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Biomedical subjects

T J Peters

Publications and source records attributed to T J Peters.

At least 37 records · Page 2Linked to original sources

Do height-related variations in insulin-like growth factors underlie the associations of stature with adult chronic disease?

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50-70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (P(trend) = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (P(trend) < 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

Aged↗

Are diet-prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-I and IGFBP-3 in healthy middle-aged men.

We examined the association of diet with insulin-like growth factors (IGF) in 344 disease-free men. Raised levels of IGF-I and/or its molar ratio with IGFBP-3 were associated with higher intakes of milk, dairy products, calcium, carbohydrate and polyunsaturated fat; lower levels with high vegetable consumption, particularly tomatoes. These patterns support the possibility that IGFs may mediate some diet-cancer associations.

Adult↗

Influence of specialization on the management and outcome of patients with pancreatic cancer.

BACKGROUND: Cancer care is increasingly specialized. Relationships between pancreatic cancer care, mortality and patterns of clinical practice among the full spectrum of patients, including those with irresectable tumours, are not well understood. METHODS: A cohort of 782 patients diagnosed prospectively with pancreatic cancer in 29 acute hospitals in England and Wales over 1 year were followed for 2-3 years. The effects of doctors' and hospitals' specialization, indicated by annual patient volumes, on operative mortality rates, survival times, and test and treatment provision were studied. Multiple logistic and Cox regression models were used to control for prognostic factors and treatments, providing adjusted odds and hazard ratios associated with a higher volume of ten patients annually. RESULTS: Patients managed by higher-volume hospitals survived significantly longer (hazard ratio 0.88 (95 per cent confidence interval (c.i.) 0.83 to 0.93); P < 0.001). They were more likely to undergo cytological examination (odds ratio (OR) 1.21 (95 per cent c.i. 1.01 to 1.35)), resection (OR 1.44 (1.17 to 1.79)) and biliary stenting (OR 1.17 (1.02 to 1.34)), and were less likely to have bypass surgery (OR 0.66 (0.55 to 0.78)). Patients of higher-volume doctors were more likely to undergo endoscopic retrograde cholangiopancreatography (OR 1.59 (1.19 to 2.11)), percutaneous transhepatic cholangiography (OR 1.50 (1.12 to 2.00)), laparoscopy (OR 1.81 (1.07 to 3.06)), resection (OR 1.84 (1.29 to 2.61)) and bypass surgery (1.71 (1.25 to 2.33)). CONCLUSION: Specialization appears to improve survival and to promote more thorough investigation.

Clinical Competence↗

Quality of life in alcohol misuse: comparison of men and women.

The theoretical and practical basis for Quality of Life assessment is briefly discussed. In the absence of a specific QoL measure for alcohol misusers, generic and symptom-specific measures have been used. Application of these instruments to alcohol misusers indicate severely impaired QoL, worse than that of patients with malignant disease. QoL improves with abstinence and deteriorates with relapse. Comparison of QoL in males and females indicates that for nearly all parameters, QoL in females is worse than in males, for comparable levels of dependency: Disturbed sleep with depression is a particular feature of the impaired QoL in female alcohol misusers. Comparison of the patients' perceptions of their QoL with that of their attending physician shows only a weak correlation between the two scores with that of the patients being consistently higher. Assessment of QoL in alcoholics is a valuable measure of clinical status and is more relevant than simple measures of alcohol consumption, or liver toxicity tests. It also helps to identify predictors of relapse and issues of major concern to the individual patient.

Alcoholism↗

International air travel: a risk factor for attacks in acute intermittent porphyria.

Five patients are reported with acute intermittent porphyria in whom attacks were apparently precipitated by international air travel. In four subjects this was the initial presenting attack and in a fifth the cause of an acute relapse in a patient requiring regular haem arginate prophylaxis. Multifactorial precipitants implicated include, dehydration, missed meals, alcohol use, infection, chronic hypoxia, premenstrual syndrome and stress. Acute intermittent porphyria should be suspected in individuals presenting with unexplained acute abdominal pain following international air travel. Appropriate precautions may reduce the incidence of attacks in known porphyrics.

Abdominal Pain↗

A 12-month follow-up of preschool children investigating the natural history of speech and language delay.

