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Biomedical subjects

R J McClure

Publications and source records attributed to R J McClure.

At least 19 recordsLinked to original sources

Injury risk from popular childhood physical activities: results from an Australian primary school cohort.

BACKGROUND: Children engage in various physical activities that pose different injury risks. However, the lack of adequate data on exposure has meant that these risks have not been quantified or compared in young children aged 5-12 years. OBJECTIVES: To measure exposure to popular activities among Australian primary school children and to quantify the associated injury risks. METHOD: The Childhood Injury Prevention Study prospectively followed up a cohort of randomly selected Australian primary and preschool children aged 5-12 years. Time (min) engaged in various physical activities was measured using a parent-completed 7-day diary. All injuries over 12 months were reported to the study. All data on exposure and injuries were coded using the International classification of external causes of injury. Injury rates per 1000 h of exposure were calculated for the most popular activities. RESULTS: Complete diaries and data on injuries were available for 744 children. Over 12 months, 314 injuries relating to physical activity outside of school were reported. The highest injury risks per exposure time occurred for tackle-style football (2.18/1000 h), wheeled activities (1.72/1000 h) and tennis (1.19/1000 h). Overall, boys were injured more often than girls; however, the differences were non-significant or reversed for some activities including soccer, trampolining and team ball sports. CONCLUSION: Although the overall injury rate was low in this prospective cohort, the safety of some popular childhood activities can be improved so that the benefits may be enjoyed with fewer negative consequences.

Athletic Injuries↗

The properties of the International Classification of the External Cause of Injury when used as an instrument for injury prevention research.

OBJECTIVE: To demonstrate properties of the International Classification of the External Cause of Injury (ICECI) as a tool for use in injury prevention research. METHODS: The Childhood Injury Prevention Study (CHIPS) is a prospective longitudinal follow up study of a cohort of 871 children 5-12 years of age, with a nested case crossover component. The ICECI is the latest tool in the International Classification of Diseases (ICD) family and has been designed to improve the precision of coding injury events. The details of all injury events recorded in the study, as well as all measured injury related exposures, were coded using the ICECI. This paper reports a substudy on the utility and practicability of using the ICECI in the CHIPS to record exposures. Interrater reliability was quantified for a sample of injured participants using the Kappa statistic to measure concordance between codes independently coded by two research staff. RESULTS: There were 767 diaries collected at baseline and event details from 563 injuries and exposure details from injury crossover periods. There were no event, location, or activity details which could not be coded using the ICECI. Kappa statistics for concordance between raters within each of the dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for activity and location in the control periods. DISCUSSION: This study represents the first detailed account of the properties of the ICECI revealed by its use in a primary analytic epidemiological study of injury prevention. The results of this study provide considerable support for the ICECI and its further use.

Child↗

Long term health outcomes after injury in working age adults: a systematic review.

BACKGROUND: Estimating the contribution of non-fatal injury outcomes remains a considerable challenge and is one of the most difficult components of burden of disease analysis. The aim of this systematic review was to quantify the effect of being injured compared with not being injured on morbidity and health service use (HSU) in working age adults. METHODS: Studies were selected that were population based, had long term health outcomes measured, included a non-injured comparison group, and related to working age adults. Meta-analysis was not attempted because of the heterogeneity between studies. RESULTS: Nine studies met the inclusion criteria. In general, studies found an overall positive association between injury and increased HSU, exceeding that of the general population, which in some studies persisted for up to 50 years after injury. Disease outcome studies after injury were less consistent, with null findings reported. CONCLUSION: Because of the limited injury types studied and heterogeneity between study outcome measures and follow up, there is insufficient published evidence on which to calculate population estimates of long term morbidity, where injury is a component cause. However, the review does suggest injured people have an increased risk of long term HSU that is not accounted for in current methods of quantifying injury burden.

Adolescent↗

Ten-year health service use outcomes in a population-based cohort of 21,000 injured adults: the Manitoba injury outcome study.

