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Biomedical subjects

W F Page

Publications and source records attributed to W F Page.

At least 37 records · Page 2Linked to original sources

Importance of cerebrovascular disease in studies of myocardial infarction.

BACKGROUND AND PURPOSE: Myocardial infarction and stroke are both predominantly manifestations of atherosclerosis, yet stroke is commonly ignored in prognostic studies and therapeutic trials of ischemic heart disease. Our objective was to assess, in a community setting, the relative importance of stroke among patients at high risk for myocardial infarction. METHODS: We analyzed 1985 survey data from the National Academy of Science Twin Registry of white male veterans. To minimize confounding by genetic and environmental factors, we restricted our analysis to the rates of stroke and myocardial infarction among monozygotic twins counted as individuals or as twin pairs. RESULTS: Among 2764 monozygotic twins aged 58 to 68 years, the overall rate of myocardial infarction was 10% and stroke 3.1%. Among 2632 individual monozygotic twins (95%) with complete responses, the rate of stroke among men with a history of myocardial infarction was 7.5% (17/228) compared with 2.4% (58/2404) among those without myocardial infarction (odds ratio = 3.3, chi square 2 = 19.1, P<.001). A strong association between stroke and myocardial infarction was also found when the data were analyzed for twin pairs (chi square 2 = 135, P<.0005). CONCLUSIONS: Our results suggest that stroke, in addition to myocardial infarction, should be considered as an outcome in clinical investigations of ischemic heart disease.

Aged↗

Prevalence of a history of testicular cancer in a cohort of elderly twins.

Prior studies have suggested that the risk of testicular cancer among dizygotic twins may exceed that among monozygotic twins or the general population. Cryptorchidism is associated with testicular cancer and twinship, and therefore might potentially explain the findings of the prior studies. In 1993-1994, when they were 66 to 77 years of age, 14,326 twin individuals in the National Academy of Sciences-National Research Council Twin Registry were interviewed by telephone. A history of testicular cancer was reported by 5 (0.08%) of 5951 monozygotic twins and 11 (0.16%) of 6992 dizygotic twins. Follow-up interviews concerning testicular cancer risk factors and treatment were able to be administered to 4 of the monozygotic and 9 of the dizygotic twins reporting testicular cancer. A history of cryptorchidism was reported in the follow-up interview by only one dizygotic twin. Our data agree with the results of prior studies reporting a more frequent occurrence of testicular cancer among dizygotic than monozygotic twins. Although somewhat limited by small numbers, our study also suggests that the findings of increased testicular cancer in dizygotic twins are not explained simply by increased occurrence of cryptorchidism in twins.

Aged↗

Epidemiology of multiple sclerosis in US veterans. 6. Population ancestry and surname ethnicity as risk factors for multiple sclerosis.

Previously, we studied the effect of population ancestry on the risk of multiple sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census ancestry data with MS case/control ratios. Here, the joint effects of population ancestry and surname-derived ethnicity on MS risk are examined in the same series. Census data are used again to characterize the population ancestry of the state from which each subject entered active duty (EAD)--that is, the proportions of the populace reporting various ancestries--and subjects were also individually categorized into a single ethnic group, without knowledge of case/control status, based on surname. In this study population, categorized ethnicity was strongly correlated with population ancestry, as expected. Although univariate analyses showed statistically significant associations between MS risk and several surname-derived ethnicities and ethnic groups, when residence at EAD was accounted for as well, there was almost no ethnic variation in MS risk. A logistic regression analysis further showed that variations in MS risk are associated most strongly with latitude and population ancestry group; in particular, subjects who entered military service from states with higher proportions of Swedish or French ancestry had higher risks of MS. After adjustment for characteristics of place, the only significant individual ethnicity factor found was Southern European ethnicity. In general, we conclude that an individual's ethnicity seems to be of less relative importance in determining MS risk than is the population ancestry of the state of EAD. These findings underscore the fact that MS is a disease of place, with 'place' including not only attributes of the locale (e.g., latitude), but also of its populace (e.g., ancestry).

Adult↗

Intelligence and education as predictors of cognitive state in late life: a 50-year follow-up.

We evaluated the relation of education and intelligence in early adult life to cognitive function in a group of elderly male twins. The Army General Classification Test (AGCT) was administered to US armed forces inductees in the early 1940s. Fifty years later, as part of a study of dementia in twins, we tested the cognitive status of 930 of these men using the modified Telephone Interview for Cognitive Status (TICS-m). TICS-m scores obtained in later life were correlated with AGCT scores (r = 0.457) and with years of education (r = 0.408). Thus, in univariate analyses, the AGCT score accounted for 20.6% and education accounted for 16.7% of variance in cognitive status. However, these two effects were not fully independent. A multivariable model using AGCT score, education, and the interaction of the two variables as predictors of the TICS-m score explained 24.8% of the variance, a slightly but significantly greater proportion than was explained by either factor alone. In a separate analysis based on 604 pairs of twins who took the AGCT, heritability of intelligence (estimated by AGCT score) was 0.503. Although this study does not address the issue of education and premorbid IQ as risk factors for dementia, the findings suggest that basic cognitive abilities in late life are related to cognitive performance measures from early adult life (ie, education and IQ).

