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Biomedical subjects

M A Wilcox

Publications and source records attributed to M A Wilcox.

16 recordsLinked to original sources
PubMed1998

Alpha-2 macroglobulin is genetically associated with Alzheimer disease.

Alpha-2-macroglobulin (alpha-2M; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region (exon 18) revealed that inheritance of the deletion (A2M-2) confers increased risk for AD (Mantel-Haenzel odds ratio=3.56, P=0.001). The sibship disequilibrium test (SDT) also revealed a significant association between A2M and AD (P=0.00009). These values were comparable to those obtained for the APOE-epsilon4 allele in the same sample, but in contrast to APOE-epsilon4, A2M-2 did not affect age of onset. The observed association of A2M with AD did not appear to account for the previously published linkage of AD to chromosome 12, which we were unable to confirm in this sample. A2M, LRP1 (encoding the alpha-2M receptor) and the genes for two other LRP ligands, APOE and APP (encoding the amyloid beta-protein precursor), have now all been genetically linked to AD, suggesting that these proteins may participate in a common neuropathogenic pathway leading to AD.

Age of Onset↗
PubMed1997

The effect of different sampling intervals on the measurement of intrapartum fetal heart rate variability.

OBJECTIVE: To test the hypothesis that increasing the sampling interval affects the intrapartum fetal heart rate (FHR) variability measurement. METHODS: Fetal electrocardiograms were obtained from women in labor. Using the peak of the fetal R wave, the R-R interval and FHR were calculated on a beat-to-beat basis. Retrospectively, the original data were repartitioned using different intervals (2-900 seconds) to generate a window of measurement (epoch). The mean value for each epoch and the last FHR in that epoch (epochal value) were compared with published animal and human data. Errors were quantified by comparing the epochal and mean values for each epoch. Fetal heart rate variability between epochs and within each epoch was compared. RESULTS: Fetal heart rate and R-R interval were measured in 146 cases. The FHR had a normal distribution (mean 140.1 beats per minute, +/- standard deviation [SD] 15.6, skew -0.07), but its inverse, the R-R interval, was not normally distributed (mean 432 milliseconds, +/- SD 52.4, skew 1.78). Using a single value for an epoch duration of 2 seconds resulted in an error that was similar to the within-epoch variability (+/- SD of 2.2 beats per minute difference between mean and epochal value compared to +/- SD of 2 beats per minute within epoch) but which increased with epoch duration. CONCLUSION: An epoch duration of 2 seconds and a single sampled value within this period may be appropriate for measurement of both medium and long-term variability in any computerized intrapartum FHR interpretation system. Fetal heart rate (not R-R interval, because of its normal distribution) should be used to design such a computerized system.

Adult↗
PubMed1996

The effects of parity on birthweight using successive pregnancies.

OBJECTIVE: Accurate assessment of the difference in birthweight between first and second live-births to the same woman having excluded the effects of physiological factors known to affect birthweight. DESIGN: Retrospective longitudinal observational study. SETTING: Three large obstetric units in the East Midlands of the United Kingdom. SUBJECTS AND METHODS: Women in whom data were recorded for their first two pregnancies on the UK East Midlands Obstetric database which resulted in the delivery of a liveborn, singleton and congenitally normal baby. Six thousand five hundred and thirty such cases were identified, of which 3457 had complete datasets and delivered both babies at term (259 to 300 days). An analysis was performed of changes between the paired pregnancies of physiological factors known to affect birthweight. Regression analyses were used to enable prediction of the second birthweight with the knowledge of the first birthweight. RESULTS: The mean crude birthweight difference between first and second pregnancies was an increase of 138 g. Significant differences between the paired pregnancies were found in maternal booking visit weight, blood pressure, maternal age and gestation at delivery. Independent factors affecting difference in birthweight were gestation at delivery, maternal booking weight and baby's sex. Regression towards the mean was demonstrated which meant that a woman delivering a first baby weighing more than 3720 g could expect a lighter baby for her second delivery provided that all other factors remained constant. CONCLUSIONS: In general terms a woman is more likely to deliver a heavier baby in her second pregnancy than in her first pregnancy. However, maternal physiological factors differ in the two pregnancies and these differences have additional effects on birthweight. The effects of both these observations are tempered by regression towards the mean which has a profound influence in predicting the likely change in birthweight between first and second pregnancies. Clinical decisions should not be based on the assumption that a second baby will inevitably be heavier than the first baby.

