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PubMed1999

Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race.

BACKGROUND: Werner syndrome (WS), an autosomal recessive disease characterized by premature aging, has a high frequency of association with six rare neoplasms in Japanese patients, and only four of these neoplasms also occur excessively in whites. Several differ from what is usual in their epidemiology and/or histology. Described in this article are peculiarities in the occurrences of follicular and papillary thyroid carcinomas among Japanese patients and the possible genotype-phenotype relations pertaining to cell types and the absence of excess thyroid carcinoma occurrence in whites with WS. METHODS: Epidemiologic features of 23 histologically diagnosed thyroid carcinomas from a series of 150 cancers in 845 Japanese patients with WS were compared with those of 19,446 tumors in a Japanese national registry of thyroid carcinomas from 1977-1991. Germline mutations had been determined by molecular studies of peripheral blood. RESULTS: The average age of patients with thyroid carcinoma was 39 years for those with WS and 49 years for the registry patients. The female-to-male ratios were 2.3:1 and 6.6:1, respectively. The rates of occurrence of papillary, follicular, and anaplastic carcinomas were 35%, 48%, and 13% for Japanese patients with WS and 78%, 14%, and 2% in the general Japanese population. All four cases of follicular carcinoma had germline mutations of the WS gene in the C-terminal region, and the germline mutation for the only papillary carcinoma was in the N-terminal region. CONCLUSIONS: This study suggests two possible WS genotype-phenotype relations. One concerns thyroid carcinoma histology; the other concerns frequent mutations that occur in the C-terminal region in Japanese patients, but not in white patients, with WS. These may account for the excess thyroid carcinoma occurrence among Japanese.

Adenocarcinoma, Follicular↗

PubMed1999

Epidemiology and genetic theories in the etiology of congenital talipes equinovarus.

The exact genetic mechanism of inheritance of congenital talipes equinovarus (CTEV) has been extensively investigated using family studies and other epidemiological methods, but to date no conclusive result has been reached. This may be due to the presence of a number of inheritance patterns, a number of different etiologies presenting as the same morphological condition, or complex gene-environment interactions. Indeed, a number of epidemiological factors have also been implicated in the etiology. While epidemiological studies can suggest inheritance patterns, only by identification of specific genes, can inheritance patterns be proven. This article reviews the epidemiological work on the etiology of CTEV and discusses some of the epidemiological principles involved.

Clubfoot↗

PubMed1986

Public health implications of carcinogenic exposure under the multistage model.

Mathematical implications of the multistage model of carcinogenesis are developed in order to answer important quantitative questions about environmentally induced cancer from the perspective of public health and intervention. Excess cancer incidence due to constant and interval exposure is examined theoretically for a stationary population under the multistage model of Armitage and Doll (Br J Cancer 1954;8:1-12). The time patterns for excess population incidence are simulated for the two types of exposure and the particular cellular change affected by the carcinogen. It is shown that the cumulative excess population incidence does not depend on which cellular change is induced by exposure and increases linearly with exposure duration. However, agents which affect earlier stages induce cancers which appear later in the population and, as a result, their detection by epidemiologic methods may be expected to occur later. Thus, such agents are more dangerous since control measures may be delayed, allowing greater cumulative incidence.

Carcinogens↗

PubMed2004

[Epidemiology of lipid profile of the Spanish elderly population: the EPICARDIAN study].

