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Biomedical subjects

P J Graham

Publications and source records attributed to P J Graham.

At least 19 recordsLinked to original sources
PubMed2003

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.

Adolescent↗
PubMed2001

Age at diagnosis, glycaemic control and the development of retinopathy in a population-based cohort of Type 1 diabetic subjects in Canterbury, New Zealand.

The aim was to determine the relationship between age at diagnosis, glycaemic control and the development of retinopathy in a population-based cohort of Type 1 diabetic subjects. At 1 January 1984, there were 286 individuals with Type 1 diabetes (and age of onset<20 years) on the Canterbury, New Zealand population register who had at least 2 prospective HbA(1c) readings (from 1 January 1984). Of these, 107 already had retinopathy. Of the 179 subjects without retinopathy at baseline 63 developed retinopathy during follow-up. After controlling for duration of diabetes (in the whole group), age at diagnosis was found to be a significant predictor of HbA(1c) level (P=0.001), with higher (mean+/-SD) baseline HbA(1c) in the 10-14 age group (7.95+/-2.14%), compared with (7.62+/-1.77%) in the <10 year group and (7.39+/-2.57%) in the >14 year group. The major predictors of retinopathy (in those without retinopathy at baseline), however were duration of diabetes (mean time to development of retinopathy decreases by 14% (95% CI 10-17%) for each year), baseline HbA(1c) (for each unit increase, mean time to development of retinopathy decreased by 23% (95%CI 13-32%) and HbA(1c) slope (average annual change). Peri-pubertal age at diagnosis (10-14 years) did not influence the time to onset of retinopathy over and above that attributed to duration of diabetes and glycaemic control.

Adolescent↗
PubMed2000

Vitamin A supplementation for preventing morbidity and mortality in very low birthweight infants.

BACKGROUND: Vitamin A is necessary for normal lung growth and the ongoing integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease. Several studies have been undertaken to assess whether vitamin A supplementation beyond that routinely given in multivitamin preparations can reduce the incidence of this outcome. OBJECTIVES: To assess the benefit of supplementation with vitamin A in very low birthweight infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, Cochrane Controlled Trials Register, and Science Citation Index. The reference lists of relevant trials, recent issues of paediatric and nutrition journals, abstracts and proceedings from relevant conferences in the English language were hand searched. SELECTION CRITERIA: Randomised controlled trials which compared the effects of supplemental vitamin A with standard vitamin A regimes in infants with birthweight </=1500g, and which reported clinical outcomes (death, chronic lung disease or bronchopulmonary dysplasia) and/or vitamin A concentrations were considered for the review. DATA COLLECTION AND ANALYSIS: Data on mortality, requirement for supplemental oxygen at one month of age and at 36 weeks post-menstrual age, retinopathy of prematurity and nosocomial sepsis were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Six eligible trials were identified, one having a much larger sample size than the others combined. The meta-analysis suggests supplementation with vitamin A results in benefit in terms of reducing oxygen requirement at 36 weeks post-menstrual age [summary RR 0.85 (0.73, 0.98), RD -8.5% (-15.9, -1.1), NNT 11.8 (6.3, 90.9)] and trends towards reduction in death or oxygen requirement at 36 weeks post-menstrual age [summary RR 0.89 (0.79, 1.00)], oxygen use in survivors at one month of age [summary RR 0.93 (0.86, 1.01)], and death or oxygen requirement at one month of age [summary RR 0.93 (0. 86, 1.00)]. Meta-analysis of the two studies which reported on retinopathy of prematurity suggests a trend towards reduced incidence in vitamin A supplemented infants. REVIEWER'S CONCLUSIONS: Supplementing very low birthweight infants with vitamin A is associated with a reduction in oxygen requirement amongst survivors at 36 weeks post-menstrual age. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections should be assessed in a further trial.

Dietary Supplements↗
PubMed2000

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Double-Blind Method↗
PubMed1998

Lipid but not glycaemic parameters predict total mortality from type 2 diabetes mellitus in Canterbury, New Zealand.

