Trends in acoustic neuroma and cellular phones: is there a link?
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Cell Phone↗
Biomedical subjects
P Elliott
Publications and source records attributed to P Elliott.
Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle.
PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.
Adult↗
No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort.
AIMS/HYPOTHESIS: Although the variable number tandem repeat (VNTR) minisatellite 5' to the insulin gene is among the most studied polymorphisms in diabetes, the relationships between VNTR variation, diabetes-related traits and predisposition to type 2 diabetes remain unclear. Since inadequate sample size is likely to have been an obstacle to reliable inference, we examined the relationship between VNTR variation and a range of diabetes-related traits in a cohort of 5,753 Finnish adults. MATERIALS AND METHODS: VNTR genotypes were derived, by typing at the -23HphI variant site, for 5,646 individuals from the Northern Finland Birth Cohort 1966. Associations were sought between these genotypes and a range of anthropometric (BMI, WHR), physiological (blood pressure) and biochemical (fasting glucose, insulin, lipids, indices of insulin sensitivity and beta cell function) measures obtained at clinical examination at 31 years. RESULTS: We found no evidence that VNTR genotype was significantly associated with measures of insulin secretion, insulin sensitivity, glycaemia, adiposity or blood pressure. CONCLUSIONS/INTERPRETATION: Despite evidence from several relatively small studies suggesting that INS-VNTR genotypes are associated with predisposition to type 2 diabetes, reduced beta cell function and measures of adiposity, the present study failed to detect any association with a range of diabetes-related traits. Taken with other recent studies in large population-based cohorts, these data suggest that previous studies have, at the very least, overestimated the influence of the INS-VNTR on type 2 diabetes-related traits. The effects of INS-VNTR variation on insulin transcription observed in vitro appear not to translate into detectable differences in basal insulin secretion in humans.
Adult↗
Linezolid-induced dyserythropoiesis: chloramphenicol toxicity revisited.
We report here two cases of dyserythropoietic anaemia associated with long-term linezolid use that share striking similarities to chloramphenicol-associated myelotoxicity.
Acetamides↗
Excess risk of kidney disease in a population living near industrial plants.
Runcorn has been a site of chemical industry activity for over a century, where tons of toxic chemicals are released annually to air and water. Excess kidney disease mortality (nephritis, nephrotic syndrome, and nephrosis) was found in the population living within 2 km of the industrial plants (standardised mortality ratio (SMR) in males 131 (95% CI 90 to 185) and females 161 (95% CI 118 to 214)) compared to a reference population (northwest England)). Risk of hospital admissions for kidney disease in Halton (comprising the towns of Runcorn and Widnes) was higher than in the less industrial, nearby town of Warrington. The standardised admission ratio (SAR) in Halton was 115 (95% CI 107 to 124) for males and 126 (95% CI 117 to 137) for females; and in Warrington 91 (95% CI 85 to 97) for males and 84 (95% CI 78 to 91) for females compared to the Warrington and Halton area as a whole. The excess risk of kidney disease in the Runcorn area requires further investigation.
Chemical Industry↗
Protease expression in the supernatant of Chinese hamster ovary cells grown in serum-free culture.
The protease activity secreted by the Chinese Hamster Ovary (CHO-K1) cell line grown in serum-free medium was examined by substrate gel electrophoresis (zymography). The cell line expressed extracellular proteases that were active on gelatin zymograms but not on casein zymograms. The main protease band visible by gelatin zymography was approx. 92 kDa. Incubation of the conditioned medium with aminophenylmercuric acetate (APMA) resulted in the appearance of gelatinase activity at 82 kDa. Incubation of the conditioned media with EDTA significantly decreased the gelatinolytic activity of both the 92 kDa and 82 kDa forms, indicating the gelatinase responsible was a metalloprotease. Immunoblotting of the conditioned medium showed the gelatinase to be the pro- form of matrix metalloprotease-9 (pro-MMP-9), also known as gelatinase B.
