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Biomedical subjects

T J Peters

Publications and source records attributed to T J Peters.

At least 199 records · Page 11Linked to original sources

Ethanol acutely impairs glycogen repletion in skeletal muscle following high intensity short duration exercise in the rat.

Ethanol is recognized to affect adversely carbohydrate metabolism in skeletal muscle. This paper seeks to establish whether ethanol acutely impairs glycogen repletion during recovery from high intensity short duration exercise in the rat. High intensity exercise caused the massive mobilization of glycogen stores in muscles rich in type IIa and IIb fibres and marked increases in plasma and muscle lactate levels. During the 30-minute recovery period, there was substantial glycogen repletion in these muscles in both the ethanol-treated and control rats. Ethanol, however, was associated with reduced glycogen resynthesis in both the tibialis anterior (by 22%) and red gastrocnemius (by 31%) muscles but not in the white gastrocnemius muscle. This reduction in post-exercise glycogen deposition was accompanied by decreased lactate disposal and elevated plasma glucose levels. These effects of ethanol on glycogen repletion may involve interactions with hepatic gluconeogenesis, glucose uptake and utilization in muscle, muscle glycogen synthesis and lactate glyconeogenesis. The ethanol-mediated impairment in post-exercise glycogen repletion may have important implications for the pathogenesis of chronic alcoholic skeletal myopathy.

Journal Article↗

Factors associated with inappropriate emergency hospital admission in the UK.

This paper reports an attempt to assess the factors associated with inappropriate acute hospital admission using the technique of logistic regression. Data were obtained from two separate studies of acute hospital utilization in south-west England, conducted between 1992 and 1994. The appropriateness of admission was assessed using explicit standardized criteria in the form of the intensity-severity-discharge review system with adult criteria (ISD-A). Up to 19 explanatory variables were available for the analyses. These variables were modelled for each centre separately, using logistic regression to produce final sets of factors independently related to the appropriateness of admission. For one centre, the final model contained age/ specialty and use of community services. For the other, the final model contained two measures of health status on admission-coping failure and admission with stroke. It is concluded that the complex interplay between the characteristics of patients, referrers, alternative forms of care and the acute hospital may result in quite different types of inappropriate admissions in different locations.

Adolescent↗

A duodenal mucosal abnormality in the reduction of Fe(III) in patients with genetic haemochromatosis.

BACKGROUND: Previous in vitro studies have shown that the uptake of Fe(III) by freshly isolated duodenal mucosal biopsy specimens is increased in patients with genetic haemochromatosis. Moreover, in the mouse it has recently been found that reduction of Fe(III) to Fe(II) is a prerequisite for iron uptake by the proximal intestine. AIMS/METHODS: This study used the in vitro technique to investigate the rates of reduction and uptake of 59Fe(III) by duodenal mucosal biopsy specimens obtained at endoscopy from treated and untreated patients with genetic haemochromatosis. RESULTS: The rate of reduction of iron in the medium was proportional to the incubation time and was not caused by the release of reducing factors from the tissue fragments. Ferrozine, a specific Fe(II) chelator and ferricyanide, a non-permeable oxidising agent, inhibited uptake of 59Fe showing that reduction of Fe(III) precedes uptake. The rates (all values given as pmol/mg/min) of reduction (152 (49) v 92 (23)) and uptake (8.3 (4.0) v 3.6 (1.3), mean (SD)), were significantly increased in biopsy specimens from the untreated group (n = 6) compared with those from 10 control subjects (p < 0.04). Furthermore, the reduction and uptake rates were still increased in five patients in whom iron stores were normal after venesection treatment. CONCLUSIONS: These results show that there is a persistent abnormality in the reduction and uptake of iron by the intestine in genetic haemochromatosis.

Analysis of Variance↗

Epidemiology and patterns of hospital use after parasuicide in the south west of England.

