Integrated Medical Education Resources: 091025P - ABSTRACTS FOR WORKSHOP ON ESSENTIALS OF EPIDEMIOLOGY IN PUBLIC HEALTH: MODULE ON EXPOSURE EPIDEMIOLOGY

ENVIRONMENTAL EXPOSURES

Presented at an Interactive Workshop on Essentials of Epidemiology in Public Health at the Department of Social and Preventive Medicine University Malaya Kuala Lumpur Malaysia 19-25 October 2009 by Professor Omar Hasan Kasule Sr MB ChB (MUK), MPH (Harvard), DrPH (Harvard) Professor King Fahad Medical College Riyadh; Professor of Epidemiology and Islamic Medicine Institute of Medicine University Brunei Darussalam, Visiting Professor of Epidemiology University of Malaya

THE ENVIRONMENTAL PROBLEM

Environmental epidemiology studies causes and prevention of environmental disease. The environment can be physical, chemical, biological, social, political, and cultural. Environmental hazards enter the body through the respiratory tract, the alimentary tract, and the skin. Most environmental exposures are involuntary. The objective is to eliminate a hazard or set a safe exposure limit. Environmental hazards are either natural or are a result of human activity. They may be natural disasters (earthquakes, cyclones), biological hazards (infections), chemical hazards, or physical hazards (extremes of temperature, noise, vibration, electrical). Population increase causes environmental degradation (more waste, more pollution) if the carrying capacity is not increased proportionately. The current problems facing the biosphere are: waste disposal, destruction of ecosystems, desertification, and depletion of the ozone layer due to release of chlorofluoro-carbons into the air. Chemical spills, earthquakes, floods, forest fires, landslides, and radioactive spills are environmental emergencies. Increasing industrialization is leading to ecological damage, exposure to chemical & physical hazards. Environmental effects of health are by carcinogenesis, teratogenesis, and toxicity.

ENVIRONMENTAL POLLUTION

Air pollution: The three commonest causes of air pollution are automobile emissions, fossil fuel energy plants, and industrial plants. The most pervasive air pollutants are CO, Pb, NO₂, SO₂, O₃, and particulate matters (gases, vapors, erosols, mist, dust, or smoke from industry, mining, or construction). Indoor pollution is either internal (cigarette smoke, heating, air-conditioning, asbestos, cooking, radon, carbon monoxide, formaldehyde, and nitrogen dioxide, organic and inorganic compounds, viruses, bacteria, and fungi.) or external (pollutants entering the house from the external atmosphere). The sources of outdoor pollution are: burning of coal or heavy oil, automobile emissions, and chemical industry emissions. Acute carbon monoxide (CO) exposure is fatal. Chronic CO exposure leads to angina and myocardial infarction. Asbestos causes lung cancer and mesothelioma. Auto emissions contain cancer-causing substances such as benzene (leukemia and aplastic anemia), and diesel (lung cancer). Environmental tobacco smoke (ETS), mainstream or side-stream smoke, is associated with lung cancer, heart disease, fetal & infant effects (intra-uterine growth retardation, low birth weight, preterm delivery, respiratory tract infection, behavioral and cognitive abnormalities). UV rays cause skin cancer, eye problems, genetic mutations, and disruption of the ocean food chains. Global warming results when greenhouse gases (CO₂, CFC, methane, and Nitrous oxide) prevent the re-radiation of infra-red (heat) into the atmosphere. It thaws polar ice leading to rising sea levels and higher temperatures. Photochemical smogs, commoner in valleys surrounded by mountains with no prevailing winds, are secondary pollutants produced when a primary pollutant like NO₂ reacts with sunlight. Acid rain is due to sulfur dioxide and nitrogen oxide mixing with water to form acids that fall with the rain. It causes acidification of the soil affecting crops and materials, killing marine life, erosion of buildings, and respiratory problems. Prevention of outdoor air pollution is by controlling or limiting industrial and car emissions. Prevention of indoor pollution is to change individual behavior involving proper ventilation, avoiding smoking, home testing for radon, and reducing indoor pollution.