Animals↗
INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary).
Blood pressure (BP) above optimal (< or =120/< or =80 mmHg) is established as a major cardiovascular disease (CVD) risk factor. Prevalence of adverse BP is high in most adult populations; until recently research has been sparse on reasons for this. Since the 1980s, epidemiologic studies confirmed that salt, alcohol intake, and body mass relate directly to BP; dietary potassium, inversely. Several other nutrients also probably influence BP. The DASH feeding trials demonstrated that with the multiple modifications in the DASH combination diet, SBP/DBP (SBP: systolic blood pressure, DBP: diastolic blood pressure) was sizably reduced, independent of calorie balance, alcohol intake, and BP reduction with decreased dietary salt. A key challenge for research is to elucidate specific nutrients accounting for this effect. The general aim of the study was to clarify influences of multiple nutrients on SBP/DBP of individuals over and above effects of Na, K, alcohol, and body mass. Specific aims were, in a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from 17 diverse population samples in China, Japan, UK, and USA, test 10 prior hypotheses on relations of macronutrients to SBP/DBP and on role of dietary factors in inverse associations of education with BP; test four related subgroup hypotheses; explore associations with SBP/DBP of multiple other nutrients, urinary metabolites, and foods. For these purposes, for all 4680 participants, with standardized high-quality methods, assess individual intake of 76 nutrients from four 24-h dietary recalls/person; measure in two timed 24-h urine collections/person 24-h excretion of Na, K, Ca, Mg, creatinine, amino acids; microalbuminuria; multiple nutrients and metabolites by nuclear magnetic resonance and high-pressure liquid chromatography. Based on eight SBP/DBP measurements/person, and data on multiple possible confounders, utilize mainly multiple linear regression and quantile analyses to test prior hypotheses and explore relations of multiple dietary and urinary variables to SBP/DBP of individuals. The 4680 INTERMAP participants are equally divided across four age/gender strata: diverse in ethnicity, education, occupation, physical activity; use of cigarettes, alcohol; diagnosed high BP, CVD, diabetes; CVD family history; women vary in parity, use of contraceptive medication and hormone replacement therapy.
Blood Pressure↗
INTERMAP: the dietary data--process and quality control.
The aim of this report is to describe INTERMAP standardized procedures for assessing dietary intake of 4680 individuals from 17 population samples in China, Japan, UK and USA: Based on a common Protocol and Manuals of Operations, standardized collection by centrally trained certified staff of four 24 h dietary recalls, two timed 24-h urines, two 7-day histories of daily alcohol intake per participant; tape recording of all dietary interviews, and use of multiple methods for ongoing quality control of dietary data collection and processing (local, national, and international); one central laboratory for urine analyses; review, update, expansion of available databases for four countries to produce comparable data on 76 nutrients for all reported foods; use of these databases at international coordinating centres to compute nutrient composition. Chinese participants reported 2257 foods; Japanese, 2931; and UK, 3963. In US, use was made of 17,000 food items in the online automated Nutrition Data System. Average time/recall ranged from 22 min for China to 31 min for UK. Among indicators of dietary data quality, coding error rates (from recoding 10% random samples of recalls) were 2.3% for China, 1.4% for Japan, and UK; an analogous US procedure (re-entry of recalls into computer from tape recordings) also yielded low discrepancy rates. Average scores on assessment of taped dietary interviews were high, 40.4 (Japan) to 45.3 (China) (highest possible score: 48); correlations between urinary and dietary nutrient values--similar for men and women--were, for all 4680 participants, 0.51 for total protein, range across countries 0.40-0.52; 0.55 for potassium, range 0.30-0.58; 0.42 for sodium, range 0.33-0.46. The updated dietary databases are valuable international resources. Dietary quality control procedures yielded data generally indicative of high quality performance in the four countries. These procedures were time consuming. Ongoing recoding of random samples of recalls is deemed essential. Use of tape recorded dietary interviews contributed to quality control, despite feasibility problems, deemed remediable by protocol modification. For quality assessment, use of correlation data on dietary and urinary nutrient values yielded meaningful findings, including evidence of special difficulties in assessing sodium intake by dietary methods.
