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Biomedical subjects

D A Evans

Publications and source records attributed to D A Evans.

At least 19 recordsLinked to original sources

Childhood blood pressure tracking correlations corrected for within-person variability.

The correlation coefficient between initial and subsequent blood pressure (BP) measurements is referred to as the tracking correlation. Childhood BP tracking correlations, although positive, have been considered too low to make accurate predictions for an individual. These correlations, however, can be raised substantially by averaging BP over multiple weekly visits in each year, which partially accounts for within-person variability. In a cohort of 333 school children, we measured BP 3 times on each of 4 successive weekly visits, in each of 4 consecutive years, using a random-zero sphygmomanometer. Approximately 90 per cent of subjects had data for one or more follow-up years, and 75 per cent of subjects who entered in the first year had data for all four years. With a model that allows estimation of correlations and that uses all available longitudinal data, we calculated tracking correlations completely corrected for within-person variability, the statistical equivalent of measuring BP on an infinite number (infinity) of visits and measurements per visit. Age-sex adjusted tracking correlations for 3 years of follow-up based on the means from 1,2,3,4, and infinity visits are, for systolic BP, 0.43, 0.56, 0.62, 0.66, and 0.73, respectively, and for diastolic BP, 0.20, 0.37, 0.46, 0.50, and 0.70, respectively. With longer follow-up, the use of corrected tracking correlations would allow determination of the maximal extent to which childhood BP can predict adult levels, and therefore the usefulness of screening to identify children at high risk of developing hypertension.

Adolescent

Relation of smoking and alcohol consumption to incident Alzheimer's disease.

The authors examined the effects of smoking and alcohol use in a prospective community-based study of incident Alzheimer's disease. Two in-home interviews of the total elderly population of East Boston, Massachusetts, conducted in 1982 and 1985 were used to sample individuals for clinical evaluation for Alzheimer's disease. A total of 513 persons underwent detailed clinical evaluation including neurologic, neuropsychologic, and psychiatric evaluation to diagnose Alzheimer's disease. In weighted logistic regression controlled for age, sex, and education, the estimated odds ratio of Alzheimer's disease was 0.7 (95% confidence interval 0.3-1.4) for ever smokers compared with never smokers. For 40 pack-years of smoking, the odds ratio of Alzheimer's disease was 0.8 (95% confidence interval 0.6-1.1). Consumption of 1 oz (30 ml) of alcohol per day was associated with an odds ratio of 1.1 (95% confidence interval 0.8-1.5). These results suggest that recent mild-to-moderate consumption of alcohol is not substantially related to incidence of Alzheimer's disease and that smoking does not increase risk of the disease.

Aged

Risk factors for delirium in hospitalized elderly.

OBJECTIVE: To determine risk factors for delirium in elderly hospitalized patients. DESIGN: Cohort analytic study. Using a reliable and valid instrument for detection of delirium, we prospectively followed up a cohort of elderly patients admitted to an acute care hospital. Using standardized criteria, we collected risk factor data from patient medical records. SETTING: General medical and surgical wards of a tertiary-care hospital. PATIENTS: Patients (n = 325) were 65 years of age or older, from either a geographically defined community or a long-term-care institution. We studied those patients (n = 291) not delirious on first evaluation. Fifty-seven patients or their families refused participation. MAIN OUTCOME MEASURES: Incidence of delirium and risk factors calculated as adjusted odds ratios (ORs). MAIN RESULTS: Delirium developed in 91 patients. By stepwise logistic regression, the independent risk factors for in-hospital delirium included prior cognitive impairment (OR, 8.97; 95% confidence interval [CI], 3.99 to 20.14), age over 80 years (OR, 5.22; 95% CI, 2.60 to 10.46), fracture on admission (OR, 6.57; 95% CI, 2.23 to 19.33), symptomatic infection (OR, 2.96; 95% CI, 1.42 to 6.15), and male sex (OR, 2.40; 95% CI, 1.19 to 4.84). Among medication groups, only neuroleptic use (OR, 4.48; 95% CI, 1.82 to 10.45) and narcotic use (OR, 2.54; 95% CI, 1.24 to 5.18) were independently associated with delirium. Anticholinergic use was not associated with delirium. CONCLUSIONS: Delirium in hospitalized patients is most closely associated with factors already present on admission such as prior cognitive impairment, advanced age, and fracture. In the hospital, use of neuroleptics and narcotics and the presence of infection are less strongly associated with this syndrome.