AIM: The aim of this paper is to examine the natural history of early speech and language delay in preschool children over a 12-month period. METHODS: The study reports data on 69 children under the age of 3.5 years who were referred for speech and language therapy because of early speech and language delay. The children were monitored over a 12-month period but received no direct intervention during that time. Assessment of their comprehension, expressive language and their phonology took place at baseline and again at 6 and 12 months after baseline. RESULTS: The results show a general picture of improvement, although there was considerable individual variation. By the end of the 12 months, two-thirds of the children were still eligible on the study intake criteria. Therapist's rating of a child's functional communication at the outset was a significant predictor of the child's outcome at the end of the 12-month period. DISCUSSION: The paper discusses the appropriateness of a 'monitoring' approach to the management of early language delay and highlights the need to consider the social issues and views of parents as well as the severity of a child's difficulties.

Articulation Disorders↗

Recent trends in the use of radical prostatectomy in England: the epidemiology of diffusion.

OBJECTIVE: To describe recent trends in the use of radical prostatectomy (RP) in England, as there is currently no consensus on the most effective treatment for localized prostate cancer, although RP is the treatment of choice among urological surgeons for men aged < 70 years. METHODS: Routine data were assessed to establish the number of RPs performed in England in 1991-99. Age-standardized operation rates were compared by region and socio-economic group, and the geographical spread of use mapped. RESULTS: The number of RPs performed annually increased nearly 20-fold between 1991 and 1999. Rates of surgery were greatest in the London National Health Service (NHS) regions and lowest in the Trent region. Outside London, the risk of surgery in a NHS hospital was significantly greater for men living in the least deprived areas; in London this trend was reversed. CONCLUSION: Rapid increases in the use of RP showed marked regional variations, most likely related to access to prostate-specific antigen testing and the location of surgeons able to carry out radical surgery. By 1999, a third of procedures were still being undertaken in 'low-volume' hospitals, with implications for the quality of care and outcomes. Crucially, these developments occurred in the absence of robust information about the effectiveness of RP. Recent funding of a randomized trial of treatment options in this area is welcome, but wider questions remain about the timing of the evaluation of surgical technologies.

Aged↗

The development and validation of a questionnaire to assess visual symptoms/dysfunction and impact on quality of life in cataract patients: the Visual Symptoms and Quality of life (VSQ) Questionnaire.

The aim of the study was to develop a new questionnaire to assess visual symptoms/dysfunction and impact on vision-specific quality of life for those undergoing second eye cataract extraction. Items for the VSQ questionnaire were devised with reference to existing literature and following consultation with eye care experts (n = 18) and interviews with cataract patients (n = 40). Piloting work conducted with 53 patients indicated that the questionnaire was promising, with a high level of internal consistency, low levels of missing data and indications that it was responsive to surgery. A modified version of the questionnaire was completed by 105 patients having received 'early' surgery and 103 scheduled for routine surgery within a randomised controlled trial evaluating the effectiveness of second eye cataract surgery. Analyses showed that the internal consistency of both the visual symptoms/dysfunction and quality of life areas was high (Cronbach's alpha 0.82 and 0.83, respectively). Highly significant improvements were found for early surgery patients (p < 0.0001), with little change among routine surgery patients. Two final versions of the VSQ questionnaire have been produced for future use in assessing visual symptoms/dysfunction and impact on vision-specific quality of life: a scoreable short form and more detailed and sensitive long form.

Adult↗

No change in apoptosis in skeletal muscle exposed acutely or chronically to alcohol.

The pathogenic mechanisms responsible for the deleterious changes in ethanol-exposed skeletal muscle are unknown, although apoptosis may be a causal process. We therefore investigated the responses of skeletal muscle to acute or chronic ethanol exposure in male Wistar rats. In acute studies, rats were dosed with ethanol (75 mmol (3.46 g)/kg BW) and killed after either 2.5 or 6 hours. In chronic studies, rats were fed ethanol as 35% of total dietary energy for 6 weeks. Apoptosis was determined by either DNA fragmentation or TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling) assays. The results showed that apoptosis was not increased in the ethanol-exposed muscle in both acute and chronic studies compared to appropriate controls.

Animals↗

Sequential studies of sleep disturbance and quality of life in abstaining alcoholics.

