Damaged goods: does disability disQALYfy people from just health care?
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Attitude of Health Personnel↗
Biomedical subjects
A Silvers
Publications and source records attributed to A Silvers.
Unit risk estimates for airborne arsenic exposure: an updated view based on recent data from two copper smelter cohorts.
The current unit risk for airborne arsenic, 4.29 x 10(-3), was established by the EPA in 1984. Using updated results from a cohort mortality study on Tacoma smelter workers and recent findings from a cohort study of 3619 Swedish smelter workers, new unit risk estimates were developed for the respective cohorts. Methods were analogous to those used by the EPA in 1984, and all estimates were derived under an absolute risk model. A new unit risk 1.28 x 10(-3), was estimated for the Tacoma smelter cohort which was a factor of 5 less than the EPA's earlier estimate, and a direct result of radically revised exposure estimates. A unit risk of 0.89 x 10(-3) was estimated from the Swedish study. Pooling these new unit risk estimates with the EPA's earlier estimates from the Montana smelter cohort yielded a composite unit risk of 1.43 x 10(-3). Based on this estimate, the present unit risk may overestimate the effects of airborne arsenic by a factor of 3. A need to update the unit risk for airborne arsenic and the collateral IRIS database is evident from the results.
Air Pollutants, Occupational↗
Plasma lipid effects of three common vegetable oils in reduced-fat diets of free-living adults.
We compared plasma lipid changes due to the polyunsaturated fatty acids (PUFAs) in partially hydrogenated soybean oil, corn oil, and sunflower oil fed in reduced-fat diets (22-26% of total energy). Each oil was the dominant fat in isoenergetic diets of centrally prepared foods consumed by 26 male and 35 female normolipidemic, free-living individuals. Test diets were consumed double-blind, alternating with self-selected diets for 5 wk each. The ranges of proportions of total fat were: 4.7-9.7% polyunsaturated fat, 8.9-14.2% monounsaturated fat and 5.4-7.4% saturated fat. All three diets lowered (P < 0.0001) total cholesterol (11%), LDL cholesterol (13%), and HDL cholesterol (10%), without triglyceride changes. We conclude that PUFAs at approximately 6% of total energy result in clinically relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat, reduced-saturated-fat diets.
Adult↗
How children spend their time: a sample survey for use in exposure and risk assessments.
Children are becoming an increasingly important focus for exposure and risk assessments because they are more sensitive than adults to environmental contaminants. A necessary step in measuring the extent of children's exposure and in calculating risk assessments is to document how and where children spend their time. This 1990-1991 survey of 1000 households was designed for this purpose, targeting children between 5 and 12 years of age, in six states in varied geographic regions. The behavior of children was sampled on both weekdays and weekends over all four seasons of the year using a retrospective time diary to allocate time to activities during the previous 24 h. Information was obtained on the kinds and locations of activities, the nature of the microenvironments of the locations, and the time spent in the different environments. Measures of variability in addition to mean hours per day are reported. Results of this study closely match those of earlier research on California children's activities done by the California Air Resources Board. One important finding of the survey was that 5- to 12-year-old children in all geographic regions spend most of their time indoors at home, indicating that risk assessments should focus on indoor, onsite hazards.
Child↗
Use of biological markers in risk assessment.
Measurements of intermediate end points in the carcinogenic process may reduce uncertainty in human risk assessment from bioassay data, by identifying sources of interspecies variation and dose nonlinearity. This paper describes desirable properties of such markers: persistence, predictive power, temporal relevance, and consistency across dose rate and species. We illustrate these properties by evaluating markers for squamous cell nasal carcinoma in rodents exposed to formaldehyde. We also discuss design issues for bioassays that evaluate markers and tumors simultaneously at necropsy.
Animals↗
Pharmacokinetics in low dose extrapolation using animal cancer data.
Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.
Animals↗
Chemical spill exposure assessment.
POSSM, the PCB On-Site Spill Model, is a contaminant transport model developed to predict environmental concentrations associated with a chemical spill. The model predicts daily changes in chemical concentrations on a spill site (e.g., in soil and on vegetation) and losses of chemical due to volatilization, surface runoff/soil erosion, and leaching to groundwater. Spill areas consisting of soil/vegetation and/or an impervious surface (e.g., asphalt and concrete) can be analyzed, as can different spill cleanup practices. POSSM is used to analyze exposure levels associated with a hypothetical capacitor spill. While the model was developed for PCB spills, it is generally applicable to a number of organic compounds.
Accidents↗
Plasma lipid and lipoprotein response of humans to beef fat, coconut oil and safflower oil.
