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Biomedical subjects

E Milne

Publications and source records attributed to E Milne.

At least 37 records · Page 2Linked to original sources

Direct measurement of sun protection in primary schools.

BACKGROUND: "Kidskin" is an intervention study involving children at 33 primary schools in Perth, Western Australia. This study includes measurement of changes in implementation of schools' sun protection policies. This paper reports on measurement of observable aspects of sun protection. METHODS: Hat use was assessed from videos of children in the playground. Shade use was measured using UVR-sensitive polysulfone badges worn by a random sample of children. Shade provision was measured from aerial photographs of the schools. Principals were surveyed about school policies and practices. RESULTS: Eighty-seven percent of children wore a hat during lunch time at school, although only 14% wore the most protective styles of hats. The mean proportion of ambient UVR exposure received by Year 1 children was 15.5%; children spent less time in the sun on sunnier days. On average, 14.5% of the playground was shaded; this was not associated with children's sun exposure. Correlations between these results and the principals' estimates were poor. CONCLUSIONS: Children should be encouraged to wear more protective styles of hats and to avoid sun exposure, even on less sunny days during spring and summer. Principals' estimates of shade provision and children's sun protection behavior at school are of little value.

Analysis of Variance↗

The quantification of mortality resulting from the regular use of illicit opiates.

UNLABELLED: AIMS/DESIGN: Estimates of mortality associated with illicit opiate use provide useful information to those directing and monitoring local, national and international policies and programmes. Most studies investigating the association have, however, been small with imprecise estimates of increased mortality. The current study combines data from a number of international studies in a meta-analysis to estimate more precisely mortality associated with illicit opiate use. Because HIV infection among injecting drug users differs dramatically between countries and localities, we excluded studies where AIDS was a major contributor to mortality. Studies were included only where AIDS-specific mortality accounted for less than 2% of total mortality. FINDINGS: Our results show a mortality rate for people regularly using illicit opiates, which is more than 13 times greater than that observed for the general community. It is estimated that 9.4% of total mortality in Australians aged 15-39 years of age can be attributed to regular use of illicit opiates. Application of this aetiological fraction to Australian mortality data for 1992 indicate that approximately 401 male and 161 female deaths occurred as a result of opiate use. This represents some 15,429 and 6261 person-years of life lost (to age 70) for males and females, respectively. CONCLUSIONS: The mortality rate for illicit opiate users is approximately 13 times greater than for the general population. The large number of years of life lost is reflective of the relatively young population (15-39 years of age) in which opiate-related mortality occurs. Relative risk estimates can also be applied to data on the prevalence of illicit opiate use in other countries to produce locally based aetiological fractions and estimates of person-years of life lost.

Adolescent↗

Responses in the absorptive phase in muscle and liver protein synthesis rates of growing rats.

The effect of time after beginning of a meal (30, 60, 90 and 120 min) on liver and gastrocnemius muscle protein synthesis was tested in growing male rats using the large dose technique, based on a 10 min exposure to [15N]phenylalanine. The fractional synthesis rate was estimated from the ratio between the atom percent excess of tissue protein-bound and free labelled phenylalanine. The latter was measured by gas chromatography mass spectrometry using the tertiary-butyldimethylsilyl amino acid derivatives. The protein-bound phenylalanine of gastrocnemius muscle was separated from the other amino acids using preparative amino acid chromatography and then oxidised to N2 in an automated carbon-nitrogen Roboprep (CN) combustion module attached to a continuous flow isotope ratio mass spectrometer (IRMS), with m/z ions 28 and 29 monitored. The protein-bound phenylalanine from liver was separated by a gas chromatograph attached to a sample preparation module and an isotope ratio mass spectrometer (GC C-IRMS), with again m/z ions of 28 and 29 monitored. The following results were obtained: the daily fractional protein synthesis rates (ks) in gastrocnemius muscle and liver were 13.9% and 65.6% respectively, in 12 h fasted 145 g rats. These ks increased within 30 min after ingestion of meal to 14.9% and 91.8% for muscle and liver, respectively, and remained at these values for the next 90 min (14.6% and 87.4% at 60 min, and 14.3% and 88.6% at 120 min after the beginning of feeding). It was concluded that measurement of protein synthesis rates characteristics for the absorptive phase can be undertaken in a period from thirty minutes to two hours after start of a meal, without significant changes in the ks values.

Amino Acids↗

The use of observational methods for monitoring sun-protection activities in schools.