Birth Order↗
PubMed1995

The effect of social deprivation on birthweight, excluding physiological and pathological effects.

OBJECTIVE: To study the effect of social deprivation on birthweight, excluding the effect of known physiological factors and exploring the effect of possible pathological factors. DESIGN: Retrospective analysis of computerised obstetric database. SETTING: Two teaching hospitals and an associated district general hospital which provided a defined catchment area in the East Midlands. SUBJECTS: The final analysis included 7493 women with complete datasets and gestations of between 259 and 300 days at delivery, dated by ultrasound scan. MAIN OUTCOME MEASURES: Smoking habit, alcohol consumption, weight gain during pregnancy, systolic and diastolic blood pressures at booking, bleeding during pregnancy and Jarman score; also, the effect of these variables on birthweight, adjusted for the effects of physiological factors using the individualised birthweight ratio. RESULTS: Smoking during pregnancy reduced birthweight but the effect is not linear, becoming less marked as the number of cigarettes smoked increases. Alcohol intake, diastolic and systolic blood pressures at the booking visit and vaginal bleeding during early pregnancy were not significantly related to birthweight. Pregnancy weight gain was significantly positively related to birthweight especially in the normal weight range (60-99 kg). A multivariate analysis including physiological and pathological factors found increasing Jarman score to be negatively related to birthweight. CONCLUSIONS: In this central British population social deprivation is correlated negatively with birthweight: the most socially deprived mothers have the smallest babies. This association cannot be explained in terms of physiological differences in the population nor in a higher prevalence of known pathological factors.

Alcohol Drinking↗
PubMed1995

Paternal influences on birthweight.

OBJECTIVE: To assess the influence of paternal size on birthweight after suitable control for maternal and fetal factors. DESIGN: Prospective observational study. SETTING: Delivery suite, City Hospital, Nottingham. SUBJECTS: 571 husbands/partners of unselected women delivering August 1992 to February 1993. MAIN OUTCOME METHODS: Individualised birthweight ratio and thereby an adjusted birthweight for a typical mother. The results of a multiple regression analysis with the individualised birthweight ratio as the dependent variable. RESULTS: When considered in isolation both paternal height and weight are significantly positively associated with crude and adjusted birthweight (p < 0.01, analysis of variance). Due to correlations of paternal size with maternal size and smoking habit, only paternal height is significant in the multiple regression analysis (p = 0.01). CONCLUSION: If the partner of an average woman is short (mean-2s.d.) then the baby will be 183 g lighter than if he is tall (mean + 2s.d.). This effect of paternal height on birthweight must be genetic and therefore should be taken into account when defining intra-uterine growth retardation and macrosomia.

Birth Weight↗
PubMed1994

The individualised birthweight ratio: a new method of identifying intrauterine growth retardation.

OBJECTIVE: To assess the effectiveness of the newly developed individualised birthweight ratio in identifying growth retarded infants. DESIGN: Prospective observational study. SETTING: Obstetric unit, City Hospital Nottingham. SUBJECTS: Two thousand eight hundred and thirty-five women delivered between December 1991 and July 1992 and the infants of 616 of these selected by virtue of their birthweight for gestation and individualised birthweight ratio centile positions. MAIN OUTCOME MEASURES: Skinfold thickness and ponderal index measurements, occurrence of abnormal fetal heart rate patterns, operative delivery due to fetal distress and the need for neonatal resuscitation. RESULTS: Using an individualised birthweight ratio less than the 10th centile as a cut-off results in 25% of those less than the 10th centile of birthweight for gestation being reclassified as normally grown. A slightly larger group are reclassified as small; significantly more of these infants have abnormal ponderal indices and skinfold thicknesses, suffer abnormal fetal heart rate patterns, operative delivery for fetal distress and need neonatal resuscitation than do those who are reclassified as normally grown. CONCLUSION: The individualised birthweight ratio combines the simplicity of birthweight measurement with the accuracy of clinical measurements in the identification of the growth retarded baby.