Age Factors

Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients.

We evaluated the occurrence and persistence of delirium in 325 elderly patients admitted to a teaching hospital from either a defined community or a long-term care facility. Of the study participants, 34 (10.5%) had Diagnostic and Statistical Manual of Mental Disorders, Third Edition--defined delirium at initial evaluation; of the remaining patients, 91 (31.3%) developed new-onset delirium. An additional 110 patients also experienced individual symptoms of delirium without meeting full criteria. Preexisting cognitive impairment and advanced age were associated with increased risk of incident delirium in the community sample but not the institutional one. Delirium was not associated with an increased risk of mortality, but it was associated with a prolonged hospital stay and an increased risk of institutional placement among community-dwelling elderly. Only five patients (4%) experienced resolution of all new symptoms of delirium before hospital discharge, and only 20.8% and 17.7%, respectively, had resolution of all new symptoms by 3 and 6 months after hospital discharge. These data suggest that delirium is a common disorder that may be substantially less transient than currently believed and that incomplete manifestations of the syndrome may be frequent.

Aged

Alzheimer's disease.

Alzheimer's disease is one of the most severe and most common chronic diseases of older persons. Because occurrence of the disease is strongly related to age, its public health impact is likely to continue to increase as the population ages. As with many other diseases, a diagnosis of Alzheimer's disease is made through a combination of clinical history, physical, and neurologic examination, and laboratory evaluation. Because the dominant feature of this disease is its effect on cognition, its diagnosis requires careful evaluation of cognitive function usually with formal neuropsychological performance testing. Clinical evaluation of persons for Alzheimer's disease has four objectives: (1) to determine as accurately as possible if the person has dementia; (2) if dementia is present, to determine whether its presentation and course are consistent with a diagnosis of Alzheimer's disease; (3) to assess evidence for any alternate diagnoses, especially if the presentation and course are atypical for Alzheimer's disease; and (4) to evaluate evidence of other, coexisting, diseases that may contribute to the dementia, with strong emphasis on conditions that might respond to treatment. There is no reliable antemortem diagnostic test for Alzheimer's disease; the main purpose of laboratory testing is to identify other conditions that might cause or exacerbate dementia. Pathologically, Alzheimer's disease is characterized by the presence of two lesions on microscopic examination of the brain: neuritic plaques and neurofibrillary tangles. Both lesions can be seen in the brains of older persons without dementia. However, they are found in greater numbers in the neocortex and hippocampus with Alzheimer's disease. Caring for patients with Alzheimer's disease is demanding and requires compassion and skills that go beyond the choices among sophisticated and effective therapies that characterize much of modern medical practice. The current lack of effective pharmacotherapy for cognitive dysfunction in Alzheimer's disease should not obscure that there are many areas in which intervention can improve quality of life for both the patient and the caregiver. Achieving success in these areas typically requires that the physician work effectively with providers of many other medical and nonmedical services. Community resources, advocacy, behavior management, and experimental therapies and procedures, should be discussed with the family of each patient. In addition, persons with mild disease should be promptly informed of their diagnosis in order to obtain their wishes regarding life prolonging measures and extended care options.

Aging

Murine teratology and pharmacokinetics of the enantiomers of sodium 2-ethylhexanoate.