BACKGROUND AND OBJECTIVE: The aim of this study was to describe the lipid profile, the levels of serum total cholesterol (TC), LDL cholesterol (C-LDL), HDL cholesterol (C-HDL) and triglyceride (TG), to compare these levels between geographical areas and to estimate the prevalence of dyslipidemia in elderly residents (65 years and older) from urban and rural areas of Spain. PATIENTS AND METHOD: Epidemiological, observational, multicentre study of Spanish elderly people residents (>or= 65 years old) of 3 communities in 3 Spanish regions: Arévalo (Avila) and Begonte (Lugo) as rural areas and Lista (Central Madrid) as urban area. Stratified randomized sample by age and sex from population census of each area. The participation rate was: 84.6%. At-home interviews (phase 1) (n = 4522): with determination of capillary blood cholesterol levels (Reflotron) and clinical visit (phase 2) (1/3 selected randomly, n = 1907): determination of serum TC levels (enzymatic colorimetric method CHOP-PAD), C-HDL, C-LDL (Friedewald equation) and TG (Trinder Method). RESULTS: Mean concentrations of TC was 230.3 (46.8) mg/dl. These levels decreased significantly with increasing age (p < 0.001), higher in women (p = 0.001); lower in Lugo (226.4 [49.7] mg/dl) than in Madrid (233.2 [42.3] mg/dl) and Arévalo (236.5 [43] mg/dl) (p = 0.002). Global prevalence of hypercholesterolemia by SEA simplified criteria was: 68.9% (95% confidence interval, 66.8-71). Mean concentrations of C-LDL was: 159.4 (37.9) mg/dl; C-HDL: 48.2 (15) mg/dl, and TG: 119.7 (63.85) mg/dl. 31% of cases were awarded about the hypercholesterolemia. Only 30% of them were under treatment with lipid lowering drugs; and 30% of the subjects showed CT concentrations < 200 mg/dl, with no differences by sex, age, study area or education level. Female sex, urban habitat and hypertension were the only variables independently associated to hypercholesterolemia in the logistic model. CONCLUSIONS: The prevalence of dyslipidemia is slightly higher to SEA estimation for the European elderly population (50%), greater in women and in younger groups. The awareness, treatment and control of hypercholesterolemia are low among the Spanish elderly population.

Aged↗

PubMed1998

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures.

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)

Air Pollution↗

PubMed1989

On statistical methods for analysing the geographical distribution of cancer cases near nuclear installations.

There is great public concern, often based on anecdotal reports, about risks from ionising radiation. Recent interest has been directed at an excess of leukaemia cases in the locality of civil nuclear installations at Sellafield and Sizewell, and epidemiologists have a duty to pursue such information vigorously. This paper sets out to show that the epidemiological methods most commonly used can be improved upon. When analysing geographical data it is necessary to consider location. The most obvious quantification of location is ranked distance, though other measures which may be more meaningful in relation to aetiology may be substituted. A test based on distance ranks, the "Poisson maximum test", depends on the maximum of observed relative risk in regions of increasing size, but with significance level adjusted for selection. Applying this test to data from Sellafield and Sizewell shows that the excess of leukaemia incidence observed at Seascale, near Sellafield, is not an artefact due to data selection by region, and that the excess probably results from a genuine, if as yet unidentified cause (there being little evidence of any other locational association once the Seascale cases have been removed). So far as Sizewell is concerned, geographical proximity to the nuclear power station does not seem particularly important.

Cluster Analysis↗

PubMedDate not supplied

The development of persistent pain and psychological morbidity after motor vehicle collision: integrating the potential role of stress response systems into a biopsychosocial model.

OBJECTIVES: Persistent pain and psychological sequelae are common after motor vehicle collision (MVC), but their etiology remains poorly understood. Such common sequelae include whiplash-associated disorders (WAD), fibromyalgia, and posttraumatic stress disorder (PTSD). Increasing evidence suggests that these disorders share overlapping epidemiologic and clinical features. A model is proposed in which central neurobiological systems, including physiologic systems and neuroanatomical structures involved in the stress response, are an important substrate for the development of all 3 disorders and interact with psychosocial and other factors to influence chronic symptom development. METHODS: Epidemiologic and clinical characteristics regarding the development of these disorders after MVC are reviewed. Evidence suggesting a role for stress response systems in the development of these disorders is presented. RESULTS: Contemporary evidence supports a model of chronic symptom development that incorporates the potential for interactions between past experience, acute stress responses to trauma, post-MVC behavior, and cognitive/psychosocial consequences to alter activity within brain regions which process pain and to result in persistent pain, as well as psychological sequelae, after MVC. Such a model incorporates factors identified in prior biopsychosocial theories and places them in the landscape of our rapidly developing understanding of stress systems and CNS pain-modulating pathways. CONCLUSION: New models are needed to stimulate deeper examination of the interacting influences of initial tissue damage, acute pain, psychosocial contingencies, and central stress pathways during chronic symptom development after MVC. Deeper understanding could contribute to improved treatment approaches to reduce the immense personal and societal burdens of common trauma-related disorders.

Accidents, Traffic↗

PubMed1999

Weighing the risks and benefits of vaccination.