OBJECTIVE: To quantify long-term health service use (HSU) following non-fatal injury in adults. METHODS: A retrospective, population-based, matched cohort study identified an inception cohort (1988-91) of injured people who had been hospitalized (ICD-9-CM 800-995) aged 18-64 years (n = 21 032) and a matched non-injured comparison group (n = 21 032) from linked administrative data from Manitoba, Canada. HSU data (on hospitalizations, cumulative length of stay, physician claims and placements in extended care services) were obtained for the 12 months before and 10 years after the injury. Negative binomial and Poisson regressions were used to quantify associations between injury and long-term HSU. FINDINGS: Statistically significant differences in the rates of HSU existed between the injured and non-injured cohorts for the pre-injury year and every year of the follow-up period. After controlling for pre-injury HSU, the attributable risk percentage indicated that 38.7% of all post-injury hospitalizations (n = 25 183), 68.9% of all years spent in hospital (n = 1031), 21.9% of physician claims (n = 269 318) and 77.1% of the care home placements (n = 189) in the injured cohort could be attributed to being injured. CONCLUSION: Many people who survive the initial period following injury, face long periods of inpatient care (and frequent readmissions), high levels of contact with physicians and an increased risk of premature placement in institutional care. Population estimates of the burden of injury could be refined by including long-term non-fatal health consequences and controlling for the effect of pre-injury comorbidity.

Adolescent↗

How well do anatomical-based injury severity scores predict health service use in the 12 months after injury?

There is an acknowledged need for valid and reliable injury scores, suitable for use at the population level, which can accurately predict the long-term outcome of injury. The objective was to quantify the extent to which the abbreviated injury severity score (AIS) and the functional capacity index score (FCI) predict use of health services in the 12 months following an injury event. A cohort of injured people (ICD-9-CM 800-995) aged 18 - 64 years was identified from Manitoba hospital discharge abstracts from January 1988 to December 1991. For each member of the cohort whose injuries could be mapped to an abbreviated injury scale unique identifier, a maximum AIS (maxAIS) and a maximum FCI (maxFCI) were obtained. The cohort was linked with hospital discharge abstracts, physicians' claims and deaths from the population registry for the 12 months following injury. Negative binomial regression was used to model the relationships between the severity scores and the three outcome measures, while controlling for potential confounding variables. In total, 20 677 (97%) eligible cases were identified, of which 16 834 (81%) could be assigned a maxAIS and 15 823 (77%) a maxFCI. MaxAIS and maxFCI were significantly associated with total days in hospital following injury, but explained little of the variation in any of the health service use outcome variables (maxAIS, partial pseudo r2 ranging from < 0.001 to 0.041; and maxFCI, partial pseudo r2 ranging from < 0.001 to 0.018). It was concluded that anatomical damage is only partly responsible for long-term injury outcome. Additional variables would need to be included in predictive models of health outcomes of injury before these models could be reliable.

Activities of Daily Living↗

Indicators of injury burden: which types are the most important?

Injury indicators are used for monitoring the impact of injury prevention initiatives on the population burden of injury. The object of the present study was to identify the types of injury responsible for the major component of the population health burden of injury in a large cohort in Manitoba, Canada. Injury cases (ICD-9-CM 800-995) aged 18-64 years were identified from all Manitoba hospital data between 1988 and 1991. Morbidity data were obtained from hospital discharge abstracts 12 months prior to date of injury and for 12 months post-injury. Outcomes for individuals were calculated as the difference pre- and post-injury in hospital inpatient days. Death outcomes in the 12 months post-injury were obtained by linking the cohort with the population registry. Summed outcomes across the population were stratified into injury types based on the International Code of Diseases (ICD) code of the index injury. Outcomes were also stratified by injury severity score categories where the injury severity score was obtained using ICDMAP-90. When ranked by contribution to the cohort's cumulative hospital inpatient days in the 12 months post-injury, the six most common ICD subchapter groups accounted for 65% of the total inpatient days. These six injury types also accounted for 62% of the total number of deaths in this cohort in 12 months after injury. The suggested injury types to use as indicators of burden include fracture of the lower limb, fracture of the head and neck, poisonings, intracranial injury, fracture of the upper limb, and fracture of skull.

Adolescent↗

Long-term mortality following trauma: 10 year follow-up in a population-based sample of injured adults.

BACKGROUND: The aim of the study was to quantify trauma-related mortality in injured adults over 10 years postinjury. METHODS: A population-based matched cohort study used linked administrative data from Manitoba, Canada, to identify an inception cohort (1988-1991) of hospitalized trauma cases (ICD-9-CM 800-959.9) aged 18-64 years (n = 18,210) and a matched noninjured comparison group (n = 18,210). Mortality outcomes were obtained by linking the two cohorts with the Manitoba Population Registry for a period of 10 years postinjury. RESULTS: The adjusted all-cause mortality rate ratio (MRR) was 7.29 (95% CI 4.53-11.74) for the 60 days immediately postinjury. The MRRs ranged between 1.17 and 2.41 for the remainder of the 10 year follow-up period. The index injury was estimated to be responsible for 41% of all recorded deaths in the injured cohort. CONCLUSIONS: Estimates of the total mortality burden, based on the early inpatient period alone, substantially underestimates the true burden from injury.