OBJECTIVE: To describe the epidemiology, management, and outcome of parasuicide in the south west of England. DESIGN: Descriptive analysis using routine information systems. SETTING: The former South Western Regional Health Authority, population aged 10 and over: 2.9 million. SUBJECTS: These comprised 5080 residents of the South Western Health Region, admitted on 5770 occasions for parasuicide between April 1992 and March 1993 to hospitals in the south west. MAIN OUTCOME MEASURES: Person based age and sex standardised admission ratios for parasuicide; readmission for parasuicide in the subsequent 12 months; admission to psychiatric hospital after parasuicide; in-hospital mortality for those admitted after attempted suicide. RESULTS: The overall rate of parasuicide admission was 174 per 100,000 per year. Rates were highest in males aged 20-24 (381 per 100,000) and in females aged 15-19 (625 per 100,000). Parasuicide is the third most frequent cause of acute medical admission in the south west. A total of 10.0% of admissions received psychiatric inpatient care as a direct result of their parasuicide admission and 10.1% were readmitted in the following 12 months with a repeat episode of parasuicide. Significant variations in standardised admission ratios for parasuicide were observed between the districts. Some of this variation is related to socioeconomic differences between districts, the rest is probably due to differences in practice between districts. There is no clear evidence that these variations result in differences in readmission rates. Districts where psychiatric inpatient facilities were located on the same site as the general hospital tended to admit a greater percentage of parasuicide patients for psychiatric inpatient care. A quarter of all suicide deaths from overdose occurred in hospital. It is estimated that there are 87,000 parasuicide admissions in England and Wales annually. CONCLUSIONS: Parasuicide is a common cause of acute hospital admission and there is evidence that hospital admission practices for parasuicide vary across the south west. Randomised controlled trials are needed to evaluate the most appropriate form of management for those patients who do not require admission on medical grounds.

Adolescent↗

Breast screening: a randomised controlled trial in UK general practice of three interventions designed to increase uptake.

STUDY OBJECTIVES: To determine the relative effectiveness of three interventions designed to increase the uptake of breast screening. DESIGN: Randomised controlled trial of a nurse visit with health education (group A), nurse visit without health education (group B), and GP letter (group C). SETTING: The area of south east London served by the Butterfly Walk Breast Screening Unit in Camberwell. PARTICIPANTS: Women aged between 50 and 64 years who were registered with 27 GPs in the Lambeth, Southwark and Lewisham family health services authority and who had not attended for first round screening. MAIN RESULTS: Altogether 799 women were randomly allocated to the three groups. In general, delivering the nurse based interventions proved difficult. In group A, 11.4% (95% CI 7.9, 14.9%) of women subsequently attended for screening compared with 7.8% (95% CI 5.1, 11.4%) in group B and 13.1% (95% CI 7.9, 18.4%) in group C. The differences between the groups (95% CIs) were not statistically significant: A versus C, -1.7% (-8.0, +4.6%); B versus C, -5.3% (-11.3, +0.7%); A versus B, +3.6% (-1.0, +8.2%). CONCLUSIONS: A personal letter from the GP seems to be at least as effective at increasing the uptake of breast screening in non-attenders as a nurse making a home visit to discuss the issue of breast screening, and is not noticeably less effective than a visit at which a health education intervention is delivered. It is possible that the GP letter is considerably more effective than either of the two interview-based interventions. With regard to implementing strategies which will increase breast screening uptake and are cost effective, further trials of similar minimal interventions in primary care are required.

Breast Neoplasms↗

Expression of genes involved in iron metabolism in mouse intestine.