Evaluation of health promotion interventions aimed at behavioural or environmental change involves assessing change that occurs as a result of the program. Direct observational methods can be used for this purpose and this paper describes three such methods that we pilot tested for use in a 5-year intervention study aimed at reducing sun exposure in primary school children. (1) Monitoring 'No hat, no play' policies. This method involved video taping children in selected school play areas during lunch time and analysing the content of the videos to assess the proportion of children wearing various types of hats. (2) Assessing shade provision in the playground. This method involved taking aerial photographs of each school and using them to estimate the proportion of shade in play areas available to children at lunchtime. (3) Shade use. This involved children wearing polysulphone film badges to measure the amount of UV-B exposure they received during one lunch period, relative to the total possible dose registered on index badges. Each method was implemented successfully, and we demonstrated that the video and aerial photography methods produced highly reproducible results and that all three methods were feasible. These three methods will be used in our intervention study to assess longitudinal change in schools' sun-protection policy and practice.

Child↗

Nitric oxide synthesis in patients with infective gastroenteritis.

BACKGROUND: There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis. AIMS: To determine whether this is due to nitric oxide (NO) production via the L-arginine/NO pathway. METHODS: Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mg L-[(15)N](2)-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [(15)N:(14)N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. RESULTS: Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) micromol compared with 2594 (234) micromol in the control group (p<0.001). Thirty six hour urinary [(15)N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) etamol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [(15)N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [(15)N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) etamol/mmol; p<0.001). CONCLUSION: Results show notably enhanced nitrate synthesis due to increased activity of the L-arginine/NO pathway in patients with infective gastroenteritis.

Adult↗

Commissioning. Share options.

A system of effective commissioning will be crucial to the reorganised NHS. Any system must combine flexibility for primary care groups with financial stability for trusts. A four-part funding stream for PCGs could be effective.

Budgets↗

Assessing the relationship between maternal opiate use and antepartum haemorrhage.

UNLABELLED: AIMS/DESIGN: Assessment of the association between the regular use of opiates by women during pregnancy and antepartum haemorrhage has been made difficult by the low prevalence of these conditions observed in clinical settings. As a consequence, most published studies lack statistical power due to the small number of cases. We combined all suitable published data in a meta-analysis to assess the association more accurately. FINDINGS: Meta-analysis produced a pooled estimate of the crude odds ratio for antepartum haemorrhage in relation to maternal opiate use of 2.33 (95% CI 1.32-4.30). CONCLUSIONS: This odds ratio estimate is consistent with a moderately strong association. Studies included did not adjust for possible confounders (e.g. prenatal care, cocaine or tobacco), so confounding is likely to account for at least some of the observed effect. The relative consistency of results from studies included in the meta-analysis that were conducted in different countries and at different times adds to the strength of the evidence for an association between opiate use and antepartum haemorrhage. Well designed studies are urgently required to assess the independent effects of different types and patterns of maternal opiate use and confounders such as cigarette smoking, illicit cocaine use and antenatal care on antepartum haemorrhage.

Female↗

Assessing the relationship between maternal opiate use and neonatal mortality.

UNLABELLED: We undertook a number of meta-analyses to estimate more precisely the relationship between neonatal mortality and use of opiates in three groups of women. First, women who continued to use illicit heroin throughout pregnancy; secondly, women stabilized on methadone at the time of conception or shortly after and thirdly, women who use heroin well into pregnancy with late entry into methadone treatment, or who continued to use illicit heroin during pregnancy while receiving methadone. FINDINGS: The pooled estimates of the relative risks of neonatal mortality for separate heroin and methadone use were both near unity: 1.47 (95% CI 0.88-2.33) and 1.75 (95% CI 0.60-4.59), respectively. The result for heroin may be due to the inclusion in the meta-analysis of a particularly large study, which, unlike the two other smaller studies included found a relative risk near unity. When this study was excluded from the meta-analysis the pooled estimate of the relative risk of neonatal mortality for heroin use was 3.27 (95% CI 0.95-9.60). In contrast to the results for use of methadone only, the pooled relative risk associated with heroin and methadone use was 6.37 (95% CI 2.57-14.68). CONCLUSIONS: The increased relative risk for neonatal mortality associated with women using heroin and methadone during pregnancy, compared to those stabilized on methadone, is probably due to the chaotic and high-risk life-style associated with illicit heroin use and not solely to the use of heroin and methadone per se. It is recommended tht women who use heroin well into pregnancy with late entry into methadone treatment, or who continue to use illicit heroin during pregnancy while receiving methadone, receive special attention over and above that provided to women stabilized on methadone.

Female↗

Urea recycling in sheep: effects of intake.

