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Biomedical subjects

T J Peters

Publications and source records attributed to T J Peters.

At least 55 records · Page 3Linked to original sources
PubMed2002

Alcohol increases c-myc mRNA and protein in skeletal and cardiac muscle.

The pathogenic mechanisms responsible for alcohol-induced muscle disease are unknown, although it is possible that increased proto-oncogene expression may be the causative process. Therefore, we investigated the responses of skeletal muscle c-myc protein and mRNA to a standard acute ethanol dosage regimen (75 mmol/kg/body weight [BW]) for 2.5 to 24 hours. Comparative studies were made on the heart. Acute ethanol administration in vivo led to an increase in c-myc proto-oncogene mRNA in rat skeletal and cardiac muscle. The changes in c-myc mRNA were mirrored by increases in the c-myc protein as demonstrated by immunohistochemistry. The changes in the c-myc protein were localized to the myonuclei, with no corresponding changes seen in the interstitial cell nuclei. This is the first report of altered proto-oncogene expression in muscle in response to ethanol. Increased c-myc mRNA and protein may reflect adaptive changes, a stress response, or another uncharacterized cellular adaptation.

Animals↗
PubMed2002

Quality of life, sleep, mood and alcohol consumption: a complex interaction.

Socio-demographic information was collected from 52 (45 men, seven women) currently drinking moderately dependent alcohol misusers attending an outpatient clinic in South London for medical assessment and treatment. Assessments at baseline and 12-week follow-up included: (i) Severity of Alcohol Dependence (SADQ) (baseline only), (ii) Hospital Anxiety and Depression Scale (HADS); (iii) Nottingham Health Profile sleep subscale (NHP) and (iv) the EuroQoL (EQ-5D). The main outcome measure was drinking at a "sensible level" at 12-week follow-up as recommended by the Royal College of Psychiatrists. There were significant interactions between sleeping badly, lying awake at night and HADS depression scores. The Health-related Quality of Life (HrQoL) of this group was poor compared to general population norms. Lower EQ-5D index scores were associated with poorer educational attainment and lower EQ-5D Visual Analogue Scale (VAS) patient ratings with greater baseline alcohol consumption. Clinician ratings on the EQ-5D VAS were consistently lower than the patient ratings. The correlations between patient self-assessment and clinician ratings (EQ-5D VAS) were not significant. The forty-seven subjects (90%) who were successfully followed-up showed a significant reduction in the total amount of alcohol consumed. Ten (21%) subjects returned to sensible drinking levels at 12 weeks but there was not a corresponding improvement in HrQoL, sleep, or affective status scores or biochemical measures in these subjects.

Adult↗
PubMed2002

Chemical and analytical aspects of areca nut.

A capillary zone electrophoretic (CZE) method for the rapid analysis of the major alkaloids (arecoline and guavacoline) in areca nut extract is described. Areca nuts were pulverized and then extracted with water by sonication in a water bath. After centrifugation, the supernatant was analysed on a fused-silica capillary with 100 mM ammonium acetate-acetic acid (pH 4.6) as the running buffer at a voltage of 20 kV and temperature of 30 degrees C. The method is applicable to the analysis of alkaloids in the nut, commercial preparations (pan masala) and in the saliva of areca nut chewers.

Alkaloids↗
PubMed2002

Obesity as a cause of "false-positive" alcohol misuse laboratory investigations.

Three patients are reported with a prior history of alcohol misuse accompanied by abnormal liver toxicity tests and other indices of alcohol misuse. A decreased but persistently raised serum gamma-glutamyl transferase activity during subsequent abstinence or controlled drinking was interpreted incorrectly as due to continued alcohol misuse whereas obesity-related fatty liver was the probable cause. The value of serum carbohydrate deficient transferrin assays in the differential diagnosis of abnormal liver toxicity tests is emphasized.

Alcoholism↗
PubMed2002

An evaluation of the First Parent Health Visitor Scheme.