Aged↗

Self-reported alcohol intake and cognition in aging twins.

OBJECTIVE: To determine the relationship between long-term alcohol intake and cognitive functioning in aging Caucasian men. METHOD: A retrospective cohort and co-twin-control study of self-reported alcohol intake and cognitive testing using the National Academy of Sciences-National Research Council (NAS-NRC) Twin Panel of U.S. veterans (born between 1917 and 1927). The study included 4,739 twins with two self-reported drinking histories (1970s and 1980s) and a telephone mental status interview (1990 and 1991) that also included 145 individuals with a diagnosis of alcoholism. RESULTS: Age and education adjusted cognitive scores were lower (p < .05) in diagnosed alcoholics than in the remainder of the subjects. To compare age and education adjusted cognitive scores in alcohol intake, the 4,739 twins were divided, based upon questionnaire data, into nondrinkers and 5 quintiles of drinkers by average reported drinks of alcohol weekly (< 1.0, 1-3.3, 3.4-8.1, 8.2-16.0, > 16.0). Past drinkers had scores lower (p < .05) than nondrinkers and all but quintiles 1 and 5 of the drinkers. The light drinkers in quintile 1 and the heavy drinkers in quintile 5 scored lower (p < .05) than the moderate drinkers in quintile 4. Monozygotic twins in quintile 4 scored higher (p < .05) than their co-twins in quintiles 1-3. CONCLUSIONS: No evidence was found to indicate an association between moderate long-term alcohol intake and lower cognitive scores in aging individuals. There was a suggestion of a small protective effect of past moderate alcohol intake on cognitive function with aging.

Aged↗

World War II-veteran male twins who are discordant for alcohol consumption: 24-year mortality.

The role of genetic and shared environmental influences in the association of alcohol with mortality was studied by using the National Academy of Sciences-National Research Council World War II-veteran male twin registry. An epidemiologic questionnaire administered from 1967 through 1969 permitted identification of twin pairs discordant for alcohol consumption. The subsequent 24 years of mortality follow-up yielded data on time and cause of death. Analyzing the first or only death in drinking-discordant pairs, we observed 27 deaths in abstainer twins and 14 deaths in their light- to moderate-drinker cotwins (relative risk [RR] = 1.93). Excess mortality in twin abstainers was also indicated for deaths from cardiovascular diseases (RR = 2.0) and other causes of death excluding cancers (RR = 3.2). The protective effect, however, of light to moderate drinking did not persist in twins who were smokers at baseline.

Alcohol Drinking↗

Ascertainment of mortality in the U.S. veteran population: World War II veteran twins.

Veterans now make up nearly two-thirds of U.S. males aged 65 and older, and thus medical research in the male geriatric population is largely concerned with veterans, whose mortality experience assumes greater importance as they age. Department of Veterans Affairs (VA) records provide an effective and efficient means of gathering information on mortality of veterans, but are useful only if they provide relatively complete ascertainment. We investigated the completeness of VA death reporting (via the Beneficiary Identification and Records Locator Subsystem [BIRLS]) in a large cohort of nearly 32,000 World War II veteran twins followed from 1946 through 1990, comparing VA and Social Security Administration (SSA) mortality ascertainment. The small number of additional deaths found using SSA records--roughly 3% of total deaths--provides evidence that VA death reporting was nearly complete. A further capture-recapture analysis, assuming independence of BIRLS and SSA mortality ascertainment, indicated that BIRLS ascertainment was 95.4% complete.

Aged↗

Genetic component of lung cancer: cohort study of twins.

Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15,924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur.

Adult↗

Malnutrition and subsequent ischemic heart disease in former prisoners of war of World War II and the Korean conflict.

The harsh treatment of former prisoners of war (POWs) of World War II and the Korean conflict resulted in severe malnutrition. Although rarely linked to specific long-term medical problems, a specific marker of malnutrition, self-reported lower limb edema (presumably due to a vitamin B deficiency) was associated with a three-fold increase in subsequent death attributed to ischemic heart disease (IHD) during the follow-up period from 1967 through 1975. Although there is at present no medical basis for linking edema, which is perhaps a marker for some unmeasured risk factor, to subsequent IHD, this finding may nonetheless have medical implications for the group of former POWs and other populations with severe dietary deficiency. It also suggests there may be a need to reexamine currently held theories on malnutrition and subsequent chronic disease.

Edema↗

Concordance rates for benign prostatic disease among twins suggest hereditary influence.