This study's purpose was to evaluate the fasting human plasma lipid and lipoprotein responses to dietary beef fat (BF) by comparison with coconut oil (CO) and safflower oil (SO), fats customarily classified as saturated and polyunsaturated. Nineteen free-living normolipidemic men aged 25.6 +/- 3.5 yr consumed centrally-prepared lunches and dinners of common foods having 35% fat calories, 60% of which was the test fat. The test fats were isocalorically substituted, and each fed for five weeks in random sequences with intervening five weeks of habitual diets. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations among individuals follows the same relative rank regardless of diet. Triglycerides (TG) concentrations among individuals also maintain their relative rank regardless of diet but in a different order from that of the cholesterols. Plasma TC, HDL-C, and LDL-C responses to BF were significantly lower and TG higher than to CO. As compared to SO, BF produced equivalent levels of TG, HDL-C, and LDL-C and marginally higher TC. Thus, the customary consideration of BF as "saturated" and grouping it with CO appears unwarranted.
Adult↗
The statistical analysis of adherence data obtained from markers.
Adherence markers provide new kinds of clinical trial data. Adherence data on individual participants obtained from markers can be used for designing the trial sample size and stratification, evaluating the adequacy of randomization, directing the management of adherence, and analyzing and interpreting the trial's final results. Examples of these are presented. Analyses of adherence data can employ conventional procedures. Box plot techniques are proposed for flagging extreme values of the distribution of adherence either at a single time point or in a time continuum. The effect of difference in distribution of the markers in two or more groups in a clinical trial is discussed. Survival analysis is illustrated as one technique in univariate and multivariate analysis of markers with covariate effects. Design considerations with markers in a clinical trial are discussed, with particular emphasis on some of the assumptions and biases that must be considered for the analysis.
Clinical Trials as Topic↗
Clinical trials methods and the practice of medicine.
An important potential byproduct from clinical trials is validated clinical methods applicable to clinical practice. The potential for improved patient care is separate from the scientific and intellectual answers gained in such trials. The current mechanisms for the transfer of methodological information from clinical trials are inefficient and have identifiable barriers. Methods validated in clinical trials must be recognized and accentuated as a valuable resource. A central repository of clinical trials' methods and a retrieval system dedicated to this unique body of scientific literature is warranted. Reports of methodological advances from clinical trials should be published in the literature read by clinical practitioners. The effective transfer of methods information from clinical trials to the office of the clinical practitioner is possible but requires increased efforts on the part of clinical trials scientists.
Clinical Trials as Topic↗
Managing cardiac disease in patients with diabetes mellitus.
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Aged↗
The influence of residual disease after coronary bypass on the 5-year survival rate of 1274 men with coronary artery disease.
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Adult↗
Clinical results of coronary bypass in 500 patients at least 10 years after operation.
We determined the outcome of coronary artery bypass surgery in 500 consecutive patients followed for at least 10 years after operation. There were 446 males (89.2%). Angina pectoris was the major indication for operation. Four hundred six patients (81%) had multivessel coronary artery disease and 348 (69.9%) had good left ventricular function. At 10 years of follow-up, 48% of patients were asymptomatic and 41% were improved. Propranolol was being used by 36% of patients and nitrates by 49%. Of the 355 patients younger than 65 years of age at the time of follow-up, 57% were employed full time and 24% were working part-time. Reoperation was performed in 9% of patients. Analysis of survival by Kaplan-Meier curves indicated that overall 10-year survival rates were 78% for one-vessel disease, 69% for two-vessel disease, 48% for three-vessel disease and 67% for left main coronary artery disease. For patients with good left ventricular function, the 10-year survival rates were 83% for one-vessel disease, 73% for two-vessel disease, 53% for three-vessel disease and 73% for left main disease. For patients with poor left ventricular function, the rates were 56%, 59%, 40% and 54%, respectively. Cox multivariate analysis indicated that preoperative diuretic use, history of heart failure, the number of diseased vessels, and infarct on the preoperative ECG were all good predictors of survival. This study shows that the outcome of coronary artery bypass surgery 10 years operation is highly favorable.
Angina Pectoris↗
Infrarenal abdominal aortic aneurysm: factors influencing survival after operation performed over a 25-year period.