A cohort of 447 subjects with Type 2 diabetes mellitus (208 male, 239 female; age range 30-82, median 62 years; and of predominantly European origin) was characterized in a clinic survey in 1989. Individual status (dead or alive) at 1 June 1995 was ascertained. Mortality rates were compared with the general New Zealand population by calculating standardized mortality ratios (SMR) and the hazard ratio (HR) of prognostic factors evaluated with Cox's proportional hazards model. At 6 years, 289 subjects were confirmed as alive and 133 as dead; only 25 were untraceable. Six-year survival for the cohort was 70% (95% CI 66-74). SMR was 2.53 (95% CI 1.99-2.68) for the female cohort and 2.03 (95% CI 1.60-2.59) for the male cohort. Factors assessed at baseline (1989) that were independently prognostic of total mortality included age, male sex, pre-existing coronary artery disease (CAD) (HR 2.2, 95% CI 1.5-3.3) and plasma cholesterol (HR for 1.4 mmol l(-1) change: 1.49, 95% CI 1.2-1.9). HDL-cholesterol was protective in women (HR for 0.4 mmol l(-1) change: 0.72, 95% CI 0.51-1.00) but not men. Glycated haemoglobin was not a significant predictor of total mortality. Predictors of CAD mortality (in those subjects free of CAD in 1989) included plasma cholesterol (HR for 1.4 mmol l(-1) change: 1.86 95% CI 1.20-2.89), glycated haemoglobin (HR for 1.8% change: 1.9 95% CI 1.04-3.47), male sex, peripheral vascular disease, and smoking. There is therefore increased mortality in Type 2 diabetic subjects in Canterbury, New Zealand. HDL-cholesterol is protective against total mortality in females.

Accidents↗
PubMed1998

Clinical and biochemical outcomes of type 2 diabetes mellitus in Canterbury, New Zealand: a 6-year cohort study.

There is a paucity of data regarding outcomes of Type 2 diabetes mellitus. A cohort of 447 Type 2 diabetic subjects (208 male, 239 female; age range 30-82 years, median 62 years; and of predominantly European origin) was characterised in a clinic survey in 1989. Individual status (dead or alive) at 1 June 1995 was ascertained. At 6 years, 289 subjects were confirmed as alive and 133 as dead--only 25 were untraceable. Of those subjects identified as alive, follow-up clinical and biochemical data were obtained for 253 (87.5%) individuals. In those subjects, glycated haemoglobin deteriorated from 63.1 +/- 18.7 mmol/mol haem in 1989 to 71.7 +/- 24.4 in 1995, P < 0.0001. An increased prevalence of retinopathy was evident at 6-year follow-up, 59.7% cases in 1995 compared with 39.5% in 1989, P < 0.001. Similarly there was an increased prevalence of coronary artery disease (CAD) (33.6 vs 18.2% of cases), albuminuria (26.5 vs 19% of cases; P < 0.001), and hypertension (71.5 vs 54.9% of cases; P < 0.001) in 1995 vs 1989, respectively. Multiple logistic regression analysis showed that glycated haemoglobin (odds ratio (OR) for 18 mmol/mol haem change, 1.78; 95% CI, 1.15-2.85), hypertension (OR, 3.33; 95% CI, 1.40-8.41) and known duration of diabetes (OR for 7 year change, 2.12; 95% CI, 1.24-3.80) were predictors for development of retinopathy. There is therefore a deterioration in glycaemic control in Type 2 diabetes over 6 years and an increased prevalence of complications that present strategies in a multidisciplinary specialist diabetes clinic are unable to prevent on a sustainable basis.

Adult↗
PubMed1998

Plasma vitamin A levels in the very low birthweight infant--relationship to respiratory outcome.