Water pollution is due to municipal sewage or industrial pollutants. Water pollutants are organic wastes, infectious agents, synthetic organic compounds, inorganic chemicals, radioactive materials, oil spills, and heat. Water pollutants have been associated with cancer (asbestos, radon, arsenic, nitrites, and fluoride, and organic chemicals), adverse pregnancy outcome (LBW, spontaneous abortion, IUGR, congenital malformations) and infectious disease. Drinking water is purified by spray aeration, activated charcoal filtration, coagulation, flocculation, sedimentation, sand filtration, and disinfection (using chlorine, ozone, ultraviolet light, and iodine). Waste-water treatment is removal of pollution from wastes of industry or domestic sewage by sedimentation in ponds or tanks followed by decomposition by microorganisms and chlorination.

Soil pollution is by solid waste (residential, commercial, mining, industrial, municipal, and agricultural), hazardous waste (industrial and medical), or sewage. Solid waste is collection, compression to reduce volume, and disposal (sanitary land-fill, incineration, composting, recycling, and sea disposal). It is controlled by source reduction (recycling, less packaging), conservation (of natural resources and energy). Hazardous waste disposal is by secured landfills, deep well injection, incineration, and neutralization. It is controlled by source reduction (product substitution and using new processes) and treatment (biological, chemical, and physical). Sewage is waste water (domestic and industrial) and organic waste (human and animal). It has chemicals and pathogens that contaminate ground water. Its treatment is removing solids (sedimentation tanks), treating the organic material (microbial decomposition, biological oxidation using trickling filter systems, activated sludge processing, contact aeration, intermittent sand filters, and stabilization/oxidation ponds), and digesting the resulting sludge by anerobic organisms for volume reduction and change to inert substances. The solid and liquid effluents from treatment are disposed by spraying or spreading over the ground, burial underground or in landfills, disposal in surface water bodies, or use as fertilizers. Eco-poisons contaminate the air, water, food, and the soil but few studies have been undertaken about their chronic effects.

Eco-poisons can be medicinal agents, gases and volatile liquids (CO, cyanide, hydrocarbons), methanol and ethanol, corrosives (acids and alkalis, bleaches, disinfectants), pesticides (insecticides, herbicides, rodenticides, fungicides), poisonous plants and animals (eg venomous snakes), and metals. Pesticides poison children by accident and farm workers by occupational exposure. Pesticides are classified as soft or non-persistent (until 12 weeks), moderately persisting (1-8 months eg DDT, Aldrin, Dieldrin, HHC.) and hard or persistent (mercury, lead, arsenic and PCB). The effects of pesticides may be acute (headaches, rashes, weakness, dizziness, and fatigue) or chronic (cancer, mutations, birth defects, respiratory problems, convulsions, coma and death). Pesticide control is by education on safe use and safety regulations. Polychlorinated biphenyls (PCB) are wide-spread in the environment and enter ad\nd persist in the food chain. They cause rashes, headaches, nausea, diarrhea, alopecia, loss of libido, menstrual disorders, and fetal malformations. Food contamination is by microorganisms (S fecalis, S pyogenes, Salmonella spp., shigella spp., cholera, L. monocytogenes, viral hepatitis, and enteroviruses, S aureus, C. perfringes, C. welchii, C. botulism, E histolytica, T spiralis, Tenia spp., G lamblia, Toxoplasma spp.), chemicals (aluminium, arsenic, cadmium, chlorinated hydrocarbons, copper, lead, mercury, organic phosphates, PCBs, and zinc), food additives, and veterinary drugs (antibiotics and hormones given to animals), and plant products (aflatoxins, mycotoxins, enzyme inhibitors, phytohemagglutins, goitregens, cyanogens, pressor amines, oxalates, and fava beans).