The effect of intake on urea production, entry into the digestive tract and return of N to the ornithine cycle was studied in four sheep. Each sheep received 0.6, 1.2 and 1.8 x estimated maintenance energy intake quantities of grass pellets for 9 d. After 4 d of adjustment, N balance measurements were conducted between days 5 and 8. From day 7 to day 9 animals were continuously infused, via the jugular vein, with [15N15N]urea and three urine samples were collected at approximately 2 h intervals 48-54 h after the start of infusion. Total urea and enrichments of [15N15N]- and [14N15N]urea in the urine samples were determined. Urea production was calculated from the isotopic dilution of [15N15N]urea and entry into the gastrointestinal tract (GIT) obtained from the difference between this and urinary urea elimination. Urea which enters the GIT undergoes hydrolysis to liberate NH3 which may be reabsorbed and enter the ornithine cycle in which case the product is [14N15N]urea, based on the probabilities of labelled and unlabelled N providing ureagenic precursors. The quantity of urea-N which returns to the ornithine cycle from the GIT can thus be calculated. Existing models based on this approach yield overestimates of the fate of individual urea molecules due to a failure to allow for multiple recycling of [14N15N]urea species through the GIT. Refinements introduced to cover this resulted in a 33-48% reduction in calculated return of label for the current study. The present model also predicted that 95% of the label movements across the GIT could be accommodated by three or fewer entries and returns of urea-N and 99% by recycling for a maximum of six occasions. Urea-N production increased with intake (P < 0.001) and exceeded digestible N values at all intakes. Urea which entered the digestive tract, both in absolute terms (P < 0.001) and as a proportion of production (0.62, 0.69, 0.73; P = 0.027), increased with intake. The proportion of entry into the digestive tract which was returned to the ornithine cycle remained reasonably constant (0.37-0.41) across all intakes but the absolute amount increased (5.6, 9.2 and 15.0 g N/d; P < 0.001) with intake. If allowance is included for losses of 15N in faeces then the approach offers a relatively simple means of estimating anabolic reuse of urea by digestive tract micro-organisms and can complement data obtained from the technically more demanding arterio-venous and multiple-isotope techniques used hitherto.

Animals↗

Evidence for a difference in nitric oxide biosynthesis between healthy women and men.

There is indirect evidence for a gender difference in nitric oxide (NO) synthesis from vascular endothelium. The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-[15N]2-guanidino arginine. Twenty-four healthy volunteers (13 men aged 22 to 40 years and 11 women aged 23 to 42 years) participated in this study. No subjects were receiving any medication. Women were studied between the 7th and 14th days of their menstrual cycles. Arterial blood pressure was measured oscillometrically, and 1.13 micromol L-[15N]2 arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours in separate 12-hour periods. Urinary 15N/14N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. Mean 36-hour urinary 15N nitrate excretion was greater in women than in men (2111+/-139 versus 1682+/-87 etamol; P<0.05). Furthermore, total urinary 15N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects (coefficient of correlation, 0.47; P=0.022). The present data show that whole-body production of NO is greater in healthy premenopausal women than in men under ambulatory conditions. The cellular origin of NO measured in this study is unknown, but differences in endothelial production could underlie differences in vascular function between men and women.

Adult↗

Estimation of energy expenditure in free-living red deer (Cervus elaphus) with the doubly-labelled water method.

Energy expenditure was estimated using the doubly-labelled water (DLW) method in summer in five free-living adult, non-pregnant, non-lactating, red deer (Cervus elaphus) hinds (weight 107.3 (SE 0.9) kg; age 6 (SE 1) years) on lowland pasture under typical farming conditions. Climatic conditions were monitored throughout the experiment. Errors due to 2H losses in CH4 and faeces were calculated from previous estimates of stoichiometries. CH4 production, fractionated water loss, urinary N and O2 consumption were estimated using an iterative approach. The water flux (rH2O) in these animals consuming only fresh grass was 12 (SE 0.5) kg/d, the CO2 production (rCO2) was 1271 (SE 40) litres/d and the mean energy expenditure was 25 (SE 0.8) MJ/d. There were no significant differences in the isotope distribution spaces and flux rates, rH2O, rCO2 or energy expenditure using the multi-point or two-point approaches to calculation. The DLW-derived energy expenditure of 25 MJ/d is approximately 20% higher than the recommended intake of 21 MJ/d for adult hinds kept outdoors (Adam, 1986) and, at 757 kJ/kg0.75 per d, one third higher than the value of 570 kJ/kg0.75 per d for stags penned indoors (Key et al. 1984).

Animals↗

Basal nitric oxide synthesis in essential hypertension.