A mouse model for the induction of exencephaly with sodium (+/-)-2-ethylhexanoate has been developed using multiple administration regimes. With three consecutive administrations at one-half-day intervals, the most sensitive time to induce exencephaly was Gestational Days 8-9. Using the racemic substance it was determined that the SWV strain was more sensitive to the induction of exencephaly than the C57BL/6NCrlBR strain. The enantiomers of 2-ethylhexanoic acid were separated via preparative HPLC to greater than 99.8% optical purity, and greater than 99% purity according to a gas chromatographic analysis. It was demonstrated that the (R)-enantiomer is a more potent teratogen than the (S)-enantiomer for the induction of exencephaly as well as malformations of other organ systems. Pharmacokinetic analyses for each of the enantiomers were performed in maternal plasma, maternal muscle, and embryo. The pharmacokinetics showed that the peak concentration (Cmax) for both enantiomers in the three compartments was approximately equivalent and was attained within 15 min following the third administration. The area under the concentration versus time curve values for the two enantiomers were approximately 10% higher for the (R)-antipode because of a slightly slower elimination of this compound. There was negligible (or no) racemization of the two enantiomers in the biological samples. The results suggest that teratologic differences in the enantiomers of sodium 2-ethylhexanoate are not due to differences in the concentrations of these antipodes in the embryo, but more likely result from the specific interaction of the enantiomers with chiral molecules in the embryo.

Abnormalities, Drug-Induced

Population prevalence estimates from complex samples.

Epidemiologic studies are often designed to severe several purposes. The complex sampling plans necessary to ensure an adequate number of cases, a similar age distribution among cases and controls, or other important design constraints for comparative studies may make the additional goal of estimating prevalence in the population or in important subgroups difficult to attain with existing computer software, which typically assumes simple random sample selection. We consider here various methods for estimating overall and subgroup prevalence from complex samples, including crude prevalences, direct standardization of prevalences, and standardization using logistic regression to smooth the sampling group prevalences. We illustrate these methods using a complex sample to estimate the prevalence of Alzheimer's disease in an urban community. A simulation study under various models in this setting is also described. We conclude that the use of logistic regression to smooth sampling group prevalences before standardization is an effective method for estimation of overall prevalence, provided that the adequacy of fit of a logistic model is carefully checked.

Aged

Assessing the validity of childhood blood pressure screening: unbiased estimates of sensitivity, specificity, and predictive values.

Blood pressure measurement in childhood can be considered as a screening test for future blood pressure levels. Evaluating this test involves calculating sensitivities, specificities, and predictive values for a blood pressure measurement at an initial time for predicting underlying true blood pressure at a subsequent time. We demonstrate the use of childhood blood pressure tracking correlations that are corrected for within-person variability to calculate unbiased estimates of these test characteristics. In a cohort of 333 schoolchildren, we measured blood pressure on multiple visits in each of 4 successive years. Using these data for within-person variances and corrected tracking correlations, and U.S. population data for means and total variances, we tabulated positive predictive values, sensitivities, and specificities for the case of predicting a 9-year-old male's true systolic blood pressure 3 years later. For example, if a 9-year-old's average blood pressure from 4 visits is 115 mmHg, the probability of his true blood pressure being greater than 116 mmHg (90th percentile) at age 12 is 0.50. With longer follow-up, the use of predictive values, sensitivities, and specificities that incorporate corrected correlations should allow determination of the accuracy of predicting adult blood pressure from childhood values, and therefore the usefulness of screening children for those at high risk of developing hypertension.

Adolescent

Gastrografin-induced aspiration pneumonia: a lethal complication of computed tomography.

A 43-year-old man with dysphagia and a tendency to aspirate was found to have squamous cell carcinoma of the esophagus. Curative surgery was planned and preoperative computed tomography of the chest and abdomen was ordered. A ward nurse administered Gastrografin according to a "standing" order, 4 hours before the CT was to be done. The patient aspirated about 50 mL of Gastrografin, and went into cardiorespiratory arrest caused by pulmonary edema. He sustained severe brain damage and died. This is a first report of lethal aspiration of Gastrografin, given in preparation for CT. We advise alerting nurses who administer Gastrografin, especially to patients with dysphagia or impaired consciousness about the grave consequences that can result if the contrast agent is aspirated by the patient. We further advise that responsibility for using contrast agents in radiologic procedures be assumed by the radiologist and not by medical house staff.