Adult↗
Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study.
The purpose of the study was to compare nutrient intakes among Chinese, Japanese, UK, and US INTERMAP samples, and assess possible relationships of dietary patterns to differential patterns of cardiovascular diseases between East Asian and Western countries. Based on a common Protocol and Manuals of Operations, high-quality dietary data were collected by four standardized 24-h dietary recalls and two 24-h urine collections from 17 population samples in China (three samples), Japan (four samples), UK (two samples), and USA (eight samples). There were about 260 men and women aged 40-59 years per sample--total N=4680. Quality of dietary interview and data entry were monitored and enhanced by extensive systematic ongoing quality control procedures at local, country, and international level. Four databases on nutrient composition of foods from the four countries were updated and enhanced (76 nutrients for all four countries) by the Nutrition Coordinating Center, University of Minnesota, in cooperation with Country Nutritionists. The mean body mass index was much higher for Western than East Asian samples. Macronutrient intakes differed markedly across these samples, with Western diet higher in total fat, saturated and trans fatty acids, and Keys dietary lipid score, lower in total carbohydrate and starch, higher in sugars. Based on extensive published data, it is a reasonable inference that this pattern relates to higher average levels of serum total cholesterol and higher mortality from coronary heart disease in Western than East Asian populations. The rural Chinese diet was lower in protein, especially animal protein, in calcium, phosphorus, selenium, and vitamin A. Dietary sodium was higher, potassium lower, hence Na/K ratio was higher in the Asian diet, especially for Chinese samples. This pattern is known to relate to risks of adverse blood pressure level and stroke. At the end of the 20th century, East Asian and Western diets remain significantly different in macro- and micronutrient composition. Both dietary patterns have aspects that can be regarded, respectively, as adverse and protective in relation to the major adult cardiovascular diseases. In both Asian and Western countries, public efforts should be targeted at overcoming adverse aspects and maintaining protective patterns for prevention and control of cardiovascular diseases.
Adult↗
Dietary intake in male and female smokers, ex-smokers, and never smokers: the INTERMAP study.
This report examines dietary intakes in smokers, ex-smokers, and never smokers in INTERMAP. The 4680 participants aged 40-59 years-from 17 population samples in four countries (China, Japan, UK, USA)-provided four 24-h recalls to assess nutrient intakes and two 24-h urine collections to assess excretion of urea, sodium (Na), potassium (K), etc. Compared to never smokers, current smokers generally consumed more energy from alcohol and saturated fats (SFA), less energy from vegetable protein and carbohydrates, less dietary fibre, vitamin E, beta carotene, vitamin C, thiamine, riboflavin, folate, vitamin B6, calcium, iron, phosphorus, magnesium (Mg), and K per 1000 kcal, excreted less K and urea (marker of dietary protein), had a lower ratio of polyunsaturated fat (PFA) to SFA intake, higher Keys dietary lipid score, and higher dietary and urinary Na/K. There were few differences between smokers and never smokers for total energy intake, energy from total and animal protein, monounsaturated fats, PFA, omega 3 and omega 6 PFA, dietary cholesterol, total vitamin A, retinol, vitamin D, vitamin B12, and urinary and dietary Na. Compared to ex-smokers, smokers generally consumed less energy from vegetable protein, omega 3 PFA, carbohydrates, less dietary fibre, beta carotene, vitamin E, vitamin C, thiamine, riboflavin, folate, vitamin B6, iron, phosphorus, Mg, had lower PFA/SFA, and excreted less urea and K. In conclusion, INTERMAP results are consistent with other reports indicating that smokers have less healthful diets than nonsmokers. Public health interventions in smokers should focus not only on helping them to quit smoking but also on improving their diets to further reduce cancer and cardiovascular disease risks.