BACKGROUND: There is indirect evidence that nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. The aim of this study was to estimate more directly NO production in patients with untreated essential hypertension by measurement of synthesis of inorganic nitrate, which is the end product of NO oxidation in humans. Two separate studies were undertaken in patients with hypertension and appropriate healthy controls. METHODS: In the first study, ten patients and 13 controls were given a diet containing 82 mumoles nitrate per day for 2 days, with urinary and plasma nitrate measurement and 24 h ambulatory blood pressure monitoring on the 2nd day. In the second study, 11 patients and 11 controls were studied in the postabsorptive state; a bolus of 200 mg L[15N]2 arginine was administered intravenously over 10 min. 24 h ambulatory blood pressure monitoring was done and complete urine collections were made for the next 36 h. FINDINGS: In the first study, 24 h urinary nitrate excretion was lower in the hypertensive patients than in the control group (mean 450 [SEM 37] vs 760 mumoles [77] per 24 h; p < 0.001). There was an inverse correlation between average mean daytime ambulatory blood pressure and nitrate excretion (p = 0.007; r2 = -0.73). In the second study, mean 36 h urinary 15N nitrate excretion was significantly lower in the hypertensive than in the control group (1313 [50] vs 2133 [142] pmoles; p < 0.001). There was an inverse correlation also between average mean daytime ambulatory blood pressure and 24 h urinary 15N nitrate excretion expressed per mmole of creatinine (p = 0.002, r2 = -0.59). In addition, total urinary 15N nitrate excretion in the hypertensive group was significantly higher in women than in men (285 [16] vs 198 [14] micrograms 15N nitrate per kg; p = 0.026). INTERPRETATION: These data suggest that whole-body NO production in patients with essential hypertension is diminished under basal conditions. The origin of the NO we measured is not known, and we cannot tell whether the impaired synthesis is primary or secondary to a rise in blood pressure.

Adult↗

Measurement of NO synthesis in humans by L-[15N2]arginine: application to the response to vaccination.

Induction of nitric oxide (NO) synthesis is a key element of the inflammatory response in humans. We describe a sensitive gas isotope ratio mass spectrometric (GIRMS) method for measuring urinary [15N]nitrate production during intravenous infusion of L-[guanidino-15N2]arginine and its application to investigate the effects of a controlled inflammatory stimulus, typhoid vaccination, on NO synthesis in humans. Intravenous infusion of L-[15N2]arginine at 5-12 mumol.kg-1.h-1 for 24 h in three subjects was used to determine arginine and nitrate pool kinetics. Eight subjects received primed constant infusion of 2.5 mumol.kg-1.h-1 of L-[15N2]arginine for 12 h once before and again after typhoid vaccination. NO synthesis was calculated from 15N enrichment of plasma arginine and urinary nitrate, measured by gas chromatography mass spectrometry and GIRMS, respectively, and total urinary nitrate excretion. Baseline NO synthesis was 298 +/- 44 nmol.h-1.kg lean body mass-1, representing 0.41% of arginine flux. After vaccination, NO synthesis (267 +/- 77 nmol.h-1.kg-1) was not increased (P = 0.18), despite demonstration of an acute phase response. Typhoid vaccination is not accompanied by accelerated NO synthesis.

Adult↗

Use of feces to estimate isotopic abundance in doubly labeled water studies in reindeer in summer and winter.

The reliance on samples of blood or urine to estimate isotopic abundance in studies of energy metabolism using the doubly labeled water method has restricted application of the technique to animals that are either tame or easy to catch. This is generally not the case with large, free-ranging wild mammals. The use of feces as a source of body water in which to measure the concentration of isotopic markers was investigated in four female reindeer in summer and in winter. (2)H2O and H2(18)O were injected to approximately 160 parts per million excess. Samples of plasma and feces were then collected simultaneously for up to 456 h. Both isotopes were equilibrated with body water at 8 h postdose. There were no significant differences by animal between dilution spaces, rate constants, rates of CO2 production, and total energy expenditure (TEE) calculated based on samples of plasma or feces in any trial. Mean TEE was 3.557 W/kg (SD 0.907, n = 4) in summer and 1.865 W/kg (SD 0.166, n = 4) in winter.

Animals↗

Assessing the relationship between maternal cocaine use and abruptio placentae.

Abruptio placentae during pregnancy can result in significant morbidity and mortality to both mother and infant. A comprehensive literature search of publications from 1966 to April 1995 identified 11 studies on the association between maternal cocaine use and abruptio placentae. Their results were combined in a meta-analysis. The pooled odds ratio for abruptio placentae and maternal cocaine use was 3.92 (95% confidence interval 2.77-5.46). The strength and consistency of the association, its biological plausibility and the results of experimental studies in animals all suggest that cocaine use during pregnancy causes abruptio placentae.

Abruptio Placentae↗