Intestinal nonheme iron levels and mRNA levels of genes implicated in iron metabolism were measured in mice with altered iron metabolism [chronic (4 wk) and acute (4 days) dietary iron deficiency; iron overload and hypoxia] to investigate their role in the process and regulation of intestinal iron absorption. Mucosal nonheme iron levels were decreased by both chronic and acute iron deficiency and increased by iron overload but were not affected by hypoxia. There was evidence of a gradient of mucosal nonheme iron along the small intestine (duodenum, jejunum > ileum). There were also regional differences in H-ferritin (duodenum > ileum) and transferrin receptor (ileum > duodenum) mRNA levels. Iron overload produced a decrease in transferrin receptor (TfR) mRNA in the duodenum, with ferritin mRNA levels unaffected in both the duodenum and ileum. Chronic iron deficiency induced a twofold increase in TfR mRNA levels in both the duodenum and ileum, whereas H- and L-ferritin mRNA levels did not change significantly. The ratio of H- to L-ferritin mRNA decreased significantly during exposure to hypoxia; however, individual ferritin and TfR mRNA levels were not significantly altered. Calreticulin (mobilferrin), cysteine-rich intestinal protein, and H(+)-adenosinetriphosphatase mRNA levels were virtually unchanged in all models. A comparison with previously published data on changes in iron absorption leads us to conclude that 1) iron absorption can be altered independently of effects on transcripts of genes for iron-related proteins, and 2) it is not essential for iron absorption to be coordinated with regulation of mucosal iron metabolism.

Animals↗

Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke. An enzymatic test for predicting outcome?

BACKGROUND AND PURPOSE: Few admission variables adequately predict neuronal damage and prognosis in individual patients after stroke. Therefore, there is a need for a reliable non-invasive surrogate measure of clinical outcome. METHODS: We have developed a surrogate measure of stroke outcome using the ratio of serum neuron-specific enolase (NSE) to human serum carnosinase (HSC) in 124 patients with acute ischemic or hemorrhagic stroke and 61 matched control subjects. Serum NSE is known to rise and HSC to fall after neuronal injury such as cerebral ischemia. RESULTS: Serum NSE levels were significantly higher and HSC levels lower in the patient group. The NSE/HSC ratio was elevated in patients with stroke: median (semiquartile) hemorrhages, 0.072 (0.033); infarcts, 0.039 (0.026); and control subjects, 0.019 (0.014), P = .0001. Patients with a primary intracerebral hemorrhage had nonsignificantly higher ratios than those with an infarct (P = .082). The NSE/HSC ratio was significantly associated with 90-day outcome measured in two out of three disability and handicap scales: modified Barthel Index (rs = -.34, P = .001), modified Rankin Scale (rs = .30, P = .002), and Lindley Score (rs = .19, P = .057). Patients who died or were institutionalized had higher ratios than those who were discharged home: 0.069 (0.043) versus 0.038 (0.024), P = .011. Correlations between the NSE/HSC ratio and outcome were comparable to those between patient age or consciousness level on admission and clinical outcome. CONCLUSIONS: We believe that measurement of NSE, HSC, or their ratio may be useful in the assessment of patients with acute stroke with respect to diagnosis and prediction of clinical outcome.

Acute Disease↗

The effect of eccentric exercise on serum creatine kinase activity in different ethnic groups.

Eccentric exercise causes release of muscle creatine kinase (CK) 3-4 days after exercise. Racial variation in basal serum CK has been reported but the reasons for this are unknown. We studied 30 subjects of different ethnic origin (Caucasian, Afro-Caribbean, Asian) before and after eccentric exercise. Basal serum CK was significantly higher in the Afro-Caribbean group (201 +/- 134 IU/L, median +/- SD) compared to Caucasians (81 +/- 57 IU/L). The Asian group had intermediate CK values (144 +/- 93 IU/L). The intra-individual range of peak post-exercise CK values obtained was very wide (95-30 200 IU/L) with little difference in median CK between the Afro-Caribbean (8450 +/- 9020 IU/L) and Caucasian groups (7600 +/- 8800 IU/L). The median value for the Asian group was lower (594 +/- 5410 IU/L). A sub-group of 15 individuals undertook a second bout of exercise 2 weeks later and all subjects demonstrated a training effect resulting in a marked attenuation of enzyme efflux. The variation in CK between the ethnic groups was not related to measurements of muscle strength or body mass, although the torque: body mass ratio followed the same order as the basal CK, i.e. the Afro-Caribbeans had the highest values. These results highlight the importance of considering ethnic origin and previous exercise history when interpreting serum CK assay results.