Adult

Light to moderate alcohol consumption and mortality in the elderly.

OBJECTIVE: To determine whether there is a relationship of low to moderate alcohol consumption with cardiovascular mortality in the elderly. DESIGN: Prospective cohort studies with 5-year mortality follow-up. SETTING: Three populations of community-dwelling elders. PARTICIPANTS: Population-based cohorts of men and women, aged 65 or older, in three populations. Subjects with prior myocardial infarction, stroke, or cancer, as well as those lacking alcohol consumption data, were excluded from statistical analyses leaving 2,694 subjects in East Boston, Massachusetts, 2,293 subjects in Iowa, and 1,904 subjects in New Haven, Connecticut. MAIN OUTCOME MEASUREMENTS: Alcohol consumption, total mortality, cardiovascular mortality, and cancer mortality. RESULTS: Low to moderate alcohol consumption was associated with statistically significant lowered total as well as cardiovascular mortality in East Boston and New Haven. The relative risks of total mortality for low to moderate consumers of alcohol compared to those consuming no alcohol in the previous year were 0.7 (95% CI 0.6-0.8) in East Boston and 0.6 (95% CI 0.5-0.8) in New Haven. For cardiovascular mortality, the RRs were 0.6 in East Boston and 0.5 in New Haven (95% CI's exclude null). These results persisted after control for potential confounding variables. In Iowa, there were no significant differences in total or cardiovascular mortality according to alcohol consumption patterns. For cancer mortality, there were no significant associations with alcohol consumption in any of the three populations. CONCLUSIONS: These data suggest that the relationship of low to moderate alcohol consumption with reduced total and cardiovascular mortality, which are well documented in middle age, also occur in older populations.

Activities of Daily Living

Effect of quassin on the metabolism of catecholamines in different life cycle stages of Culex quinquefasciatus.

Quassin, a mosquito larvicide isolated from Quassia amara, inhibits tyrosinase activity in the larvae of Culex quinquefasciatus. Since tyrosinase is directly involved in sclerotisation of the cuticle, it is suggested that quassin, as a larvicide, inhibits development of the cuticle. In presence of quassin phenylalanine, tyrosine and L-dopa levels were increased in larvae. In the larval stages, mosquitoes have a high concentration of phenylalanine and tyrosine with the level of the latter being very high just before pupation and then declines sharply. Monoamine oxidase (MAO), an enzyme directly involved in the metabolism of catecholamines, remained unaffected by quassin, in fact the level of adrenaline also remained unchanged in larvae during quassin poisoning. MAO showed high variation in its activity between synthetic and natural substrates. Tyramine is not a substrate for MAO. Tyrosinase activity was high in developing stages and negligibly low in adults and showed specificity to L-dopa. Phenylalanine and tyramine are unaffected by tyrosinase. Blood feeding did not influence the activity of both these enzymes.

Animals

Relation of blood pressure to cognitive function in the elderly.

Clinical case-control studies of the relation between blood pressure and cognitive function have generally found lower function among hypertensives. Most of these studies were small and incompletely controlled for confounders. Two population-based studies have yielded conflicting results. This study examines cognitive function over the entire range of blood pressure in a defined elderly population. A questionnaire administered in the home to 3,809 persons aged greater than or equal to 65 years in East Boston, Massachusetts, in 1982 and 1983 contained four brief cognitive tests: immediate memory, delayed memory, a mental status questionnaire, and digit span. In linear regression analyses adjusting for age, sex, and education, the direction of the association was not consistent among the tests. An increase in diastolic pressure of 10 mmHg was associated with an increase of 1.0 in percentile scores on the immediate memory test (95% confidence interval (CI) -0.04 to 1.9); with an increase of 1.1 in percentile scores on the delayed memory test (95% CI -0.1 to 2.3); with a decrease of -0.8 in percentile scores on the mental status questionnaire (95% CI -1.8 to 0.2); and with a decrease of -0.9 in percentile scores on the attention test (95% CI -1.5 to -0.2). These results suggest that blood pressure is not a substantial contributor to cognitive status in the elderly.