Previous studies in recently detoxified dependent alcoholics have shown severely disturbed sleep and impaired quality of life. Although this association has been found to predict short-term relapse to heavy drinking, no sequential studies have been conducted to monitor significant changes in sleep quality and quality of life in abstaining alcoholics. Fifty-seven inpatients at a voluntary sector 12-Step alcohol detoxification unit in South London were administered a series of questionnaires assessing sleep (Pittsburgh Sleep Quality Index, PSQI), Quality of Life (Euro-Qol) and Depression and Anxiety (Hospital Anxiety and Depression Scales, HADS). Questionnaires were administered at baseline and for 12 weeks at monthly intervals. At baseline, PSQI scores showed that 52 of the 57 participants suffered from impaired sleep. The scores, however, did not correlate significantly with any of the other measurements. All except two participants acknowledged impaired Quality of Life in at least one area. With respect to the follow-up measurements 23 (40%) participants completed the study. Quality of life and depression scores improved significantly over a 12-week period but sleep and anxiety scores did not. At 12 weeks the mean PSQI score was still above the cut-off point for 'sleep caseness'. Quality of life and depression show a significant improvement over a 3-month period of abstinence, although at this point the subjects are still experiencing difficulties with sleep and anxiety. This information could help in the planning of future rehabilitation and treatment programmes.

Adult↗

Comparison of methods for analysing cluster randomized trials: an example involving a factorial design.

BACKGROUND: Studies involving clustering effects are common, but there is little consistency in their analysis. Various analytical methods were compared for a factorial cluster randomized trial (CRT) of two primary care-based interventions designed to increase breast screening attendance. METHODS: Three cluster-level and five individual-level options were compared in respect of log odds ratios of attendance and their standard errors (SE), for the two intervention effects and their interaction. Cluster-level analyses comprised: (C1) unweighted regression of practice log odds; (C2) regression of log odds weighted by their inverse variance; (C3) random-effects meta-regression of log odds with practice as a random effect. Individual-level analyses comprised: (I1) standard logistic regression ignoring clustering; (I2) robust SE; (I3) generalized estimating equations; (I4) random-effects logistic regression; (I5) Bayesian random-effects logistic regression. Adjustments for stratification and baseline variables were investigated. RESULTS: As expected, method I1 was highly anti-conservative. The other, valid, methods exhibited considerable differences in parameter estimates and standard errors, even between the various random-effects methods based on the same statistical model. Method I4 was particularly sensitive to between-cluster variation and was computationally stable only after controlling for baseline uptake. CONCLUSIONS: Commonly used methods for the analysis of CRT can give divergent results. Simulation studies are needed to compare results from different methods in situations typical of cluster trials but when the true model parameters are known.

Breast Neoplasms↗

Inhibition of alcohol-associated colonic hyperregeneration by alpha-tocopherol in the rat.

BACKGROUND: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether alpha-tocopherol supplementation may prevent ethanol-induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis. METHODS: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol + alpha-tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) + alpha-tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti-proliferating cell nuclear antigen (PCNA) or anti-BCL2 antibodies. Fractional (k(s)) and absolute (V(s)) rates of protein synthesis and rates of protein synthesis relative to RNA (k(RNA)) and DNA (k(DNA)) were measured with a flooding dose of L-[4-3H] phenylalanine with complementary analysis of protein and nucleic acid composition. RESULTS: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 +/- 2.3 vs. control, 6.51 +/- 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor k(s), k(RNA), k(DNA), and V(s) were affected. This increase in PCNA index was significantly diminished by coadministration of alpha-tocopherol (ethanol + alpha tocopherol, 7.86 +/- 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 +/- 4.4 vs. control, 12.1 +/- 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor alpha tocopherol feeding had any significant effect on BCL-2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption. CONCLUSIONS: Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with alpha-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation.

Animals↗

Safety considerations for sample analysis using a near-infrared (785 nm) Raman laser source.

Raman spectroscopy is often considered a nondestructive analytical technique; however, this is not always the case. The 300-mW 785-nm near-infrared (NIR) laser source used with many commercially available instruments has sufficient power to burn samples. This destructive potential is of special concern if the sample is irreplaceable (e.g., fine art, forensic evidence, or for in vivo medical diagnostics) or a hazardous energetic material (explosive or pyrophoric samples). This study quantifies the heat resulting from illuminating an extensive color array with a 785-nm NIR laser and relates these values to the hazards associated with Raman analysis. In general, darker colors were found to be more problematic. Since visible colors are not ideally correlated with absorptive characteristics at 785 nm, predictions based on thermography are not perfect; however, this approximation gives a useful method for predicting the thermal response of unknown samples to NIR exposure. Additionally, experimental studies evaluated the analysis of flammable organic solvents, propellants, military explosives, mixtures containing military explosives, shock-sensitive explosives, and gunpowders (i.e., smokeless, black, and Pyrodex powders). Safety guidelines for analysis are presented.

