Neonatal screening for familial hypercholesterolaemia by immunoturbidimetric assay of apolipoprotein B in dried blood spots.
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Apolipoproteins B↗
Biomedical subjects
T J Peters
Publications and source records attributed to T J Peters.
Chronic effects of ethanol on muscle metabolism in the rat.
Chronic ethanol feeding in the rat is associated with a skeletal myopathy involving primarily type-II muscle fibres, which is recognised to be mediated via a specific impairment in protein turnover. This paper investigates whether the cause of this myopathy may be related to abnormalities in carbohydrate and lipid metabolism in different muscles. [U-14C]Glucose metabolism was examined in two muscles with different fibre compositions, the extensor digitorum longus (EDL) muscle, which contains predominantly type-II muscle fibres, and the soleus muscle, which is composed primarily of type-I muscle fibres. Feeding on the ethanol-supplemented Lieber-DeCarli liquid diet for 2 or 6 weeks was associated with profound disturbances in glucose metabolism in both EDL and soleus muscles, particularly in relation to rates of glycogen and alanine formation. We discuss the importance of these metabolic changes in relation to the genesis of chronic alcoholic skeletal myopathy.
Animals↗
Chemical and structural characterisation of iron cores of haemosiderins isolated from different sources.
The elemental content of the iron cores of haemosiderins isolated from animal and human tissues has been determined to ascertain whether changes in composition are correlated with structural differences previously identified in these mineralisation products. Significant differences were observed in the elemental composition of haemosiderins isolated from patients subjected to desferrioxamine-chelation therapy compared to patients who had been venesected. The P/Fe molar ratio was considerably higher in haemosiderin isolated from treated primary haemochromatosis (0.83), compared to untreated primary haemochromatosis (0.10) and treated secondary haemochromatosis (0.25), and this could account for the amorphous nature of these iron cores. The levels of M/Fe (M = Ca, Cu, Zn) were reduced in the haemosiderins derived from treated secondary haemochromatosis patients, possibly due to the chelation of these ions by desferrioxamine therapy. In an experimentally iron-loaded rat, receiving either desferrioxamine or 1,2-diethyl-3-hydroxypyrid-4-one, selective decreases in these three elements were also observed after two weeks of desferrioxamine therapy. Such changes may be important determinants in the modification of biomineralisation of the iron cores.
Animals↗
Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat.
The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.
Animals↗
King's model for allocating service increment for teaching and research (SIFTR).
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Costs and Cost Analysis↗
Investigation of a role for reduction in ferric iron uptake by mouse duodenum.
59Fe uptake rates by mouse duodenal fragments incubated in vitro were markedly reduced by non-permeable reagents, ferricyanide (oxidising agent) and ferrozine (Fe2+ chelator), in the medium; ferrocyanide had no effect. Reduction of Fe3+, as reflected by an increase in ferrozine-(Fe2+)-chelatable iron, was observed in the presence of the tissue fragments. The generation of Fe2+ occurred linearly with time, was independent of the medium ferrozine concentration, and was not due to release of reducing factors from the duodenal fragments. Fe(3+)-reducing activity was mainly present on the mucosal surface and was localised primarily to the proximal region of the small intestine. Changes in Fe3+ reduction rates closely parallelled the changes in duodenal 59Fe uptake, when metabolic inhibitors or modulators of membrane potential were included in the medium. The enhancement in duodenal mucosal 59Fe uptake in chronic hypoxic and iron-deficient mice parallelled the changes in the tissue reduction of medium Fe3+. Moreover, the rates of reduction were quantitatively similar to rates of uptake. These observations indicate that a sequential reduction and uptake process operates for Fe3+ uptake in mouse duodenum.
Animals↗
Alpha-tocopherol levels in brain are not altered in Parkinson's disease.
alpha-Tocopherol (vitamin E) levels in normal brain were lower in the cerebellum than in the cerebral cortex or basal ganglia. There was no difference in alpha-tocopherol levels in the cerebellum, basal ganglia, or cerebral cortex between control subjects and patients with Parkinson's disease.
Aged↗
Application of selective extraction to the study of iron species present in diet and rat gastrointestinal tract contents.
Iron speciation in rodent diet and rat gastrointestinal tract lumen during dietary digestion and absorption was investigated with a novel selective extraction technique. Five Fe fractions were identified, namely exchangeable (soluble in 1 M-magnesium chloride), carbonate-bound (soluble in mild acid), oxide-bound (soluble in hydroxylamine-acetic acid), organic-bound (soluble after treatment with peroxide in nitric acid) and residual. Fe from the pelleted diet was mobilized by rat stomach to the exchangeable fraction, then redistributed to the carbonate- and oxide-bound fractions on passage through the proximal small intestine. In vitro incubation of diet with hydrochloric acid failed to mimic the in vivo effect of the stomach. In vitro neutralization of stomach contents with bicarbonate was found to produce a similar effect on Fe speciation to that seen when diet passed the proximal small intestine in vivo. Comparison of 59Fe speciation in extrinsically labelled diet with endogenous Fe speciation showed that extrinsic labelling does not uniformly label all endogenous species. The experiments suggest that selective extraction may provide a useful approach to the study of Fe species present in diets, in vitro digestions and gastrointestinal contents.