Adult↗

Effects of acetyl-L-carnitine and myo-inositol on high-energy phosphate and membrane phospholipid metabolism in zebra fish: a 31P-NMR-spectroscopy study.

Acetyl-L-carnitine (ALCAR) and myo-inositol are reported to enhance motor activity in animal models; modulate membrane phospholipid metabolism (ALCAR and myo-inositol) and high-energy phosphate metabolism (ALCAR) back to normal; and be effective treatments of major depression in humans. Fish in general and zebra fish in particular present unique animal models for the in vivo study of high-energy phosphate and membrane phospholipid metabolism by noninvasive in vivo 31P NMR. This 31P NMR study of free-swimming zebra fish showed that both ALCAR and myo-inositol decreased levels of phosphodiesters and inorganic orthophosphate and increased levels of PCr in the fish. These findings demonstrate both ALCAR and myo-inositol modulate membrane phospholipid and high-energy phosphate metabolism in free-swimming zebra fish.

Acetylcarnitine↗

Appropriate indicators for injury control?

Indicators are valuable tools used to measure progress towards a desired health outcome. Increased awareness of the public health burden due to injury has lead to a concomitant interest in monitoring the impact of national initiatives that aim to reduce the size of the burden. Several injury indicators have now been proposed. This study examines the ability of each of the suggested indicators to reflect the nature and extent of the burden of non-fatal injury. A criterion validity, population-based, prospective cohort study was conducted in Brisbane, a sub-tropical Metropolitan City on the eastern seaboard of Australia, over a 12-month period between 1 January and 31 December 1998. Neither the presence of a long bone fracture nor the need for hospitalisation for 4 or more days were sensitive or specific indicators for 'serious' or major injury as defined by the 'Gold Standard' Injury Severity Score (ISS). Subsequent analysis, using other public health outcome measures demonstrated that the major component of the illness burden of injury was in fact due to 'minor' not serious injury. However, the suggested indicators demonstrated low sensitivity and specificity for these outcomes as well. The results of the study support the need to include at least all hospitalisations in any population-based measure of injury and not attempt to simplify the indicator to a more convenient measure aimed at identifying just those cases of 'serious' injury.

Adolescent↗

Randomized controlled study of digestive enzyme activity following trophic feeding.

UNLABELLED: A randomized, controlled, prospective study of 80 preterm infants of birthweight less than 1750 g requiring ventilatory support was performed. While ventilatory support was required group TF (39 infants) received trophic feeding (0.5-1 ml h(-1)) along with parenteral nutrition, whereas group C (41 infants) received parenteral nutrition alone. When ventilatory support was no longer required milk feeds were started in group C and then increased in both groups until full milk feeds were established. The ratio of lactase to sucrase activity (L:S ratio) was measured in aspirated proximal intestinal fluid on 3 occasions: immediately after ventilatory support was withdrawn (T0), 7 days later (T7) and 14 days later (T14). On the same 3 occasions faecal chymotrypsin activity was measured. The mean difference (95% confidence interval) L:S ratio was significantly higher in group TF at both T0 and T14, 1.8 (0.03, 3.57) and 0.78 (0.2, 1.35) U l(-1), respectively. There was no significant difference in faecal chymotrypsin concentration. CONCLUSION: Trophic feeding alters relative intestinal disaccharidase activity, probably by inducing lactase production, but has no effect on pancreatic chymotrypsin activity.

Chymotrypsin↗

Dose regimen for vancomycin not needing serum peak levels?

AIM: To determine the safety, efficacy, and need to measure peak serum vancomycin concentrations in a neonatal population using a standard vancomycin dosage regimen. METHOD: A total of 101 infants who were admitted to a regional neonatal intensive care unit and received vancomycin (15 mg/kg every 12 or 18 hours depending on postnatal age) were studied retrospectively. Infants who had been started on vancomycin before they were transferred to the unit were excluded. The proportion of infants was measured whose serum vancomycin concentrations were within a conservative therapeutic range of trough 5-10 mg/l, peak 20-40 mg/l, and a less conservative, but still safe, range of trough 5-12 mg/l, peak 15-60 mg/l. RESULTS: Trough concentrations of 5-10 mg/l were achieved by 46.5% of infants, and 5-12 mg/l by 55.4%. Peak concentrations of 20-40 mg/l were found in 83.2% of infants, and 15-60 mg/l in 99.0%. Highest peak concentration was 47.2 mg/l. Some 89.4% of infants with trough concentrations of 5-10 mg/l had a peak concentration of 20-40 mg/l. CONCLUSIONS: The vancomycin dosage regimen used in this study produces acceptable therapeutic serum vancomycin concentrations. Peak serum vancomycin concentrations do not need to be measured in neonates using this dosage regimen.