AIMS: To assess outcomes in families who received the First Parent Health Visitor Scheme (FPHVS), in comparison with families who received conventional ("generic") health visiting. METHODS: Retrospective data on 2113 families were collected during 1986-92 as part of National Health Service (NHS) service provision. Prospective data were collected during 1993-98 on 459 mothers and their children, with outcomes assessed at one year (93% follow up) and two years (80% follow up). RESULTS: There were no differences between the groups of mothers in self esteem, locus of control, or depression rates. The women who received the FPHVS were more likely to have changed partners, but they also had a wider support network than comparison women, and consulted their general practitioner (GP) less often. Breast feeding rates were higher in the FPHVS mothers, who also gave their infants more fruit juice drinks than the comparison group. No differences were apparent in developmental outcome using the Bayley Scales at 1 and 2 years of age. Both height and weight Z scores at 2 years of age were lower in the FPHVS children than the comparison children. Receipt of the FPHVS was associated with increased use of electric socket covers and lower accident rates in the second year of life. No differences were seen in immunisation rates, uptake of child health surveillance, or use of hospital services. A higher proportion of families who received the FPHVS were registered on the local child protection register compared with comparison families. CONCLUSION: Clustering effects dominated the analysis, but overall this evaluation could not show a clear advantage for the FPHVS over conventional health visiting.

Adolescent↗
PubMed2002

Tamoxifen-related porphyria cutanea tarda.

We report a case of porphyria cutanea tarda (PCT) in a patient with breast cancer following adjuvant tamoxifen. Cessation of tamoxifen resulted in a prompt decline in urinary porphyrins suggestive of a causative role. Tamoxifen is known to be hepatotoxic; however, its association with PCT is unclear. In this report, we discuss the porphyrinogenicity of tamoxifen and potential mechanisms.

Anticarcinogenic Agents↗
PubMed2001

Randomized trial evaluating the framing of cardiovascular risk and its impact on blood pressure control [ISRCTN87597585].

BACKGROUND: The format or frame in which the results of randomized trials are presented has been shown to influence health professional's self-reported practice. We sought to investigate the effect of framing cardiovascular risk as two different formats in a randomized trial. METHODS: We recruited 457 patients aged between 60 and 79 years with high blood pressure from 20 family practices in Avon, UK. Patients were randomized to cardiovascular risk presented either as 1) an absolute risk level (AR) or as 2) the number needed to treat to prevent an adverse event (NNT). The main outcome measures were: 1) percentage of patients in each group with a five-year cardiovascular risk > or = 10%, 2) systolic and diastolic blood pressure, 3) intensity of prescribing of cardiovascular medication. RESULTS: Presenting cardiovascular risk as either an AR or NNT had no impact reducing cardiovascular risk at 12 month follow up, adjusted odds ratio 1.53 (95%CI 0.76 to 3.08). There was no difference between the two groups in systolic (adjusted difference 0.97 mmHg, 95%CI -2.34 mmHg to 4.29 mmHg) or diastolic (adjusted difference 0.70 mmHg, 95%CI -1.05 mmHg to 2.45 mmHg) blood pressure. Intensity of prescribing of blood pressure lowering drugs was not significantly different between the two groups at six months follow up. CONCLUSIONS: Presenting cardiovascular risk in clinical practice guidelines as either an AR or NNT had a similar influence on patient outcome and prescribing intensity. There is no difference in patient outcomes when these alternative formats of risk are used in clinical practice guidelines.

Aged↗
PubMed2001

Alcoholic myopathy: biochemical mechanisms.

Between one- and two-thirds of all alcohol abusers have impairment of muscle function that may be accompanied by biochemical lesions and/or the presence of a defined myopathy characterised by selective atrophy of Type II fibres. Perturbations in protein metabolism are central to the effects on muscle and account for the reductions in muscle mass and fibre diameter. Ethanol abuse is also associated with abnormalities in carbohydrate (as well as lipid) metabolism in skeletal muscle. Ethanol-mediated insulin resistance is allied with the inhibitory effects of ethanol on insulin-stimulated carbohydrate metabolism. It acutely impairs insulin-stimulated glucose and lipid metabolism, although it is not known whether it has an analogous effect on insulin-stimulated protein synthesis. In alcoholic cirrhosis, insulin resistance occurs with respect to carbohydrate metabolism, although the actions of insulin to suppress protein degradation and stimulate amino acid uptake are unimpaired. In acute alcohol-dosing studies defective rates of protein synthesis occur, particularly in Type II fibre-predominant muscles. The relative amounts of mRNA-encoding contractile proteins do not appear to be adversely affected by chronic alcohol feeding, although subtle changes in muscle protein isoforms may occur. There are also rapid and sustained reductions in total (largely ribosomal) RNA in chronic studies. Loss of RNA appears to be related to increases in the activities of specific muscle RNases in these long-term studies. However, in acute dosing studies (less than 1 day), the reductions in muscle protein synthesis are not due to overt loss of total RNA. These data implicate a role for translational modifications in the initial stages of the myopathy, although changes in transcription and/or protein degradation may also be superimposed. These events have important implications for whole-body metabolism.