The following summarizes this author's current thoughts regarding veterinary vaccines and their safety: 1. Every licensed animal vaccine is probably effective, but also produces some adverse effects. 2. Prelicensing studies of vaccines are not specifically designed to detect adverse vaccine reactions. 3. An improved system of national postmarketing surveillance is required to identify most adverse vaccine reactions that occur at low and moderate frequency. 4. Even a good postmarketing surveillance system is unlikely, however, to detect delayed adverse vaccine reactions, and the longer the delay the less likely they will be associated with vaccination. 5. Analytic epidemiologic (field) studies are the best way to link vaccination with delayed adverse reactions, but these are often hindered by incomplete vaccination histories in medical records in veterinary practice and by a lack of veterinarians in industry trained in epidemiologic methods. 6. Each licensed veterinary vaccine should be subjected to a quantitative risk assessment, and these should be updated on a regular basis as new information becomes available. 7. Risk assessment should be used to identify gaps in information regarding the safety and efficacy of vaccines, and appropriate epidemiologic studies conducted to fill these gaps that contribute to the uncertainty in risk estimates. 8. Risk assessment is an analytical process that is firmly based on scientific considerations, but it also requires judgments to be made when the available information is incomplete. These judgments inevitably draw on both scientific and policy considerations. 9. Representatives from industry, government, veterinary medicine, and the animal-owning public should be involved in risk management, that is, deciding between policy options. The controversy regarding vaccine risks is intensifying to the point that some animal owners have stopped vaccinating their animals. They offer as justification the belief that current vaccines are "just too dangerous." Some owners report that since they completely stopped vaccinating their animals, they have been healthy. What they fail to realize is that a high percentage of animal owners are responsible and do vaccinate their animals, thus providing "herd immunity" protection to the unvaccinated animals whom they contact. The solution to the vaccine controversy is not to abandon vaccination as an effective means of disease prevention and control, but rather to encourage vaccine research to answer important questions regarding safety and to identify the biological basis for adverse reactions. Key questions to be answered include these: What components of vaccines are responsible for adverse reactions? What is the genetic basis for susceptibility to adverse health effects in animals? How can susceptible individuals be identified? Do multivalent vaccines cause a higher rate of adverse reactions than monovalent vaccines? Is administration of multiple doses of monovalent vaccines really any safer than administering a single multivalent vaccine? These and other vaccine-related questions deserve our attention as veterinarians so we can fulfill our veterinary oath to relieve animal suffering and "above all else, do no harm."

Animal Diseases↗

PubMed2000

Genetic epidemiologic studies on age-specified traits. NIA Aging and Genetic Epidemiology Working Group.

This commentary calls attention to the value of combining genetic and epidemiologic methods in studies to understand the determinants of two crucial aspects of aging: ages at which certain outcomes (e.g., disease, mortality) occur and rates of change with age of individual's characteristics (e.g., physiologic functions, disease risk factors). Inclusion of age in the specification of traits in genetic epidemiologic studies could lead to improved strategies to increase healthy life expectancy and evaluate individuals' risk for age-related morbidity. Special issues that make genetic epidemiologic approaches important for studies of age-specified phenomena as well as opportunities and challenges for such studies are discussed, including study designs, sampling frames, databases, analytic tools, and related methodological issues. This commentary is based on a report prepared by the Aging and Genetic Epidemiology Working Group, convened by the National Institute on Aging to review opportunities for research on the genetic epidemiology of aging-related outcomes. The report, which contains more extensive discussion, literature review, and references, is available on the World Wide Web at http://www.nih.gov/nia/conferences/GeneticReport111199.htm.

Age Factors↗

PubMed2005

Molecular typing of Mycobacterium tuberculosis by mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis, a more accurate method for identifying epidemiological links between patients with tuberculosis.

IS6110 fingerprinting of Mycobacterium tuberculosis is the standard identification method in studies on transmission of tuberculosis. However, intensive epidemiological investigation may fail to confirm transmission links between patients clustered by IS6110-restriction fragment length polymorphism (RFLP) typing. We applied typing based on variable numbers of tandem repeats (VNTRs) of mycobacterial interspersed repetitive units (MIRUs) to isolates from 125 patients in 42 IS6110 clusters, for which thorough epidemiological data were available, to investigate the potential of this method in distinguishing epidemiologically linked from nonlinked patients. Of seven IS6110 clusters without epidemiological links, five were split by MIRU-VNTR typing, while nearly all IS6110 clusters with proven or likely links displayed conserved MIRU-VNTR types. These results provide molecular evidence that not all clusters determined on the basis of multibanded IS6110 RFLP patterns necessarily reflect transmission of tuberculosis. They support the use of MIRU-VNTR typing as a more reliable and faster method for transmission analysis.