Aged

Risk of death from Alzheimer's disease in a community population of older persons.

A random sample of 467 persons over age 65 years from the population of an urban US community, stratified by age, sex, and performance on a brief memory test, underwent clinical evaluation for dementing illness in 1982-1984. Of these persons, 134 had probable Alzheimer's disease, 166 had possible Alzheimer's disease, and 167 had no evidence of Alzheimer's disease. Over a median follow-up period of 4.9 years following evaluation, 165 (35%) died. Overall, persons with probable Alzheimer's disease had a relative risk of death 1.44 (95% confidence interval (Cl) 1.05-1.96) times that of the unaffected. Level of cognitive impairment and the presence of cachexia upon physical examination both strongly and independently modified risk of death. Among those with probable Alzheimer's disease, mortality for those with mild or moderate cognitive impairment and no evidence of cachexia was comparable to that of the unaffected. However, among those with probable Alzheimer's disease and either severe cognitive impairment or cachexia, the risk of death was substantially higher. Persons with probable Alzheimer's disease who had both severe cognitive impairment and clear cachexia had a risk of death 4.60 (95% Cl 1.63-13.1) times that of unaffected persons.

Aged

Peak expiratory flow rate and 5-year mortality in an elderly population.

During a population survey in 1982-1983 among all community-dwelling elderly aged 65 years and over in East Boston, Massachusetts, measurements of peak expiratory flow rate using the mini-Wright peak flow meter were made on 3,582 participants (80% of those eligible). The average peak flow rate was 315 liters/minute, and a measure of peak flow rate adjusted for age, sex, height, and weight was computed. This was a highly significant (p less than 0.0001) predictor of 5-year total mortality, whose ascertainment was virtually complete. The relative risk was 1.27 (95 percent confidence interval 1.19-1.36) per 100 liters/minute decrease in peak flow rate, using a proportional hazards model including terms for age, sex, and smoking. There was no apparent modification of the effect of this measure in various categories of smoking, with relative risks of 1.24 for nonsmokers, 1.29 for ex-smokers, and 1.26 for current smokers. This finding also persisted after adjustments for other covariates, including respiratory symptoms such as cough, phlegm, and wheeze; cardiovascular risk factors such as history of myocardial infarction and stroke; and systolic and diastolic blood pressures; socioeconomic status; scores on simple tests of cognitive function; measures of physical activity and functional ability; and self-assessed state of health. In a stepwise model including all of these variables, the relative risk was 1.16 (p less than 0.0001) per 100 liters/minute decrease in peak flow rate, indicating that peak flow rate is a strong independent predictor of total mortality in the elderly.

Activities of Daily Living

Evidence of genetic recombination in Leishmania.

In the genus Leishmania there has been no convincing demonstration of genetic exchange, and it has been proposed that reproduction is clonal. However, preliminary characterization of two strains of Leishmania isolated from wild animals in a zoonotic focus of cutaneous leishmaniasis in the Eastern Province of Saudi Arabia, has suggested that they may represent hybrids of Leishmania major and Leishmania arabica. Evidence presented here strongly supports this hypothesis. Isoenzyme analysis and molecular karyotyping of cloned organisms indicated that the putative hybrids are distinct from other species of Leishmania, and possess characteristics of both L. major and L. arabica. Experiments using highly specific probes demonstrated that kinetoplast minicircle DNA from the putative hybrid contained L. major-specific, but not L. arabica-specific sequences. DNA fingerprinting data obtained using 6 genomic DNA probes were consistent in all cases with a L. major/L. arabica recombinant genotype, and implied both diploidy and allelic segregation. These observations suggest that sexual reproduction may generate genetic diversity within natural Leishmania populations.

Animals