Adult↗

Determination of prostatic volume with transrectal ultrasound: A study of intra-observer and interobserver variation.

PURPOSE: We assessed the intra-observer and interobserver variation in measurements of prostatic volume using transrectal ultrasound. MATERIALS AND METHODS: Two volume estimations were performed by 1 observer in 40 patients and by 2 observers in 75. RESULTS: Mean prostatic volumes measured ranged from 18.9 to 87.0 ml. (median 39.8) for 1 observer and from 15.5 to 95.4 ml. (median 42.4) for 2 observers. The mean difference plus or minus standard deviation and limits of agreement between the paired volume estimations were 0.1 +/- 3.3 ml. and -6.5 +/- 6.7 ml., respectively, for 1 observer, and -0.3 +/- 5.3 ml and -10.9 to 10.3 ml., respectively, for 2 observers. The mean difference was 9.8% for 2 observers. The mean difference was 9.8% for 2 observers compared to 4.6% for 1. CONCLUSIONS: The results show that there is considerable variation in repeated measurements of prostatic volume and the variation is greatest for 2 observers compared to 1 observer.

Adult↗

A general practice-based study examining the absolute risk of cardiovascular disease in treated hypertensive patients.

BACKGROUND: When managing hypertension, the assessment of the absolute risk of a cardiovascular' event is now advocated as the most accurate way in which the risks and benefits of anti-hypertensive therapy should be judged. Most studies that have examined control of hypertension have relied solely on the blood pressure level attained after treatment, with no measurement of the likely absolute risk in individual patients. AIM: To assess control of hypertension by quantifying the 10-year absolute risk of cardiovascular disease in patients treated by their general practitioners, and to assess which risk factors are associated with uncontrolled hypertension in this group of patients. METHOD: A cross-sectional study was made of patients on drug treatment for hypertension in 18 Oxfordshire general practices subscribing to the VAMP (value-added medical products) computer system. The absolute risk of suffering a cardiovascular event in the following 10 years was measured according to each individual's risk factor profile. Factors associated with uncontrolled hypertension were ascertained using multiple logistic regression analysis. RESULTS: Overall, 40.9% (37.6% to 44.1%) of the hypertensive population had an absolute risk exceeding 20% of having a cardiovascular event in the following 10 years. The distribution of risk factors varies throughout the population. A higher blood pressure reading was strongly associated with an increased likelihood of high absolute risk, but high blood pressure readings in individual patients did not necessarily equate to a high absolute risk. The factors independently associated with uncontrolled hypertension were age, sex, past history of stroke, ischaemic heart disease and transient ischaemic attack, a body mass index greater than 30, diabetes, and current smoking. CONCLUSIONS: Absolute risk assessment maximizes the risk-benefit ratio in treated hypertensive patients. Individual control and management requires multifactorial assessment and management. Treatment of hypertension according to blood pressure reading alone is not a reliable way of reducing the absolute risk of cardiovascular disease.

Adult↗

Oral health in alcohol misusers.

One hundred and seven chronic alcohol misusers (mean age 42.9 years; range 21-65 years; 80 males) attending four centres in South East London were interviewed on their current and past alcohol consumption. Their nutritional status (body mass index (BMI) and mid arm muscle circumference) was also recorded. Each subject completed a dental and oral mucosal examination. Ninety four per cent of the sample consumed greater than 50 units of alcohol per week and 80 per cent greater than 100 units of alcohol per week. Smoking and alcohol misuse were found to be related, 81 per cent reporting both habits. Neither plaque index scores or mean subject pocket depths were correlated with alcohol consumption but both were positively correlated with the frequency and duration of smoking. Overall mean DMFT was 15.4; age specific mean DMFT and tooth loss of the sample were closely similar to the 1988 United Kingdom adult dental health survey data. The prevalence and severity of tooth wear and attrition were greater in the sample than levels described in the literature and these dental features may prove useful markers to the practitioner. Trauma to teeth and oral mucosae was noted in 25 per cent of the sample. Seven oral mucosal lesions (including one treated carcinoma) were detected; mucosal trauma could have acted as a co-factor. Furthermore, 21 per cent of the alcoholics were malnourished (BMI < 20). It is concluded that, unlike several reports from the United States, dental health in this sample of alcoholics is not compromised; however mucosal health is a cause for concern.