Birth Weight↗
PubMed1994

Relative macrosomia identified by the individualised birthweight ratio (IBR). A better method of identifying the at risk fetus.

OBJECTIVE: To assess the effectiveness of a newly developed individualised birthweight ratio (IBR), which corrects for physiological birthweight determinants, in identifying infants at risk from the complications of macrosomia. DESIGN: Prospective observational study. SETTING: Obstetric unit, Nottingham City Hospital. SUBJECTS: 2835 women delivered between December 1991 and July 1992 and the infants of 624 of these, selected by virtue of their birthweight for gestation and IBR centile positions. MAIN OUTCOME MEASURES: Skinfold thickness and ponderal index measurements, operative delivery, shoulder dystocia, fetal trauma, impaired glucose tolerance. RESULTS: Using an IBR above the 90th centile as a cut off results in 2.4% of infants being reclassified as normally grown and 3.1% are reclassified as large. The IBR does not result in the identification of any more infants with abnormal ponderal indices or skinfold thicknesses than birthweight for gestation. It does, however, identify more of the infants at risk of operative delivery, shoulder dystocia, fetal trauma and impaired glucose tolerance. CONCLUSION: The IBR significantly improves upon birthweight for gestation in identifying infants who suffer from the complications of relative macrosomia.

Adult↗
PubMed1993

The individualised birthweight ratio: a more logical outcome measure of pregnancy than birthweight alone.

OBJECTIVE: To provide a new outcome measure for pregnancy specifically related to the individual. DESIGN: Computer analysis of physiological factors affecting birthweight. SETTING: Two provincial teaching hospitals (University and City Hospitals, Nottingham) and an associated district general hospital (Derby City Hospital) serving a defined catchment area in the East Midlands. SUBJECTS: All women delivering in the above hospitals since the start of computerised obstetric records: 31,561 women with gestational age verified by early pregnancy ultrasound scan data. MAIN OUTCOME MEASURES: Calculation of the predicted birthweight taking into account maternal and fetal physiological factors. Derivation of the individualised birthweight ratio (actual birthweight divided by predicted birthweight expressed as a percentage) for each individual baby. RESULTS: The individualised birthweight ratio redefines as normally grown 41% of babies below the 10th centile of crude birthweight for gestation. Other babies previously regarded as normal are redefined as growth retarded. At the upper end of the distribution 46% of those above the 90th centile of birthweight for gestation are redefined as normally grown. CONCLUSIONS: The predicted birthweight can be calculated for an individual pregnancy at a given gestation. The standardised comparison between this predicted birthweight and the actual birthweight is a more logical reflection of the normality of intrauterine growth and therefore more logical as an outcome measure for pregnancy than crude birthweight for gestation.

Adolescent↗
PubMed1984

Stimulation of hepatic microsomal beta-glucuronidase by calcium.

Hydrolysis of 3-methylumbelliferyl glucuronide by liver microsomal beta-glucuronidase is enhanced about 2-fold by micromolar concentrations of Ca2+; half-maximal stimulation occurs with 0.35 microM Ca2+. Dissociation of the enzyme from microsomal membranes by various treatments increases basal beta-glucuronidase activity and markedly decreases the sensitivity of the enzyme to Ca2+. Under similar conditions, the soluble lysosomal form of the enzyme is insensitive to Ca2+. Ca2+ stimulation was unaltered by addition of calmodulin inhibitors or exogenous calmodulin. Thus, interaction of cytosolic Ca2+ with membrane bound beta-glucuronidase may modulate glucuronidation in intact hepatocytes via a novel, calmodulin-independent mechanism.

Animals↗
PubMed1984

A teaching model for nasal irrigation.

A teaching model for nasal irrigation is designed to instruct and reassure patients that water pulsed into the nostrils will return out of the nostrils without harm to the individual. Either an electric dental cleanser with a special adapter for the nose or a bulb syringe is used to irrigate. Materials used to produce this model are dental self-curing resins and silicones.

Humans↗