OBJECTIVE: To examine the association between plasma vitamin A levels and outcome measures in very low birthweight (VLBW) infants, including meta-analysis of all observational studies. DESIGN: A prospective observational longitudinal study of plasma vitamin A levels measured in the cord blood; maternal blood in the first 48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age and correlated with antenatal and postnatal events. A meta-analysis of all published observational studies on the association of vitamin A with respiratory outcome in the VLBW infant was undertaken. PATIENTS: Fifty-seven infants (88% of all eligible) VLBW infants (< 1500 g) admitted from January through October 1993 to one of two regional neonatal intensive care units in the South Island of New Zealand. RESULTS: Exposure to antenatal steroids led to a significant increase in infant cord plasma vitamin A levels (P = 0.003), but no influence on infant plasma vitamin A levels at any other time. Exposure to postnatal steroids produced a significant rise in infant plasma vitamin A levels between 7 and 28 days (P = 0.008). After controlling for gestational age, antenatal and postnatal steroid exposure, low vitamin A levels at 48 h increased the risk of developing chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19-5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On combining our results in meta-analysis with those of other published prospective observational studies, infants with chronic lung disease had lower plasma vitamin A levels at all times. CONCLUSIONS: Our results support an association between low plasma vitamin A levels and adverse outcome in the VLBW infant.

Chronic Disease↗
PubMed1998

Modification of U6 spliceosomal RNA is guided by other small RNAs.

The vertebrate spliceosomal snRNAs are highly modified by pseudouridylation and 2'-O-methylation. We have identified novel conserved small RNAs that can direct addition of two methyl groups in U6 snRNA, at A47 and C77. These guide RNAs, mgU6-47 (methylation guide for U6 snRNA residue 47) and mgU6-77 contain boxes C, C', D, and D' and associate with fibrillarin. Each RNA can form a duplex with U6 snRNA positioning A47 and C77 for 2'-O-methylation. The antisense element of mgU6-77 can also position C2970 of 28S rRNA for 2'-O-methylation. Depletion of mgU6-77 from Xenopus oocytes prevents 2'-O-methylation of both C77 in U6 and C2970 in 28S; methylation can be restored by injecting in vitro transcribed mgU6-77. Thus, mgU6-77 appears to function in the 2'-O-methylation of two distinct classes of cellular RNA, snRNA, and rRNA.

Animals↗
PubMed1995

Imidocarb residues in edible bovine tissues and in vitro assessment of imidocarb metabolism and cytotoxicity.

Imidocarb residues in liver and muscle were measured by HPLC after a single therapeutic dose to cattle (3 mg imidocarb dipropionate kg-1). Imidocarb and 7-ethoxycoumarin metabolism were compared in three different in vitro systems prepared from bovine liver: cultures of hepatocyte monolayers, precision-cut liver slices, and microsomes. The potential hepatotoxicity of imidocarb residues was tested on hepatocyte monolayers and assessed using the neutral red and lactate dehydrogenase leakage assays. The concentration of imidocarb (mean +/- SD) decreased between days 14 and 224 after treatment from 5.40 +/- 0.61 to 0.12 +/- 0.01 and from 1.05 +/- 0.31 to 0.06 +/- 0.02 microgram g-1 in liver and muscle, respectively. The depletion kinetics of imidocarb fitted a two-compartment model with alpha- and beta-phase half-lives of 31.7 and 48.5 days in liver and 34.9 and 120.7 days in muscle, respectively. Imidocarb metabolites were not detected in any in vitro system. 7-Ethoxycoumarin metabolism was found in all in vitro systems; the predominant metabolite produced by hepatocyte and liver slice cultures was umbelliferone glucuronide. Cytotoxicity of imidocarb (100 microM) to hepatocyte monolayers was maximal after 72 hr treatment and dose-dependent above 10 microM imidocarb. It is most likely that the hepatotoxicity of imidocarb is caused by the parent compound, because no evidence for imidocarb metabolism was found.

Animals↗
PubMed1995

The relationship of selenium status to respiratory outcome in the very low birth weight infant.