Equipment Failure↗

The imPaCT study: a randomised controlled trial to evaluate a hospital palliative care team.

A randomised controlled trial was undertaken to assess the effectiveness of a hospital Palliative Care Team (PCT) on physical symptoms and health-related quality of life (HRQoL); patient, family carer and primary care professional reported satisfaction with care; and health service resource use. The full package of advice and support provided by a multidisciplinary specialist PCT ('full-PCT') was compared with limited telephone advice ('telephone-PCT', the control group) in the setting of a teaching hospital trust in the SW of England. The trial recruited 261 out of 684 new inpatient referrals; 175 were allocated to 'full-PCT', 86 to 'telephone-PCT' (2 : 1 randomisation); with 191 (73%) being assessed at 1 week. There were highly significant improvements in symptoms, HRQoL, mood and 'emotional bother' in 'full-PCT' at 1 week, maintained over the 4-week follow-up. A smaller effect was seen in 'telephone-PCT'; there were no significant differences between the groups. Satisfaction with care in both groups was high and there was no significant difference between them. These data reflect a high standard of care of patients dying of cancer and other chronic diseases in an acute hospital environment, but do not demonstrate a difference between the two models of service delivery of specialist palliative care.

Activities of Daily Living↗

Do patients who self-harm consult their general practitioner soon after hospital discharge? A cohort study.

BACKGROUND: Deliberate self-harm (DSH, attempted suicide) is one of the most common reasons for emergency hospital admission in Great Britain. Approximately 20 % of patients repeat self-harm in the 12 months after admission. The GP's role in DSH aftercare and the prevention of repeat episodes is unclear. METHODS: The data were obtained from a 12-month follow-up of a series of 968 consecutive patients from 49 practices who attended an accident and emergency (A&E) department in Bristol or Bath, UK, following an episode of self-harm between 26(th) May 1997 and 1(st) March 1999. RESULTS: Information on consultation patterns were available for 681 (70 %) of the patients. Two hundred and fourteen (31 %) of these consulted their GP in the week following the episode, 360 (53 %) within 4 weeks. Of the subjects, 44 % were discharged directly from A & E; these patients were more likely to consult their GP in the 4 weeks after the episode. Over the 12-month follow-up, 117 (17 %) attended hospital for a repeat episode of DSH; 9 % of these repeats occurred within 1 week and 28 % within 4 weeks of the index event. Although few (2 out of 11 patients--18 %) of those repeating in the first week after the index episode consulted their GP prior to repeating, 50 % (11/22) of those who repeated in the 1-4 weeks after an episode did so. CONCLUSIONS: Consultation patterns indicate that most people who deliberately self-harm consult their GP soon after the episode. This consultation may provide an opportunity for preventing repeat DSH and suicide.

Adolescent↗

Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers.

BACKGROUND: To evaluate specialization in National Health Service (NHS) cancer care, volume-outcome relationships were examined. METHODS: This was a cohort study of 1512 patients with oesophageal or gastric cancer in 23 acute NHS hospitals. Outcomes were survival time and operative (30 day) mortality. Multiple regression analysis was performed, adjusted for diagnoses, prognoses and treatments. RESULTS: For oesophageal cancer, the operative mortality rate decreased by 40 per cent (odds ratio 0.60 (95 per cent confidence interval (c.i.) 0.36 to 0.99 per cent); P = 0.047) for each increase of ten patients in doctors' annual surgical caseloads, and the risk of death decreased by 8 per cent (hazard ratio 0.92 (95 per cent c.i. 0.85 to 0.99); P = 0.021) for each increase of ten patients in doctors' annual caseloads. For gastric cancer, the operative mortality rate decreased by 41 per cent (odds ratio 0.59 (95 per cent c.i. 0.32 to 1.07)) for each increase of ten patients in doctors' annual surgical caseloads, and the risk of death decreased by 7 per cent (hazard ratio 0.93 (95 per cent c.i. 0.89 to 0.98); P = 0.009) for each increase of ten patients in hospitals' annual caseloads. Patients of higher-volume doctors were more likely to receive most investigations and treatments, independently of presenting features. CONCLUSION: The study supports concentration of services for oesophageal and gastric cancers. Specialization of doctors and their teams is at least as important as specialization of hospitals.