Bacterial Typing Techniques↗

PubMed2000

New research directions in neuroepidemiology.

Many of the risk factors previously identified for disorders such as Alzheimer's disease, periventricular leukomalacia, multiple sclerosis, stroke, cerebral palsy, mental retardation, and acquired learning and attention disorders ultimately may be shown to damage the central and peripheral nervous systems through activation of inflammatory mediators. The challenge to epidemiologists in the future is to expand use of epidemiologic methods to explore how immune-mediated insults produce CNS disorders in human populations. Studies of the association of use of nonsteroidal anti-inflammatory drugs with risk of Alzheimer's disease and those of the association of immune parameters with risk of cerebral palsy are excellent examples of how epidemiology can contribute to our understanding of the causes of neurologic and/or neurodevelopmental disorders. Many of the immune parameters of interest have short half-lives and are difficult to measure outside of the laboratory setting. Questions also remain as to the proper timing of measurements in relation to the initial insult and, in some cases, which tissue is the most appropriate to sample. These measurement issues will need to be resolved before use of immune biomarkers in epidemiologic studies of the etiologies of neurologic disorders can be fully realized. Epidemiologists are most likely to help identify ways to prevent neurologic disorders if they are knowledgeable about the molecular biology of inflammation, modulators of CNS vulnerability, and genetic polymorphisms that influence both inflammation and CNS vulnerability and are prepared to become adept at biomarker epidemiology. This does not necessarily compel them to gain extensive knowledge of neurobiology. Rather, neuroepidemiology in the 21st century will require increased collaboration between epidemiologists, neurologists, and neurobiologists.

Aged↗

PubMed2001

[Increase in the prevalence of Echinococcus multilocularis infection in red foxes in Lower Saxony].

Echinococcus multilocularis is a tapeworm having carnivores as final hosts, the red fox in particular, dog and cat less frequent. Its two host life cycle consists of a larval cycle which predominantly takes place in the liver of rodents such as mice but it can also develop in musk rats as intermediate hosts. Man can also be infected and serves as a wrong intermediate host. He develops an alveolar echinococcosis which usually ends lethal without medical treatment. The prevalence of E. multilocularis among 5.365 red foxes in Lower Saxony was monitored from 1991 to 1997. The data were analysed using spatial epidemiological methods. This evaluation is based on a significance test which was applied to the parameters of spatial autoregressive regression models (CAR) fitting to the data of two successive sampling periods from 1991-1994 and 1994-1997. The mean prevalence (spatial median) increased from 6% to 11%. The results of this epidemiological study which was restricted to Lower Saxony support for the first time the earlier reported assumption that the prevalence of foxes infected with E. multilocularis has risen in Europe in the last decade. The reasons for this development are still unknown.

Animals↗

PubMed2005

[The tuberculosis monitoring system in Moscow].

The existing need for objective assessing methods of different reform strategies in the health care system and of the epidemic situation has resulted in the setting-up of monitoring systems as the most efficient and rapid tool to solve health care problems on the evidence basis provided that the primary data are highly valid. Clinical epidemiological methods with monitoring results kept in mind make it possible to search for the optimum approaches to achieving a qualitative, accessible, and effective program for health care delivered to the population. The tuberculosis monitoring system to be introduced in Moscow can pool an information flow at the urban level, furnishes an opportunity to analyze and assess the activities of a phthisiological service, makes it possible to obtain pooled data on areas, to assess the epidemic situation and tuberculosis-controlling work, and to work out and implement antiepidemic measures.

Adolescent↗

PubMed1984

[Mapping method in the epidemiological study of infections and infestations. II. Soil characteristics in localities permanently at risk for anthrax].

Investigations carried out with the use of the mapping method have revealed that the distribution of localities with stationary unfavorable situation in anthrax throughout the area is linked with the agrochemical properties of soils. The number of the foci of anthrax on neutral and weakly alkaline soils has proved to be considerably higher than in soils with low pH values. No relationship between the content of humus in soils and the distribution of localities with stationary unfavorable situation in anthrax throughout the area has been detected. The results of investigations carried out with the use of the mapping method permit experts to make forecasts and to examine the ecological aspects of the projects carried out in the area.