Adult↗

Relationship between duodenal cytosolic aconitase activity and iron status in the mouse.

Cytosolic aconitase activity was assayed in duodenal mucosa from mice subjected to a variety of manipulations known to modulate duodenal iron status and duodenal iron absorption. No changes in cytosolic aconitase activity were observed 1 h after oral FeSO4 dosing or intramuscular desferrioxamine treatment. Three days of hypoxic exposure and two weeks treatment with intramuscular iron dextran also had no effect on cytosolic aconitase. Three weeks growth on an iron deficient diet significantly reduced cytosolic aconitase activity. In no situation was there any evidence for significant amounts of inactive aconitase which could be activated in vitro with FeSO4/cysteine. These data suggest that duodenal cytosolic aconitase is not sensitive to acute changes in mucosal iron levels and is generally much less sensitive to body iron status than is duodenal iron absorption. There is evidence that chronic iron depletion reduces cytosolic aconitase to a relatively small degree but generally activity is maintained, consistent with an important metabolic role for the enzyme.

Aconitate Hydratase↗

Evidence based purchasing: understanding results of clinical trials and systematic reviews.

OBJECTIVE: To assess whether the way in which the results of a randomised controlled trial and a systematic review are presented influences health policy decisions. DESIGN: A postal questionnaire to all members of a health authority within one regional health authority. SETTING: Anglia and Oxford regional health authorities. SUBJECTS: 182 executive and non-executive members of 13 health authorities, family health services authorities, or health commissions. MAIN OUTCOME MEASURES: The average score from all health authority members in terms of their willingness to fund a mammography programme or cardiac rehabilitation programme according to four different ways of presenting the same results of research evidence--namely, as a relative risk reduction, absolute risk reduction, proportion of event free patients, or as the number of patients needed to be treated to prevent an adverse event. RESULTS: The willingness to fund either programme was significantly influenced by the way in which data were presented. Results of both programmes when expressed as relative risk reductions produced significantly higher scores when compared with other methods (P < 0.05). The difference was more extreme for mammography, for which the outcome condition is rarer. CONCLUSIONS: The method of reporting trial results has a considerable influence on the health policy decisions made by health authority members.

Decision Making↗

Relationship between early liver graft viability and enzyme activities in effluent preservation solution.

Determination of cellular enzyme activities in washout preservation solution used in hypothermic liver graft storage may allow development of an index that could be clinically valuable in prediction of early post-transplant graft function. In the present study, we collected washed out preservation fluid at the time of graft rinsing from 53 liver recipients. Aspartate aminotransferase and, to a lesser extent, lactate dehydrogenase levels correlated with early postoperative graft viability as assessed by 1-month graft survival and standard biochemical indices of liver function. Those patients with the highest aspartate aminotransferase activity in the washout preservation solution experienced the highest levels of this enzyme postoperatively (area-under-the-curve day 1-3; 1340 vs. 788 IU/L), total bilirubin (area-under-the-curve day 1-5; 901 vs. 538 mumol/L), and rejection frequency (67% vs. 31%) (all P < 0.05), with a significantly lower 1-month graft survival rate compared with patients with low effluent levels (62% vs. 92%, P < 0.05). Two markers of endothelial cell damage, purine nucleoside phosphorylase and a creatine kinase isoenzyme, measured in the fluid did not correlate with early graft viability. It is suggested that assay of aspartate aminotransferase activities in preservation fluid washout samples is a clinically useful indicator of graft viability.

Adult↗

Relation between parasuicide, suicide, psychiatric admissions, and socioeconomic deprivation.