Anti-Bacterial Agents↗

Population based study of hospitalised fall related injuries in older people.

OBJECTIVE: This study aimed to identify the distribution of fall related injury in older people hospitalised for acute treatment of injury, in order to direct priorities for prevention. SETTING: A follow up study was conducted in the Brisbane Metropolitan Region of Australia during 1998. METHODS: Medical records of patients aged 65 years and over hospitalised with a fall related injury were reviewed. Demographic and injury data were analysed and injury rates calculated using census data as the denominator for the population at risk. RESULTS: From age 65, hospitalised fall related injury rates increased exponentially for both males and females, with age adjusted incidence rates twice as high in women than men. Fractures accounted for 89% of admissions, with over half being to the hip. Males were significantly more likely than females to have fractured their skull, face, or ribs (p<0.01). While females were significantly more likely than males to have fractured their upper or lower limbs (p<0.01), the difference between proportions of males and females fracturing their hip was not significant. Males were more likely than females (p<0.01) to have fall related head injuries (13% of admissions). Compared with hip fractures, head injuries contributed significantly to the burden of injury in terms of severity, need for intensive care, and excess mortality. CONCLUSIONS: The frequency and impact of hip fractures warrants continued emphasis in falls program interventions for both males and females to prevent this injury. However, interventions that go beyond measures to slow and protect against bone loss are also needed to prevent fall related head injuries.

Accidental Falls↗

Chronic myo-inositol increases rat brain phosphatidylethanolamine plasmalogen.

BACKGROUND: Oral myo-inositol (12--18 g/day) has shown beneficial effect in placebo-controlled studies of major depression, panic disorder, and obsessive compulsive disorder, and preliminary data suggest it also may be effective in bipolar depression. Evidence linking antidepressant activity to membrane phospholipid alterations suggested the examination of acute and chronic myo-inositol effects on rat brain membrane phospholipid metabolism. METHODS: With both (31)P nuclear magnetic resonance (NMR) and quantitative high-performance thin-layer chromatography (HPTLC; hydrolysis) methods, rat brain phospholipid levels were measured after acute (n = 20, each group) and chronic myo-inositol administration (n = 10, each group). With (31)P NMR, we measured myo-inositol rat brain levels after acute and chronic myo-inositol administration. RESULTS: Brain myo-inositol increased by 17% after acute myo-inositol administration and by 5% after chronic administration, as compared with the control groups. Chronic myo-inositol administration increased brain phosphatidylethanolamine (PtdEtn) plasmalogen by 10% and decreased brain PtdEtn by 5%, thus increasing the ratio PtdEtn plasmalogen (PtdEtn-Plas)/PtdEtn by 15%. Phosphatidylethanolamine plasmalogen levels quantified by (31)P NMR and HPTLC were highly correlated. The validity and reliability of the (31)P NMR method for phospholipid analysis were demonstrated with phospholipid standards. CONCLUSIONS: The observed alteration in the PtdEtn-Plas/PtdEtn ratio could provide insights into the therapeutic effect of myo-inositol in affective disorders.

Animals↗

Structure-function analysis of D9N and N291S mutations in human lipoprotein lipase using molecular modelling.

Lipoprotein lipase (LPL) plays a central role in lipid metabolism. The D9N and N291S mutations in the LPL gene are associated with elevated triglyceride and decreased HDL-cholesterol levels. Published in vitro expression studies suggest that these two mutations are associated with reduced LPL enzymatic activity. We sought to gain further insight on the impact of these two mutations on the LPL structure and function by molecular modelling techniques. Homology modelling was used to develop a three-dimensional (3D) structure of LPL from human pancreatic lipase. Two separate LPL models for the D9N and N291S substitutions were constructed and compared with the wild type LPL for differences in hydrophobicity, atomic burial, hydrogen bond pattern, and atomic mobility. In comparison to the wild type model, the 9N model was associated with significantly increased atomic mobility of its neighboring residues, but the catalytic site was not affected. The region near residue 9 in the upper part of the N-domain was considered a candidate site for protein-protein interaction. In the N291S model, alterations in H-bonds and constrained atomic mobility were among conformational changes in the region where the substitution had occurred. These are hypothesized to cause an increase in the rate of dissociation in LPL dimerization, subsequently affecting the LPL enzymatic activity. We also modelled the C-domain of apoCII, the obligatory cofactor of LPL, from 2D NMR data and docked the model with LPL to explore their interaction site. These docking experiments suggest that the C-domain of apoCII interacts with the interface of N- and C-domains of LPL and part of the lid structure that covers the catalytic site. In summary, we provide molecular modelling data on two well-known mutations in the LPL gene to help explain the published in vitro expression findings and propose a possible LPL-apoCII interaction site. Our data indicate that molecular modelling of LPL mutations could provide a valuable tool to understand the effects of a mutation on the structure-function of this important enzyme.