Agriculture↗

PubMedDate not supplied

Training and service in public health practice, 1951-90--CDC's Epidemic Intelligence Service.

The Epidemic Intelligence Service (EIS) was created at the Centers for Disease Control (CDC) in 1951 as a combined training and service program in the practice of applied epidemiology. Since 1951, more than 1,700 professional have served in this 2-year program of the Public Health Service. In the decade of the 1980s, EIS underwent dramatic changes in response to the increased breadth of the CDC mission and the rapid expansion of epidemiologic methods. Modifications in the experience of an EIS Officer have resulted from the increased need for more sophisticated analytic methods and the use of microcomputers, as well as CDC's expanded mission into chronic diseases, environmental health, occupational health, and injury control. Officers who have entered the EIS in the past decade tend to be older than their predecessors, tend to enter the program with more experience and training in epidemiology, and are more likely to stay in public health either at the Federal level or in State and local health departments. The EIS Program continues to be a critical source for men and women to respond to the need and demand for epidemiologic services both domestically and internationally.

Centers for Disease Control and Prevention, U.S.↗

PubMed1989

Assessing risks and preventing disease from environmental chemicals.

In the last 25 years there has been considerable concern expressed about the extent to which chemical agents in the ambient and work environments are contributing to the causation of disease. This concern is a logical extension of our increased knowledge of the real and potential effects of environmental chemicals and the methodological difficulties in applying new knowledge that could help prevent environmentally induced disease. Chemical risk assessment offers an approach to estimating risks and involves consideration of relevant information including identification of chemical hazards, evaluation of the dose-response relationship, estimation of exposure and finally, risk characterization. Particularly significant uncertainties which are inherent in use of this and other risk models include animal-human and low dose-high dose extrapolation and estimation of exposure. Community public health risks from exposure to environmental chemicals appear to be small relative to other public health risks based on information related to cancer trends, dietary intake of synthetic chemicals, assessment data on substances such as DDT and "dioxin," public health effects of hazardous waste sites and contextual considerations. Because of inherent uncertainty in the chemical risk assessment process, however, we need to apply what methods are available in our efforts to prevent disease induced by environmental chemicals. There are a number of societal strategies which can contribute to overall reduction of risk from environmental chemicals. These include acquisition of information on environmental risk including toxicity, intensity and extensity of exposure, biological monitoring, disease surveillance, improvement in epidemiological methods, control of environmental chemical exposures, and dissemination of hazardous chemical information. Responsible environmental risk communication and information transfer appear to be among the most important of the available strategies for preventing disease induced by chemicals in the environment.

Communication↗

PubMed1990

[Varicose veins and chronic venous insufficiency--minor disorder or disease? A critical review of the literature].

The controversial question of the incidence and significance of varicoses and chronic venous insufficiency is analysed by a critical review of epidemiological studies. It is seen that many of the results which initially appear to diverge are attributable to different, in part unsatisfactory epidemiological methods; e.g. patient groups of different ages and sex, different interview and examination techniques in addition to, above all, different weighting of varicosis. Thus, studies in general practice showed that the prevalence for varicoses in women was four times that in men; CVI was, in fact, 15 times more frequent than in epidemiological studies. The different weighting of varicoses and chronic venous insufficiency may well be one of the major reasons for the absent "unité de doctrine".

Cross-Sectional Studies↗

PubMed1997

[The cognitive role of epidemiology and its pitfalls].

One of the most important roles of epidemiology is to seek causes of diseases. The causality in medicine is a difficult philosophical category which requires deep ontological thinking and a thorough methodological preparation. If this condition is not met, various misunderstandings and errors develop with serious consequences for clinical practice. In recent medical literature we find many controversial views which are abused by the press and cause mistrust of the public to medical science and attract patients to the dubious practices of alternative medicine. It is therefore the duty of research workers to pay more attention to modern epidemiological methods and their philosophy. The predominating pluricausal model of risk factors is recently criticized because of its excessive simplicity. reductionism and dualism which separates health from disease. The need arises of a new universal model of health where the dominant position will be held by social environmental, behavioral and psychological aspects. Modern epidemiology needs not only a correct methodology but also a proper theory.

Causality↗