OBJECTIVE: To examine the relations between parasuicide, suicide, psychiatric inpatient admissions, and socioeconomic deprivation. DESIGN: Ecological analysis with data from routine information systems and the 1991 census. SETTING: 24 localities in the area covered by the Bristol and District Health Authority (population 817,000), consisting of aggregations of neighbouring wards, with an average population of 34,000. SUBJECTS: 6089 subjects aged over 10 years admitted to hospital after parasuicide between April 1990 and March 1994; 997 suicides occurring 1982-91; 4763 subjects aged 10-64 years admitted with acute psychiatric illness between April 1990 and March 1994. RESULTS: Localities varied significantly in standardised admission ratios for parasuicide and standardised mortality ratios for suicide (P < 0.001). Spearman's rank correlation coefficient between the standardised mortality ratio for suicide and standardised admission ratio for parasuicide was 0.73 (95% confidence interval 0.46 to 0.88). Correlation between parasuicide and Townsend score was 0.86 (0.70 to 0.94) and between suicide and Townsend score 0.73 (0.46 to 0.88). The partial correlation coefficient between suicide and parasuicide after the Townsend score was adjusted for was 0.29 (-0.13 to 0.62). The correlation between standardised admission ratio for parasuicide and standardised admission ratio for psychiatric illness was 0.76 (0.51 to 0.89) and between standardised mortality ratio for suicide and standardised admission ratio for psychiatric illness was 0.72 (0.45 to 0.87). CONCLUSION: A strong ecological association exists between suicide and parasuicide, with socioeconomic deprivation accounting for much of this relation. This strong association provides supporting evidence for the importance of social policy measures in attaining Health of the Nation targets on mental health.

Adolescent↗

The influence of brain acetaldehyde on oxidative status, dopamine metabolism and visual discrimination task.

The toxic effect of acetaldehyde on brain oxidative capacity and dopamine metabolism has been investigated in rat brains after a single intraperitoneal injection of acetaldehyde (5 mmol/kg) and the results compared with those from chronically ethanol fed rats. Acetaldehyde was present in rat brain 120 hr after a single dose of acetaldehyde, confirming that it is able to cross the blood-brain barrier. Brain catalase increased significantly after acetaldehyde or chronic ethanol administration although there were no other significant changes in the total brain activity of superoxide dismutase, glutathione peroxidase or glutathione reductase. Dopamine turnover was increased in both experimental groups. The acute dose of acetaldehyde reduced the ability of the rats to relearn a computer visual discrimination task.

Acetaldehyde↗

Mitochondrial gene expression in small intestinal epithelial cells.

Most mitochondrial genes are transcribed as a single large transcript from the heavy strand of mitochondrial DNA, and are subsequently processed into the proximal mitochondrial (mt) 12 S and 16 S rRNAs, and the more distal tRNAs and mRNAs. We have shown that in intestinal epithelial biopsies the steady-state levels of mt 12 S and 16 S rRNA are an order of magnitude greater than those of mt mRNAs. Fractionation of rat small intestinal epithelial cells on the basis of their maturity has shown that the greatest ratios of 12 S mt rRNA/cytochrome b mt mRNA or 12 S mt rRNA/cytochrome oxidase I mt mRNA are found in the surface mature enterocytes, with a progressive decrease towards the crypt immature enteroblasts. Cytochrome b and cytochrome oxidase I mt mRNA levels are relatively uniform along the crypt-villus axis, but fractionation experiments showed increased levels in the crypt base. The levels of human mitochondrial transcription factor A are also greater in immature crypt enteroblasts compared with mature villus enterocytes. These results show that the relative levels of mt rRNA and mRNA are distinctly regulated in intestinal epithelial cells according to the crypt-villus position and differentiation status of the cells, and that there are higher mt mRNA and mt TFA levels in the crypts, consistent with increased transcriptional activity during mitochondrial biogenesis in the immature enteroblasts.

Adult↗

The hypotransferrinaemic mouse: ultrastructural and laser microprobe analysis observations.

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2- and 12-month-old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month-old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providing in situ documentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.

Animals↗