Alcoholism↗
PubMed2001

An iron-regulated ferric reductase associated with the absorption of dietary iron.

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.

Amino Acid Sequence↗
PubMed2001

Acute effect of ethanol on 7-hydroperoxycholesterol in muscle and liver.

We tested the hypotheses that ethanol sensitivities of muscle and liver can be discerned in the initial periods of ethanol exposure, especially when acetaldehyde levels are markedly raised with cyanamide, an aldehyde dehydrogenase inhibitor. To test this, we measured cholesterol hydroperoxides in soleus (Type I) and plantaris (Type II) muscle in four groups of rats acutely (i.e., 2.5 h) exposed to: [S] saline (control), [Cy] cyanamide, [EtOH] ethanol, or [Cy + EtOH] cyanamide + ethanol. Comparative reference was also made to the response of the liver. After 2.5 h, ethanol alone significantly increased 7 alpha-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH) and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH) levels in plantaris muscle. Identical qualitative effects were seen in rats treated with cyanamide + ethanol, but there was no discernible difference between groups [EtOH] and [Cy + EtOH]. In both the soleus muscle and liver, none of the treatments with either ethanol or cyanamide + ethanol had any effect on any of the measured parameters. This is the first report of a differential response of 7 alpha-OOH and 7 beta-OOH in Type II, compared to Type I predominant muscles, and the first time that muscle has been shown to be more sensitive than the liver in terms of its lipid marker response to oxidative stress. Perturbations in the muscle membrane lipid domain may contribute to impairment of muscle in alcoholism.

Acetaldehyde↗
PubMed2001

Self-rated psychosocial consequences and quality of life in the acute porphyrias.

A battery of self-report psychosocial measures was mailed to 116 patients who had been referred for clinical management (clinic attenders) or laboratory diagnosis (non-clinic attenders) to the London Supraregional Assay Service Centre for Porphyria over the past decade and who tested positive for porphyria. Usable replies were received from 81 (70%) patients. Our interest focused on the prevalence of psychosocial symptoms in acute porphyrias and the perceived effects of porphyria on quality of life and patient experience. Research questions examined included (i), lifestyle factors; (ii) life events; (iii) mental health; (iv) general health; and (v) perceptions of illness of patients receiving specialist clinical management compared to respondents referred for diagnostic investigations, between patients with latent or manifest symptomology and between patients with different types of porphyria. Patients with porphyria have an impaired quality of life, particularly manifest cases, compared to controls and to diabetic patients. Depression, and particularly anxiety, is more common than in the general population or general medical outpatient attenders. Quality oflife is lower in acute intermittent porphyria (AIP) than in other forms of porphyria and a significant number of patients had major life event consequences, e.g. failure to secure, or loss of, employment, limitation of family size. Patients attending a clinic providing specialist porphyria advice, management and counselling received some perceived lifestyle benefits.

Acute Disease↗
PubMed2001

Impaired prostate tumorigenesis in Egr1-deficient mice.

The transcription factor early growth response protein 1 (EGR1) is overexpressed in a majority of human prostate cancers and is implicated in the regulation of several genes important for prostate tumor progression. Here we have assessed the effect of Egr1 deficiency on tumor development in two transgenic mouse models of prostate cancer (CR2-T-Ag and TRAMP). Using a combination of high-resolution magnetic resonance imaging and histopathological and survival analyses, we show that tumor progression was significantly impaired in Egr1-/- mice. Tumor initiation and tumor growth rate were not affected by the lack of Egr1; however, Egr1 deficiency significantly delayed the progression from prostatic intra-epithelial neoplasia to invasive carcinoma. These results indicate a unique role for Egr1 in regulating the transition from localized, carcinoma in situ to invasive carcinoma.

Animals↗
PubMed2001

Vision-related quality of life impairment in an elderly UK population: associations with age, sex, social class and material deprivation.