Adult↗
Higher blood pressure in middle-aged American adults with less education-role of multiple dietary factors: the INTERMAP study.
Extensive evidence exists that an inverse relation between education and blood pressure prevails in many adult populations, but little research has been carried out on reasons for this finding. A prior goal of the INTERMAP Study was to investigate this phenomenon further, and to assess the role of dietary factors in accounting for it. Of the 4680 men and women aged 40-59 years, from 17 diverse population samples in Japan, People's Republic of China, UK, and USA, a strong significant inverse education-BP relation was manifest particularly for the 2195 USA participants, independent of ethnicity. With participants stratified by years of education, and assessment of 100+ dietary variables from four 24-h dietary recalls and two 24-h urine collections/person, graded relationships were found between education and intake of many macro- and micronutrients, electrolytes, fibre, and body mass index (BMI). In multiple linear regression analyses with systolic BP (SBP) and diastolic BP (DBP) of individuals the dependent variables (controlled for ethnicity, other possible nondietary confounders), BMI markedly reduced size of education-BP relations, more so for women than for men. Several nutrients considered singly further decreased size of this association by > or =10%: urinary 24-h Na and K excretion, Keys dietary lipid score, vegetable protein, fibre, vitamins C and B6, thiamin, riboflavin, folate, calcium, magnesium, and iron. Combinations of these dietary variables and BMI attenuated the education-SBP inverse coefficient by 54-58%, and the education-DBP inverse coefficient by 59-67%, with over half these effects attributable to specific nutrients (independent of BMI). As a result, the inverse education-BP coefficients ceased to be statistically significant. Multiple specific dietary factors together with body mass largely account for the more adverse BP levels of less educated than more educated Americans. Special efforts to improve eating patterns of less educated strata can contribute importantly to overcoming this and related health disparities in the population.
Adult↗
Tissue Doppler, strain, and strain rate echocardiography for the assessment of left and right systolic ventricular function.
Tissue Doppler (TDE), strain, and strain rate echocardiography are emerging real time ultrasound techniques that provide a measure of wall motion. They offer an objective means to quantify global and regional left and right ventricular function and to improve the accuracy and reproducibility of conventional echocardiography studies. Radial and longitudinal ventricular function can be assessed by the analysis of myocardial wall velocity and displacement indices, or by the analysis of wall deformation using the rate of deformation of a myocardial segment (strain rate) and its deformation over time (strain). A quick and easy assessment of left ventricular ejection fraction is obtained by mitral annular velocity measurement during a routine study, especially in patients with poor endocardial definition or abnormal septal motion. Strain rate and strain are less affected by passive myocardial motion and tend to be uniform throughout the left ventricle in normal subjects. This paper reviews the underlying principles of TDE, strain, and strain rate echocardiography and discusses currently available quantification tools and clinical applications.
Echocardiography, Doppler, Color↗
No excess risk of adverse birth outcomes in populations living near special waste landfill sites in Scotland.
A recent study showed small excess risks of low birth weight, very low birth weight and certain congenital anomalies in populations living near landfill sites in Great Britain. The objective of the current study was to investigate the risk of adverse birth outcomes associated with residence near special waste landfill sites in Scotland. We studied risks of adverse birth outcomes in populations living within 2 km of 61 Scottish special waste landfill sites operational at some time between 1982 and 1997 compared with those living further away. 324,167 live births, 1,849 stillbirths, and 11,138 congenital anomalies (including terminations) were included in the study. Relative risks were computed for all congenital anomalies combined, some specific anomalies and prevalence of stillbirth and low and very low birth weight (< 2500 g and < 1500 g). For all anomalies combined, relative risk of residence near special waste landfill sites was 0.96 (99% confidence interval 0.89 to 1.02) adjusted for confounders. Adjusted risks were 0.71 (0.36 to 1.42) for neural tube defects, 1.03 (0.85 to 1.26) for cardiovascular defects, 0.84 (0.58 to 1.22) for hypospadias and epispadias (with no excess of surgical corrections), 0.78 (0.27 to 2.23) for abdominal wall defects (1.32 (0.42-4.17) for hospital admissions), 1.22 (0.28 to 5.38) for surgical correction of gastroschisis and exomphalos and 1.01 (0.96 to 1.07) and 1.01 (0.90 to 1.15) for low and very low birth weight respectively. There was no excess risk of stillbirth. In conclusion, we found no statistically significant excess risks of congenital anomalies or low birth weight in populations living near special waste landfill sites in Scotland.