OBJECTIVE: To examine the relationship between plasma and erythrocyte selenium and glutathione peroxidase (GPx) levels in premature infants and outcome measures. DESIGN: Prospective observational longitudinal study. SETTING: Two regional neonatal intensive care units in the South Island of New Zealand, an area with low soil selenium. PATIENTS: Seventy-nine infants with birth weights less than 1500 g or gestation less than 32 weeks admitted within 48 hours of birth from November 1992 through November 1993. MAIN OUTCOME MEASURES: Oxygen requirement at 28 days (chronic lung disease), or 36 weeks postmenstrual age and for all or most of the time from birth (bronchopulmonary dysplasia), total days in oxygen, retinopathy of prematurity, periventricular hemorrhage, or ventricular dilatation. RESULTS: Initial infant plasma selenium and GPx levels were about two thirds of maternal levels and fell a further 30% in 28 days. In contrast to adults, there was a poor correlation in infant plasma between selenium and GPx at birth and 28 days. Plasma selenium at 28 days was significantly lower in infants with chronic lung disease and bronchopulmonary dysplasia. After controlling for gestational age and age when fully fed orally, 28-day plasma selenium was significantly associated with the log of total days of oxygen requirement, each drop of 0.1 mumol/L in 28-day selenium being associated with a 58% increase in days of oxygen dependency. No significant associations of other parameters of selenium status and respiratory outcome were found, and there were no significant associations of any parameters of selenium status with other outcome measures. CONCLUSIONS: This study demonstrates for the first time in human infants that low plasma selenium levels are significantly associated with an increased respiratory morbidity. Whether selenium deficiency is etiologically important in determining the respiratory outcome or the result of sickness in the infant should be investigated in a randomized, controlled trial.

Bronchopulmonary Dysplasia↗
PubMed1994

The prognostic significance of urinary albumin in Polynesians with non-insulin-dependent diabetes.

Polynesian (59 Maori and 30 Pacific Island) patients were identified from two diabetes clinic registers and followed for a mean of 4.8 years, in order to determine the prognostic significance of urinary albumin excretion. Events were defined as death or entry onto a renal replacement programme. Fourteen events occurred during the period of follow-up. Urinary albumin/creatinine ratio was treated as a continuous variable in a proportional hazards analysis. A 10-fold increase in albumin/creatinine ratio was associated with a 5-fold increase in the risk of an event (95% C.I. = 2.05-12.09). In conclusion, elevated urinary albumin/creatinine predicted mortality and renal morbidity in Maori and Pacific Island patients with non-insulin-dependent diabetes.

Albuminuria↗
PubMed1994

Paediatrics and child psychiatry: past, present and future.

The historical development of the relationship between paediatrics and child psychiatry is outlined and the closer working relationships between the two disciplines over the past 30 years are noted. Various ways in which child psychiatrists can contribute to paediatric practice are described, as well as the degree to which paediatricians can contribute to an understanding of child psychiatric disorders. It is suggested that new developments in paediatric practice and an increase in interest in genetic and brain mechanisms in child psychiatric disorders, will increase the need for collaboration between the two specialties.

Child↗
PubMed1993

Effects of a few food diet in attention deficit disorder.

Seventy-eight children, referred to a diet clinic because of hyperactive behaviour, were placed on a 'few foods' elimination diet. Fifty nine improved in behaviour during this open trial. For 19 of these children it was possible to disguise foods or additives, or both, that reliably provoked behavioural problems by mixing them with other tolerated foods and to test their effect in a placebo controlled double blind challenge protocol. The results of a crossover trial on these 19 children showed a significant effect for the provoking foods to worsen ratings of behaviour and to impair psychological test performance. This study shows that observations of change in behaviour associated with diet made by parents and other people with a role in the child's care can be reproduced using double blind methodology and objective assessments. Clinicians should give weight to the accounts of parents and consider this treatment in selected children with a suggestive medical history.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Developments in occupational health and safety qualifications.

Standards of competence for health and safety practitioners are being developed by the Occupational Health and Safety Lead Body (OHSLB) within the overall context of the national changes in vocational training. These changes focus on the development of National Vocational Qualifications (NVQs) and Scottish Vocational Qualifications (SVQs).

Occupational Health↗