PURPOSE: To describe the prevalence of vision-related quality of life (VR-QOL) impairment in an elderly UK population sample. METHOD: The survey, using the VCM1 questionnaire, was based on an age- and sex-stratified random population sample of 2783 individuals aged 55 years or over. RESULTS: One thousand eight hundred and forty-six (69.7%) of 2647 eligible subjects responded. One thousand six hundred and eighty-three individuals completed all 10 VCM1 items. Overall the prevalence of a VCM1 score >2.0 ('more than a little' concern about vision) was 4.6% (95% CI = 3.7% to 5.7%), leading to an estimate of more than 550,000 individuals in England with substantial VR-QOL impairment. The prevalence increased with age from 2.1% in the 55-64 year age group to 17.9% in the group aged 85 years and older. The prevalence also increased as social class became lower, from 0 in social class I to 10.2% in social class V, and increased with increasing material deprivation, from 1.2% in the most affluent quintile to 6.8% in the most deprived quintile. Multivariable logistic regression analysis showed that age (p = 0.0001), decreasing social class (p = 0.03) and increasing material deprivation (p = 0.008) were independently associated with VR-QOL impairment (VCM1 score >2.0), whilst gender and means of questionnaire administration were not associated with VR-QOL impairment at the 5% level. CONCLUSIONS: The findings suggest a substantial national prevalence of VR-QOL impairment, and are consistent with earlier studies linking ocular disease with social deprivation. Consideration should be given to directing resources more carefully towards groups at higher risk of VR-QOL impairment, in particular the very elderly and socially deprived.

Age Factors↗
PubMed2001

The population requirement for cataract extraction: a cross-sectional study.

PURPOSE: To examine the distribution in the population of indications for cataract extraction in order to relate demand for this procedure to the capacity for satisfying it. METHODS: An age-stratified random population sample of 2783 individuals aged 55 years and over was taken from inner-city, urban and rural areas of Avon and Somerset. The requirement for cataract extraction was estimated on the basis of measures of vision-related quality of life, refracted visual acuity, and application of the Oxford Clinical Cataract Classification and Grading System. Data were also collected concerning suitability for surgery, including relative contraindications to surgery and whether participants considered their eyesight bad enough to merit surgery. Three sets of composite indications were defined. RESULTS: Estimated prevalent requirements for cataract extraction for the three sets of composite criteria were: 29 per 1000 aged over 55 years (95% CI 20-41) for the most inclusive criterion; 17 per thousand (95% CI 10-27) for the intermediate criterion; and 7 per thousand (95% CI 3-14) for the most stringent criterion. These rates are equivalent to a national prevalent requirement for England of 384,000 for the most inclusive criterion. If the approximately 15% of individuals whose desire or fitness for surgery was questionable are removed from this estimate, the prevalent requirement, including the backlog from previous unsatisfied demand, becomes 325,000 individuals. CONCLUSIONS: The findings suggest only a modest imbalance between supply and demand for cataract surgery. In particular there was a very small prevalence of untreated severe cataract, less than the annual health service surgical capacity, suggesting that the current National Health Service surgical capacity is adequate for cases of severe cataract.

Age Distribution↗
PubMed2001

The Relationship between LUTS and sexual function.

Lower urinary tract symptoms (LUTS) are common in middle-aged and elderly men and are frequently caused by an enlarged prostate. Increasing severity of LUTS may negatively affect patients' health-related quality of life (QoL) to varying degrees. Sexual function is an important aspect of QoL and studies show that sexual dissatisfaction increases with increased severity of LUTS. The ICS-BPH International Study of 1271 men aged 45 y and over who reported to one of 12 clinics examined the relationship between urodynamic parameters, LUTS, sexual dysfunction and QoL. Results showed that nearly 90% of men found that the effect of LUTS on their sex lives was a problem and 45% reported that their sex lives were spoilt by LUTS. Storage symptoms, in particular incontinence, had a greater association with sexual dysfunction than voiding symptoms. Similar results were reported in the ICS-BPH UK Community Study, which involved 423 men aged 40 y and over. In contrast, a French Community Study of 2011 men aged 50-80 y reported that symptoms of hesitancy, straining, reduced stream and wet underclothes were most strongly associated with sexual dysfunction. Sexuality is clearly of concern to men with LUTS and should be included in discussions on treatment decisions.Prostate Cancer and Prostatic Diseases (2001) 4, S2-S6

Journal Article↗