Animals↗
Caring for elderly dependents: effects on the carers' quality of life.
This study describes a survey of 256 informal carers and elderly people they support, and examines the impact of the caring role upon quality of life. Carers reported that many aspects of their physical and mental health as well as their social and family lives were affected by their caring. For many the caring activity was unremitting. Overall, daughters were the most likely to report deleterious effects on their lives. Dominant factors associated with stress were the relationship between carer and dependent, sex of the carer and effects on social and family life. While relationship and sex were also associated with anxiety, loneliness was the dominant factor associated with anxiety and depression. Older age of the dependent was associated with stress, carer's disability was associated with anxiety, and depression in the elderly person was associated with depression in carers. These findings indicate that community services and future policies should be oriented towards the needs of carers and their families and not solely to the needs of frail elderly people. In particular there is a need to consider an increase in the provision of flexible planned respite care.
Activities of Daily Living↗
Pre- and perinatal factors and the risk of subsequent referral for hyperactivity.
Possible pre- and perinatal risk factors for subsequent referral for hyperactivity were assessed by comparing birth records of 129 referrals with the remaining 24,656 members of a geographically defined birth cohort. Relationships between the risk factors were accounted for using logistic regression methods. The significant factors were: social class, maternal age, antepartum haemorrhage, length of labour (second stage), 1-min Apgar and sex. Associations between referral for hyperactivity and the pregnancy, labour and birth outcome factors were not explained by the socio-demographic variables. The results suggest that such factors have a statistically significant association with referral for hyperactivity and may be of modest aetiological importance. However, the predictive power of the final set of factors remained low even on the original data set.
Apgar Score↗
Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration.
Much evidence suggests that recurrent oral aphthous ulceration (RAU) is an immunologically mediated disease. Tumour necrosis factor has multiple biologic properties, some of which may be relevant to the pathogenesis of RAU. This study has assessed its production by peripheral blood leukocytes from aphthous patients in active and remission phases of disease and from patients with nonaphthous ulceration (diseased controls). Each ulcer patient was studied in parallel with a matched healthy control volunteer. A bioassay against the standard mouse fibrosarcoma line, L929, was used to assess the levels of tumour necrosis factor-alpha (TNF). Significantly greater amounts of TNF were released from unstimulated monocyte-enriched and monocyte-depleted leukocyte fractions in active RAU compared with those from healthy control donors, suggesting that this cytokine may be associated with RAU.
Adolescent↗
Studies of gut mucosal protein synthesis in a non-steroidal anti-inflammatory drug (NSAID) model of inflammatory bowel disease.
The extent to which defects in protein synthesis occurred in an experimental indomethacin induced rat model of nonsteroidal enteropathy has been examined. Male rats (nine) were fed indomethacin (8 mg/kg/day) for three days mixed with a powdered form of chow. The control group of rats (nine) were fed the same diet for three days without indomethacin. After the feeding period, both groups were fed a normal solid diet for four days. At the end of this period, the fractional rates of intestinal protein synthesis was determined by the 'flooding dose' technique. The mucosal protein, RNA and DNA contents in the proximal ileum of animals with enteropathy were not significantly different from controls (p greater than 0.05). Experimental enteropathy induced selective increases in the fractional rates of protein synthesis (26% increase, p less than 0.03) and RNA activities (23% increase, p less than 0.04). There were no significant changes in any of these variables in the duodenum (p greater than 0.05 in all instances). These changes may partly reflect the activity of those processes responsible for the pathogenic changes in NSAID enteropathy.
Animals↗
Increased expression of c-myc proto-oncogene in biopsies of ulcerative colitis and Crohn's colitis.
The steady state levels of c-myc mRNA have been measured in RNA samples extracted from colonoscopic biopsies of inflammatory bowel disease patients obtained at routine endoscopy sessions. Biopsies were immediately frozen in liquid nitrogen limiting the ischaemic time to less than 15 seconds, and can be stored for up to 96 hours before separation of RNA. Yields of RNA using biopsies were 0.137 (0.041)% wet wt (mean (SD), n = 68), these are significantly better than those obtained from surgical material (0.064 (0.063)% wet wt (mean (SD), n = 21) where the tissue ischaemic time was 45 minutes to one hour 40 minutes. Functional activity of RNA extracted was demonstrated by the ability to direct in vitro protein translation in the rabbit reticulocyte system. We have used this technique to show that there is an increased ratio of steady state c-myc proto-oncogene expression in inflamed tissue from 18 patients with left sided ulcerative colitis and five patients with segmental Crohn's colitis, compared with an uninvolved region of the colon in each case. No difference in c-myc expression was seen in biopsies at least 30 cm apart in 11 control patients with no macroscopic or histological abnormalities. Increased expression of c-myc in inflammatory bowel disease is consistent with the activation of this proto-oncogene during altered cell cycle control resulting from the inflammatory process.
