is quite confusing. It is based upon the imaginary results of a series of hypothetical repetitions of the data generation process and subsequent analysis. Not surprisingly, this formal definition is often ignored and a 95% confidence interval is widely taken to represent a range of values that is associated with a 95% probability of containing the true value of the parameter being estimated. Working within the traditional framework of frequency-based statistics, this interpretation is fundamentally incorrect. It is perfectly valid, however, if one works within the framework of Bayesian statistics and assumes a 'prior distribution' that is uniform on the scale of the main outcome variable. This reflects a limited equivalence between conventional and Bayesian statistics that can be used to facilitate a simple Bayesian interpretation based on the results of a standard analysis. Such inferences provide direct and understandable answers to many important types of question in medical research. For example, they can be used to assist decision making based upon studies with unavoidably low statistical power, where non-significant results are all too often, and wrongly, interpreted as implying 'no effect'. They can also be used to overcome the confusion that can result when statistically significant effects are too small to be clinically relevant. This paper describes the theoretical basis of the Bayesian-based approach and illustrates its application with a practical example that investigates the prevalence of major cardiac defects in a cohort of children born using the assisted reproduction technique known as ICSI (intracytoplasmic sperm injection).

Bayes Theorem↗

Reference ranges for blood pressure in preschool Australians, obtained by oscillometry.

OBJECTIVE: To derive reference centiles for blood pressure in children aged 1-6 years which seek to address shortcomings in available reference ranges. METHODS: Prospective cohort study of 2876 children in Perth, Western Australia, commenced in 1989 with serial blood pressure measurements through early childhood obtained by oscillometry under standardized conditions. RESULTS: Gender-specific reference centile charts for systolic and diastolic blood pressure, (i) across ages 1-6 years and (ii) across the range of corrected Body Mass Index values at ages 1, 3 and 6 years, were generated by fitting linear models with both fixed and random effects. CONCLUSIONS: Reference values for blood pressure for young children are of clinical use and may be of long-term predictive value.

Blood Pressure↗

Adjustment for current weight and the relationship between birth weight and blood pressure in childhood.

OBJECTIVE: To determine the role of current weight in mediating the relationship between birth weight and blood pressure within the context of the 'fetal origins' hypothesis. DESIGN: Prospective cohort study of 2507 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia between 1989 and 1992. The study commenced at 16 weeks gestation with serial weight and blood pressure measurements recorded through early childhood. RESULTS: Inverse associations were found between birth weight and systolic blood pressure at ages 1, 3 and 6. The effect of birth weight on systolic blood pressure at age 6 reached statistical significance and was increased fourfold in magnitude to -2.3 mmHg [95% confidence interval = (-3.3 to -1.3), P < 0.01] after adjustment for current weight. The interaction term for birth weight and current weight was not statistically significant. Including intermediate weights did not produce a statistically significantly better model but did increase the magnitude of the estimated regression coefficient of birth weight on blood pressure, and only the birth weight and current weight terms were significant CONCLUSIONS: Adjustment for current weight serves to highlight the relationship between birth weight and blood pressure in childhood. Nevertheless, birth weight, rather than birth weight adjusted for current weight, is still the relevant predictor of later blood pressure within the context of the 'fetal origins' hypothesis.

Adult↗

Genetic variance components analysis for binary phenotypes using generalized linear mixed models (GLMMs) and Gibbs sampling.

The common complex diseases such as asthma are an important focus of genetic research, and studies based on large numbers of simple pedigrees ascertained from population-based sampling frames are becoming commonplace. Many of the genetic and environmental factors causing these diseases are unknown and there is often a strong residual covariance between relatives even after all known determinants are taken into account. This must be modelled correctly whether scientific interest is focused on fixed effects, as in an association analysis, or on the covariances themselves. Analysis is straightforward for multivariate Normal phenotypes, but difficulties arise with other types of trait. Generalized linear mixed models (GLMMs) offer a potentially unifying approach to analysis for many classes of phenotype including multivariate Normal traits, binary traits, and censored survival times. Markov Chain Monte Carlo methods, including Gibbs sampling, provide a convenient framework within which such models may be fitted. In this paper, Bayesian inference Using Gibbs Sampling (a generic Gibbs sampler; BUGS) is used to fit GLMMs for multivariate Normal and binary phenotypes in nuclear families. BUGS is easy to use and readily available. We motivate a suitable model structure for Normal phenotypes and show how the model extends to binary traits. We discuss parameter interpretation and statistical inference and show how to circumvent a number of important theoretical and practical problems that we encountered. Using simulated data we show that model parameters seem consistent and appear unbiased in smaller data sets. We illustrate our methods using data from an ongoing cohort study.