EPIDEMIOLOGICAL STUDIES

Exposures can be single or mixed. Exposures can be measured as binary (yes/no) or on an ordinal scale. Exposures are described by their frequency, level of exposure, and whether there is a trend. Exposures can be measured directly by a personal monitor or indirectly by using environmental sampling. Exposures are measured using interview questionnaires, diaries, micro-environmental measurements, macro-environmental measurements, measurement of individual dose, measurement of individual doses, measurement of tissue concentration, and use of bio markers such as urinary metabolites, DNA adducts, and urinary adducts. Health effects can be produced by in an experimental system. Epidemiological studies may show an exposure-disease relation but with insufficient evidence. Some groups of humans have higher susceptibility. Morbidity, mortality, and cost are also measures of outcome. Confounding by age, gender, personal behavior, genetic makeup, present health status, and exposure to other pollutants, makes it difficult to pinpoint other health effects of specific exposures.

RISK ASSESSMENT and MANAGEMENT

Risk is the probability of an adverse outcome. Risk assessment is an analytic process of combining information on human exposure to environmental agents with data on health effects to produce the probability or frequency of health effects in a population. The objective of risk assessment is to find the optimum balance between risk and benefit, set target levels, and set priorities. Risk assessment / risk characterization has 4 components: hazard identification/assessment (using epidemiological and toxicological studies), dose response assessment (low to high dose extrapolations, and animal studies), exposure assessment, and risk determination. Hazard characterization involves assessment of dose response and susceptibility. Exposure assessment is carried out in the macro environment (air, water) or the micro environment (diet, smoke, alcohol etc). Risk determination involves prediction of risk beyond of risk beyond the range of empirical observation. Meta analysis and pooled analysis are used widely in risk analysis. Risk assessment uses both laboratory research data and field epidemiological data. Risk management is based on risk assessment reports. Risk assessment reports are speculative but it leads to regulatory action. Steps in the regulation of a hazard are: identification of the hazard, characterization of the hazard, and control of the hazard. Control is either by regulation or substitution. Communication of results of risk assessment to the general public is not easy.

Key Words and Terms: Acid Rain, Air Pollution, Dental Waste, Drug Residues, Eco-Poisons, Environmental Health, Environmental Degradation, Environmental Engineering, Environmental Ethics, Environmental Exposure, Environmental Health, Environmental Impact Analysis, Environmental Law, Environmental Medicine, Environmental Monitoring, Environmental Policy, Environmental Pollution, Environmental Protection, Food Microbiology, Food Parasitology, Green-House Effect, Hazardous Substance/Waste, Inhalation Exposure, Maternal Exposure, Maximum Permissible Exposure Level, Medical Waste, Natural Disasters, Noise And Vibration, Occupational Exposure, Paternal Exposure, Pest Control, Refuse Disposal, Smoke, Soil Pollution, Vehicle Emissions, Water Micro-Biology, Water Pollution.

OCCUPATIONAL EXPOSURES

INTRODUCTION

Data on occupational diseases is limited and is unreliable. There is in general low awareness of occupational disease. Job histories and exposures are difficult to document because they change often.

OCCUPATIONAL HAZARDS and DISEASES

Occupational hazards can be psychological stress, physical hazards (electrical, noise, radiological, temperature, vibration), chemical hazards, biological hazards, and ergonomical hazards. The major types of occupational diseases are: lung diseases (asthma, obstructive airway disease, granulomatous lung disease, chemical pneumonitis, bronchial asthma, and pneumoconiosis: asbestosis, byssinosis, silicosis, coal miner’s disease), cancer (lung cancer, leukemia, mesothelioma, bladder cancer, nose cancer, and liver cancer), skin diseases (dermatoses, dermatitis, pigmentation changes, spots, scleroderma, skin infections, contusions, electric burns, chemical burns), infectious diseases (acute hepatitis due to HBV, HIV, TB, anthrax, leptospirosis, and brucellosis), reproductive disorders (infertility, spontaneous abortion, teratogenesis, and low sperm counts due to exposure to lead and DBCP), musculoskeletal injuries (back, neck, and trunk disorders, the traumatic Raynaud’s phenomenon, bursitis, tenosynovitis, writer’s cramp, trigger finger, rotator cuff syndrome, carpal tunnel syndrome, and back pain), trauma (amputations, fractures, eye loss, lacerations, and traumatic deaths), neurological (peripheral nerve injury, toxic encephalitis), psychiatric disorders (psychoses and personality disorders) and noise injury (hearing loss and tinnitis), eye disorders (itchiness, or chemical burns due to chemical irritants, acids or alkali), and ENT disorders (rhinits, septal ulceration, and carcinoma).