Adult↗
Auditing and improving notification and chemoprophylaxis in bacterial meningitis.
STUDY OBJECTIVE: The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. DESIGN: The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. SETTING: The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. POPULATION: Consisted of all the residents of Mid Glamorgan Health Authority. MAIN RESULTS: During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. CONCLUSIONS: As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine.
Communicable Disease Control↗
Mitochondrial gene expression in the human gastrointestinal tract.
In the human gastrointestinal epithelium, in situ hybridisation demonstrates that 12 S and 16 S mitochondrial ribosomal RNAs show maximal steady-state levels on the surface epithelial cells of the normal small intestine and colon. The mitochondrial mRNAs, cytochrome b and NADH dehydrogenase (IV) have a uniform distribution throughout the crypt and surface (villus) epithelial cells of the small intestine and colon. Histochemical stains for the activity of the mitochondrial respiratory chain enzymes succinate dehydrogenase and cytochrome oxidase also show almost uniform activities throughout the crypt-surface epithelial cell axis in the small and large intestines. In sections of normal human oesophagus the levels of mitochondrial ribosomal RNAs, mitochondrial mRNAs and the activities of mitochondrial respiratory chain enzymes are maximal over the basal cells of the stratified squamous epithelium. These results show a relative increase in mitochondrial ribosomal RNA expression compared with mitochondrial mRNAs in surface cells of simple intestinal epithelia.
DNA Probes↗
Immunity to self-antigens in periodontal disease.
Auto-antibody to collagen, previously detected in periodontal disease, may represent either a response to local tissue damage or be the manifestation of a disturbance of the host immune response induced by the periodontal flora and its products. In an effort to distinguish between these two hypotheses, this study was undertaken to determine circulating IgG auto-antibody levels in 41 periodontal-disease patients against 12 self-antigens (salmon DS-DNA, calf SS-DNA, human and bovine thyroglobulin, rabbit proteoglycan, horse myoglobin, bovine myosin, actin, fetuin, human transferrin, cytochrome C, and human Type I collagen) and compare them to those in 21 periodontal disease-free subjects. None of the detected IgG auto-antibody levels were significantly different between periodontal disease and control sera (Mann-Whitney U-test, P greater than 0.05) except for human Type I collagen (P less than 0.05). Fifty-six percent of patients and 38% of controls were "broad responders;" i.e., 50% or more of the auto-antibody levels were higher than the median values of the control group; however, these values were not significantly different using the chi-square test. It was concluded that the destruction of connective tissue components is the primary driving force in the induction of the enhanced auto-antibody response found in periodontal disease. This response is apparently secondary to the primary bacterial infection which remains the major etiologic event.
Adult↗
The antioxidant status of patients with either alcohol-induced liver damage or myopathy.
The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants alpha-tocopherol and beta-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of beta-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, beta-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas alpha-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both alpha-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers.
Adult↗
The acute effects of ethanol and acetaldehyde on rates of protein synthesis in type I and type II fibre-rich skeletal muscles of the rat.
Young rats were injected with either ethanol (75 mmol/kg), acetaldehyde (2.8 mmol/kg) or isovolumetric amounts of NaCl (0.15 mol/l, i.e. controls) with or without inhibitors of alcohol dehydrogenase (4-methylpyrazole) or aldehyde dehydrogenase (cyanamide). After 2.5 hr, fractional rates of protein synthesis (i.e. ks) in the soleus (Type I fibre-rich) and plantaris (Type II fibre-rich) muscles were measured. Ethanol alone reduced ks in both soleus and plantaris muscles, by approx. 25%. Pretreatment of ethanol-dosed rats with 4-methylpyrazole raised plasma ethanol levels and reduced ks in the soleus and plantaris by approx. 35%. Pretreatment of ethanol-dosed rats with cyanamide also increased plasma ethanol and further potentiated the effects of ethanol by reducing ks in the soleus and plantaris by approx. 65%. Acetaldehyde alone reduced ks by approx. 15%, and this effect was not significantly altered by 4-methylpyrazole pretreatment. In some instances, the plantaris was slightly more sensitive to ethanol and acetaldehyde than the soleus. Similar conclusions were derived when data were expressed relative to either RNA or DNA. The data thus suggest that the ethanol-induced inhibition of skeletal muscle protein synthesis may possibly be independently mediated by both ethanol and acetaldehyde.
Acetaldehyde↗