This report is concerned with the factors influencing survival in 920 consecutive patients submitted to operation for infrarenal abdominal aortic aneurysm during the past 25 years. Rupture had occurred in 60 patients (6.5%) and survival was 77%, which did not vary during the period of study. Of the 860 patients (93.5%) treated for nonrupture, 819 (95%) survived operation. The mortality rate in this group varied from 18%, in the earlier period to 1.43% , in recent years. Risk factors including heart disease, hypertension, and advanced age accounted for 95% of the deaths that occurred within 30 days however, the mortality rate in patients with these problems decreased from 19.2% to 1.9% during the period of study although the average number of patients treated each year with these risk factors increased tenfold. Improvements in operative techniques and experience were responsible for decreasing mortality up to about 1971. Subsequent decrease in mortality was due to improvements in anesthesia, monitoring, and other supportive measures during operation and the early recovery period. Complete survival information was obtained in 816 (99.6%) patients, 191 of whom had been treated for periods over 15 years. Factors influencing long-term survival were associated disease and age at time of operation. Survival in percentage in patients without associated heart disease of hypertension for 5, 10, and 15 years was 84, 49, and 21; with heart disease, it was 54, 34, and 17. The median age of patients in the series was 65.5 years and survival at above intervals according to quartile was less than or equal to 60; 71, 53, and 24; 60 less than age less than or equal to 71; 66, 38, and 18; less greater than 71; 43, 13, and 11.
Adolescent↗
Tumoricidal response induced by cytosine arabinoside after plasma perfusion over protein A.
In dogs with spontaneous mammary adenocarcinomas, a single nontoxic infusion of cytosine arabinoside after extracorporeal perfusion of plasms over immobilized protein A resulted in a necrotizing response rapid in onset and specific for tumorous tissue. Gross tumoricidal reactions 12 hours after this combined treatment exceeded the algebraic sum of responses to cytosine arabinoside and protein A perfusion treatments alone in the same dogs, implying a synergistic effect between the two. The magnitude, rapidity, and specificity of the tumoricidal response after the combined treatment suggests that it may be an effective chemimmunotherapeutic approach to breast adenocarcinoma.
Adenocarcinoma↗
Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release.
Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.
Actins↗
Late results of reconstructive surgery for renovascular disease.
In order to determine the late results of reconstructive surgery for renovascular disease, a review was made of a series of 505 consecutive patients who underwent operation over a 20-year period. There were 257 males (50.9%) with an age range of 3-80 years. Renal artery bypass grafts were used in 75.4% (471/625) and thromboendarterectomy and/or patch angioplasty in 15.0% (94/625) of reconstructions. Associated vascular procedures were performed in 38.0% (186/489) of patients. Operative mortality (30-day) was 1.8% (9/489) overall, and 4.8% (9/186) with associated procedures but there was no operative mortality in 303 consecutive isolated renal artery reconstructions. The blood pressure was normal or improved in 65% of patients at a mean follow-up interval of 49.3 months, range 1-240 months. The best response rate was obtained in younger patients with isolated renal lesions. Linear regression analysis showed age at operation to be the most important determinant of blood pressure response (p < 0.003) with the presence or absence of diffuse atherosclerosis as another but less powerful determinant of responsiveness (p < 0.07). Crude 15-year survival was 70% (340/489). The overall five- and ten-year actuarial survival probabilities were 80 and 62% respectively. The most common causes of death were myocardial infarction, stroke, and cancer. Cox regression analysis for variables influencing survival indicated that age at operation (p < 0.001), sex (p < 0.01) and the presence or absence of fibromuscular disease (p < 0.002) were the major determinants of late survival with persistent severe hypertension exerting an important but lesser influence. The results of this study indicate that about two-thirds of patients will experience long-term relief of hypertension after operation and that the best long-term survival and blood pressure relief will be obtained in patients less than 50 years of age. Because hypertension in females is better tolerated, younger, male patients appear to have the most to gain from successful renovascular reconstruction.
Adolescent↗
Hyaline membrane disease and intraventricular haemorrhage in small for gestational age infants.
19 small for gestational age (SGA) infants with gestational ages less than or equal to 32 weeks were matched with 19 appropriate for gestational age (AGA) preterm neonates with similar risk factors for intraventricular haemorrhage and hyaline membrane disease. Gestational age, 1- and 5-minute Apgar scores, type of delivery, survival rate, use of corticosteroids before delivery, sex, twinning, presence of premature rupture of membranes, and birth date were comparable in the two groups. Gestational age of both groups was 30 (+/- 1.8) weeks, and birthweights were 919 (+/- 202) g (SGA group) and 1268 (+/- 212) g (AGA group). The incidences of hyaline membrane disease and intraventricular haemorrhage were different: 74 and 42% respectively for AGA neonates, 5 and 11% respectively for SGA infants. We suggest that a stressful environment in utero may enhance maturation and prevent hyaline membrane disease and intraventricular haemorrhage.
Cerebral Hemorrhage↗