Cancer Care Facilities↗

Congenital erythropoietic porphyria: dilemmas in present day management.

Congenital erythropoietic porphyria is a rare autosomal recessive disorder of haem biosynthesis caused by a deficiency of uroporphyrinogen III synthetase. There is resultant accumulation and hyperexcretion of porphyrinogens of the isomer I variety. These are converted by spontaneous oxidation into their corresponding photoactive porphyrins leading to photodamage. Accumulation of porphyrins results in haemolysis and extensive photosensitivity. The consequences of chronic haemolysis are splenomegaly, reactive erythroid hyperplasia, erythrodontia, bone fragility, extreme photosensitivity and photomutilation. We present a 35-year-old man who has the severe infantile form and illustrates the haematological and photodestructive complications despite attempts at treatment with hypertransfusion, oral charcoal therapy and beta-carotene. Allogenic bone marrow transplantation has been considered but because of the high associated mortality this procedure has been discounted at present in the management of our patient.

Adult↗

Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo.

Alcohol can be considered as a nutritional toxin when ingested in excess amounts and leads to skeletal muscle myopathy. We hypothesized that altered protease activities contribute to this phenomenon, and that differential effects on protease activities may occur when: (1) rats at different stages in their development are administered alcohol in vivo; (2) acute ethanol treatment is superimposed on chronic alcohol-feeding in vivo; and (3) muscles are exposed to alcohol and acetaldehyde in vivo and in vitro. In acute studies, rats weighing approximately 0.1 kg (designated immature) or approximately 0.25 kg (designated mature) body weight (BW) were dosed acutely with alcohol (75 mmol/kg BW; intraperitoneal [IP], 2.5 hours prior to killing) or identically treated with 0.15 mol/L NaCl as controls. In chronic studies, rats (approximately 0.1 kg BW) were fed between 1 to 6 weeks, with 35% of dietary energy as ethanol, controls were identically treated with isocaloric glucose. Other studies included administration of cyanamide (aldehyde dehydrogenase inhibitor) in vivo or addition of alcohol and acetaldehyde to muscle preparations in vitro. At the end of the treatments, cytoplasmic (alanyl-, arginyl-, leucyl-, prolyl-, tripeptidyl-aminopeptidase and dipeptidyl aminopeptidase IV), lysosomal (cathepsins B, D, H, and L, dipeptidyl aminopeptidase I and II), proteasomal (chymotrypsin-, trypsin-like, and peptidylglutamyl peptide hydrolase activities) and Ca(2+)-activated (micro- and milli-calpain and calpastatin) activities were assayed. (1) Acute alcohol dosage in mature rats reduced the activities of alanyl-, arginyl- and leucyl aminopeptidase (cytoplasmic), dipeptidyl aminopeptidase II (lysosomal), and the chymotrypsin- and trypsin-like activities (proteosomal). No significant effects were observed in similarly treated immature rats. (2) Alcohol feeding in immature rats did not alter the activities of any of the enzymes assayed at 6 weeks. (3) In immature rats, activities of cathepsins B and D were not overtly affected at either 3, 7, 14, 28, or 42 days. (4) Superimposing acute (2.5 hours) on chronic (4 weeks feeding of immature rats) ethanol treatment (ie, chronic + acute) reduced the activities of cytoplasmic proline aminopeptidase and the chymotrypsin- and trypsin-like activities of the proteasome. (5) Cathepsin D activities were reduced in muscle homogenates upon addition of alcohol and acetaldehyde in vitro. (6) Cyanamide pretreatment in combination with alcohol dosage in immature rats did not significantly alter any protease activities. The data suggests that mature rats are more sensitive to the effects of acute alcohol on muscle proteases. Protease activities may be affected by acetaldehyde or alcohol levels as indicated by in vitro experiments. The reduction in muscle protease activities in chronic + acute alcohol superimposition may reflect the effect of acute alcohol dosage alone. Overall, there was no evidence for increased protease activity in any of the experimental situations.

Acetaldehyde↗