OBJECTIVES: The etiology of benign prostatic hyperplasia (BPH) is unknown. Evidence for a hereditary trait would provide new avenues for investigation. METHODS: We compared the concordance for benign prostate disease in monozygotic (MZ) and dizygotic (DZ) twins who served in the United States military in World War II and have been followed by the Medical Follow-up Agency, Institute of Medicine of the National Academy of Sciences. Questionnaires completed in 1985 by 10,000 twins were reviewed for evidence of prostatic disease. Key words indicating benign prostatic disease (prostate, prostatectomy, BPH, TURP, and prostatism) were identified in 533 (5.3%) of the questionnaires. RESULTS: The average age was 64 +/- 3 years (range 56 to 68 in 1985). After eliminating men with known prostate cancer, there were 256 twin pairs that were informative for benign prostatic disease: both twins were concordant in 25 instances and discordant in 231, with only one twin mentioning benign prostatic disease. The pairwise concordance for MZ twins was 14.7% (19 of 129) and for DZ pairs it was 4.5% (5 of 112). The relative risk for benign prostatic disease for MZ twins was thus 3.3 (p = 0.008). The probandwise concordance rates, which express the probability of BPH in a cotwin of an affected twin, were 25.7% for MZ twins and only 8.5% for DZ twins. A covariance analysis estimated that 49% of the observed variance between twins could be attributed to genetic effects. CONCLUSIONS: These data provide preliminary evidence for the heritability of benign prostatic disease.

Aged↗

Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis.

Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancestry is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non-Scandinavian correlations may reflect predominantly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural environment, is part of the complicated picture of MS as a disease of place.

Analysis of Variance↗

Structural models of captivity trauma, resilience, and trauma response among former prisoners of war 20 to 40 years after release.

Long-term responses to captivity trauma were measured in a national sample of American former prisoners of war. Their responses included negative affect, positive affect, and somatic symptoms as assessed by the Cornell Medical Index in 1967 and the Center for Epidemiological Study Depression Scale in 1985. These responses were strongly associated with captivity trauma (as indexed by captivity weight loss, torture, and disease) and resilience (as indexed by age and education at capture). Symptoms reported in 1967 were related to symptoms reported in 1985, suggesting symptom stability. These results are consistent with a model of trauma response that incorporates both trauma exposure and individual resilience. The findings are interpreted within a theoretical view of trauma response as adaptive when viewed from an evolutionary perspective.

Aged↗

Forty-five year follow-up after uninephrectomy.

This study examined the consequences of nephrectomy in United States Army personnel who lost a kidney due to trauma during World War II (WWII). Records of 62 servicemen who underwent nephrectomy at an average age of 25 years were obtained. Mortality was compared with that of WWII servicemen of the same age. Medical records of 28 deceased subjects were reviewed for evidence of kidney disease. Medical histories were obtained and blood pressure and kidney function were assessed in 28 living subjects. Two subjects could not be located, and four subjects declined to participate. Mortality at 45 years was not increased in nephrectomized subjects. Kidney disease present in six of 28 deceased subjects was attributable to causes other than prior nephrectomy. Glomerular sclerosis was not increased in 10 subjects who had autopsy examinations. The prevalence of hypertension was not increased in living subjects. Five of 28 living subjects had abnormal renal function manifested by proteinuria greater than 250 mg/day in four cases (range: 377 to 535 mg/day) and serum creatinine levels greater than 1.5 mg/dl in three cases (range: 1.7 to 1.9 mg/dl). Conditions other than nephrectomy could have contributed to impairment of renal function in each of these subjects. These findings suggest that uninephrectomy in young adults has few major adverse consequences over 45 years.

Adult↗

Epidemiology of multiple sclerosis in US veterans. 4. Age at onset.

Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged 'service-connected' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales.

Adult↗

Waist/hip ratio, body mass index and premature cardiovascular disease mortality in US Army veterans during a twenty-three year follow-up study.

A retrospective longitudinal analysis of fat distribution and cause-specific mortality was performed on data from 105,062 men discharged from the United States Army in 1946-47. Baseline height, weight, waist and hip girth, and 23-year follow-up mortality data were available for 84,910 white men. Proportional hazard survival analysis was performed by 5-year age group for waist/hip ratio (WHR) and for body mass index (BMI) in prediction of time to death from ischaemic heart disease (IHD) and stroke. Relative risk of IHD fatality per standard deviation (s.d.) of WHR ranged from 1.11 to 1.17, the higher values appearing in younger age groups. Relative risk due to BMI was not significant in the group aged 16-20 years at time of discharge from service, but ranged from 1.22 to 1.25 per s.d. among the 21-30 year olds. WHR was predictive of cerebrovascular disease mortality among 16-25 year olds, carrying a relative risk of 1.24 to 1.35 per s.d. BMI was not predictive of cerebrovascular disease mortality in any age group. Multivariate models indicated that WHR and BMI were related to subsequent IHD independently of each other in most age groups. WHR and BMI both contribute to risk of premature IHD mortality and WHR to risk of cerebrovascular disease mortality in an initially relatively healthy population of young men, although the effects are not equivalent in all age groups.

Adipose Tissue↗