Amino Acid Sequence↗

Brain metabolic effects of acute nicotine.

(-)Nicotine acetylcholine receptors are located on both nerve cell bodies and synaptic terminals, are permeable to calcium, and function perhaps predominantly by facilitating the release of neurotransmitters and neuropeptides. The behavioral rewards from (-)nicotine and perhaps addiction appear to be related to dopamine release. 31P NMR analysis reveals subcutaneously administered (-)nicotine produces acute alterations in brain membrane phospholipid and high-energy phosphate metabolism of Fischer 344 rats. These metabolic responses to (-)nicotine could contribute to nicotine's behavioral effects.

Animals↗

Brain membrane phospholipid alterations in Alzheimer's disease.

Studies have demonstrated alterations in brain membrane phospholipid metabolite levels in Alzheimer's disease (AD). The changes in phospholipid metabolite levels correlate with neuropathological hallmarks of the disease and measures of cognitive decline. This 31P nuclear magnetic resonance (NMR) study of Folch extracts of autopsy material reveals significant reductions in AD brain levels of phosphatidylethanolamine (PtdEtn) and phosphatidylinositol (PtdIns), and elevations in sphingomyelin (SPH) and the plasmalogen derivative of PtdEtn. In the superior temporal gyrus, there were additional reductions in the levels of diphosphatidylglycerol (DPG) and phosphatidic acid (PtdA). The findings are present in 3/3 as well as 3/4 and 4/4 apolipoprotein E (apoE) genotypes. The AD findings do not appear to reflect non-specific neurodegeneration or the presence of gliosis. The present findings could possibly contribute to an abnormal membrane repair in AD brains which ultimately results in synaptic loss and the aggregation of A beta peptide.

Aged↗

Trophic feeding of the preterm infant.

Trophic feeding is the practice of feeding minute volumes of enteral feeds in order to stimulate the development of the immature gastrointestinal tract of the preterm infant This paper reviews the randomized controlled studies that have examined the physiological and clinical responses to trophic feeding of the preterm infant. Trophic feeding alters gastrointestinal disaccharidase activity, hormone release, blood flow, motility and microbial flora. Clinical benefits appear to include improved milk tolerance, greater postnatal growth, reduced systemic sepsis and shorter hospital stay. There is currently no evidence of any adverse effects following trophic feeding.

Digestive System Physiological Phenomena↗

Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids.

OBJECTIVE: There is evidence linking affective disorders and their treatment to alterations in membrane phospholipid metabolism, the phosphatidylinositol (PtdIns) second messenger cycle and brain excitatory and inhibitory amino acids. This study examines lithium effects on rat brain metabolites associated with the above systems and their reversal by myo-inositol. METHODS: Thirty rats were treated for 14 days with i.p. lithium, saline or lithium plus myo-inositol. 1H, 31P and 7Li NMR were used to measure brain metabolites. RESULTS: Lithium, administered alone or with myo-inositol, resulted in brain lithium concentrations of approximately 0.6 microM/gram brain tissue. Brain myo-inositol was unchanged when lithium was co-administered with myo-inositol. Lithium increased brain inositol-1-phosphate (I1P) by 98% compared with saline and this effect was not attenuated by the addition of myo-inositol. Lithium treatment decreased phosphatidylserine (PtdSer) and PtdIns by 3% and 8%, respectively. Lithium also decreased taurine levels by 8% and increased aspartate levels by 9%. The above effects of lithium on PtdSer, PtdIns and taurine were attenuated or abolished by the co-administration of myo-inositol. CONCLUSIONS: Lithium alters levels of key membrane phospholipids and appears to affect the balance between inhibitory and excitatory amino acids in rat brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.

Amino Acids↗