Binomial Distribution↗

Adolescent pregnancy: psychopathology missed.

OBJECTIVES: Few data exist that explore the level of psychosocial problems and drug abuse in an Australian, adolescent, antenatal population. We set out to audit these data from a population of pregnant Western Australian adolescents. We also set out to examine whether social issues and the use of non-prescription drugs are routinely addressed in general public antenatal clinics. METHODS: One hundred and sixty patients were involved in the prospective cohort study. In the assessed group, 100 consecutive patients from the King Edward Memorial Hospital Adolescent Antenatal Clinic were interviewed during the antenatal period to determine if any major psychosocial issues or a history of non-prescription drug abuse was present. The control group consisted of 60 adolescent patients who delivered in general antenatal clinics at three Perth metropolitan hospitals. RESULTS: Sixty percent of the assessed group were identified as having a major psychosocial problem that interfered with their ability to carry out acts of daily living. Consumption of cigarettes, alcohol, marijuana, heroin and solvents were higher than that reported for the general Australian adolescent population. Of note, in the control group, many patients did not have a social, psychological, or drug use history taken by their caregivers. CONCLUSION: Failure to identify psychosocial problems and drug abuse during the antenatal period will result in missed opportunities for positive intervention. These problems are common in this population and interventions are required to offer these women alternative foundations upon which to base their mothercraft skills.

Adolescent↗

Pregnancy loss rates following second trimester genetic amniocentesis.

Data from 3,953 consecutive second trimester genetic amniocenteses were analysed to determine pregnancy loss rates up to 6 weeks after the procedure. Information was prospectively collected on a cohort of 3,685 women in 3,896 singleton and 50 twin pregnancies, from 2 operating sites in Perth, Western Australia, using 9 operators over the 6-year period, 1989 to 1995. Complete information regarding pregnancy outcome was obtained for 3,643 of the 3,685 women (98.9%). There were 27 identified singletons and 1 set of twins lost within 6 weeks following amniocentesis. The overall pregnancy loss rate in this cohort was 29 of 3,911 (0.74%). The pregnancy loss rate associated with genetic amniocentesis is not excessive in comparison to the calculated background pregnancy loss rate of 1%, and it is suggested that each prenatal diagnostic team should determine their own complication rates for the purpose of counselling prior to amniocentesis.

Abortion, Spontaneous↗

A survey of parturients using epidural analgesia during labour. Considerations relevant to antenatal educators.

The use of epidural analgesia (EA) during labour is increasing in Australasia. This highlights the need for improved educational and resource materials, current factual information about EA, and identification of consumer attitudes towards EA. In this survey, 350 parturients who had recently used EA for labour pain relief in a single maternity unit were asked to complete a questionnaire about their expectations and experience. The response rate was 90%. Prepartum information was most commonly derived from hearsay and least commonly from medical health professionals, 56% of respondents wanted pain to be made tolerable and 34% wanted complete pain relief. Almost half considered unrestricted mobility and delivery without obstetric assistance important. A minority were concerned about possible effects of EA on the baby or labour outcome. Anticipated pain during epidural placement was significantly greater than that experienced. Satisfaction with EA was high, although 36% described unpleasant or annoying effects associated with EA. Parent educators and epidural service providers should be aided by knowledge of where parturients obtain information and of consumer views about EA.

Adult↗

High prevalence of chlamydia and Pap-smear abnormalities in pregnant adolescents warrants routine screening.

A prospective cohort of pregnant adolescent patients who planned to deliver at 1 of 3 Perth metropolitan hospitals was studied; 1 subgroup of this cohort was offered universal screening for cervical chlamydial infection and Pap-smear abnormalities (screened), and the remainder of the cohort were offered screening at the discretion of the attending medical staff (control). High prevalences of both chlamydial infection (27%) and Pap-smear abnormalities (38%) were detected in the screened cohort. The majority of Pap-smear abnormalities were inflammatory atypia, but high-grade Bethesda lesions were also diagnosed. In the control group, the prevalence of positive swabs and abnormal Pap-smear reports in those tested was also high (22% and 35% respectively), but significantly fewer patients were tested (18% and 33% respectively in the control group, compared to 92% and 94% in the screened group; both p<0.001). Screening and treatment of chlamydia was associated with a significant decrease in the incidence of newborn febrile morbidity (10% versus 25%; p=0.02). In view of the high prevalence of positive results, it is cost-effective to offer universal screening in this setting. Failure to introduce a specific screening policy can result in a significant number of patients being denied the advantages of diagnosis and treatment.

Adolescent↗