Adolescent↗
Recognising the psychosocial issues involved in hand hygiene.
Non-adherence to hand hygiene among those involved in the provision of health care is the principal route by which infection is spread. However, despite an extensive research base, regular education and the application of prescriptive rules there has been a consistent failure to achieve long-term adherence in appropriate hand hygiene practice. Where improved adherence has been achieved there has been little evidence to show that it was for anything other than a limited period with individuals ultimately reverting back to their original practice. This paper therefore proposes that the principal cause of non-adherence to safe hand hygiene practice among those involved in the provision of health care is psychosocial in its nature. Further, until strategies are developed that will reflect this, the well-being of individuals seeking health care intervention will continue to be compromised.
Attitude of Health Personnel↗
Cancer risks in populations living near landfill sites in Great Britain.
Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person-years for the adult cancer analyses and 113 631 443 person-years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.
Child↗
Self-reported problems: a comparison between PTSD-diagnosed veterans, their spouses, and clinicians.
This study investigated self-reported problems in a sample of help-seeking Vietnam veterans, comparing the veteran's own view with clinician and spouse perspectives, with the aim of examining convergence in reports across different informants. Veterans with PTSD (N = 459) were asked to list and rate their five most serious problems. Spouses and treating clinicians completed the same questionnaire in relation to the veteran. Rates of endorsement for each problem area, and levels of agreement between raters, were calculated. Veterans, spouses, and clinicians were all likely to rate anger as a high priority, with veterans also likely to nominate anxiety and depression. Spouses were likely to nominate more observable behavioural problems such as interpersonal difficulties and avoidance, while clinicians were likely to nominate indications of psychopathology, such as anxiety, depression, and intrusive thoughts. Agreement across raters was generally high, although interpretation of agreement levels was complex.
Anger↗
Current knowledge and recent developments in consumer exposure assessment of pesticides: a UK perspective.
Techniques employed in the assessment of consumer exposure to pesticides are currently being reviewed in the UK. This is not a formal process as is happening in the USA. However, the advent of probabilistic approaches and sophisticated computer models has prompted regulators, industry and other stakeholders in the UK to recognize the need for refinements in the risk-assessment process. Sources of information and data necessary to explore such refinements are disparate. This review aims to collate the information to present a coherent picture of the current knowledge, the data available and the stakeholders involved. It can then be used as a resource with which to investigate further more specific issues. Although focussing on the UK, the European context is included and reference is made to US models and developments that should be investigated. Factors hampering progress include the lack of sufficient data on which to base quantitative analysis, especially in the residential pesticides sector, and lack of experience in using and interpreting probabilistic models. At present, such techniques are being approached with some caution in the UK and in Europe, although their utility for cumulative assessment is accepted. Communicating results to both risk managers and consumers will be a considerable challenge.
Community Participation↗
Risk of adverse birth outcomes in populations living near landfill sites.
OBJECTIVE: To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. DESIGN: Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. SETTING: Great Britain. SUBJECTS: Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). MAIN OUTCOME MEASURES: All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). RESULTS: For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. CONCLUSIONS: We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities.
Congenital Abnormalities↗