OCCUPATIONAL HEALTH STUDIES

Occupational health studies can be clinical, epidemiological, and toxicological. Epidemiological studies investigate suspected hazards, determine quantitative relation between hazards and disease, and assess effectiveness of intervention. Study design can be cross-sectional, follow-up, and case control. Epidemiological analysis of population-based health data can be undertaken with useful results. A complete occupational history consists of: description of all jobs done, exposures at each job, time course of symptoms, similar symptoms in co-workers, and confounding exposures. Mortality studies are typically retrospective follow-up studies (historical cohort studies). A population of occupationally-exposed persons is assembled on the basis of past records and is followed until the present to determine mortality experience. The total population is used is used as a standard to compute standardized mortality ratios (SMR) or proportional Mortality Ratios (PMR). Occupational morbidity studies are based on case reports of acute cases or previous records. Occupational health surveys of the health status of workers are undertaken by a surveillance system.

PREVENTION OF OCCUPATIONAL DISEASE

Primary prevention is to reduce exposure. Chemical hazards can be substituted, enclosed, or removed at source. Workers can be segregated from hazards or can be given personal protection. Ventilation and dilution can decrease the exposure risk. Personal hygiene prevents infectious disease. Additional measures are education, information, legislation, and monitoring for early detection. Ergonomics is making the job fit the worker such that there is no harm. A safe working environment has good lighting, appropriate temperature and humidity, acceptable levels of vibration and noise, and firm non-slippery ground.

Secondary prevention is reducing the effects of the exposure by identification of the hazard, measuring it, implementing controls, evaluation, and monitoring/surveillance (physical, biological, chemical, or radiological). Control may be by engineering control, personal protection, standards, isolation, ventilation, and education.

Tertiary prevention is reducing the effects of disease (complications and disability). Workmen compensation insurance ensures health care for those injured at work, assures income replacement for those injured.

Surveillance of occupational disease consists of occupational hazard surveillance and occupational disease surveillance.

Key Words and Terms: Ergonomics, Occupational Accident, Occupational Disease, Occupational Exposure, Occupational Hazard, Occupational Health, Occupational Injury, Occupational Medicine.

NUTRITIONAL EXPOSURES

INTRODUCTION

Nutritional epidemiology studies the relation between diet and disease. Nutrition is the process by which food is ingested and utilized by the body. Food has 3 functions: provision of energy, growth and repair, and maintenance of the body in the best physiologic state by providing micro-nutrients needed in metabolic pathways. The types of foods are carbohydrates, fats, proteins, and micronutrients (vitamins and minerals). Food requirements are higher in infants and children as well as in pregnancy and lactation. Recommended daily allowances are minimum food requirements. Primary nutritional disorders may be due to deficiency (protein-energy malnutrition, vitamin deficiency, mineral deficiency) or due to excess (vitamin excess, obesity). Secondary nutritional disorders arise in disease states. They arise due to inadequate dietary intake, maldigestion, malabsorption, increased nutrient requirements, and loss of endogenous nutrients.

INCIDENCE AND PREVALENCE OF MALNUTRITION

PEM occurs in children in LDC and adults in hospital. Obesity is worldwide being more in DC and high SES. Vitamin deficiency is worldwide being more in LDC. Mineral deficiency is worldwide. Vitamin excess such as hypervitaminosis A and D are due to excessive medical intake.

DISEASES ASSOCIATED WITH MALNUTRITION

Diseases have specific nutritional risk factors: hypertension (high sodium intake), CHD (high dietary unsaturated fats, low dietary fiber), esophageal cancer (preservatives like nitrosamines, alcohol, mycotoxins, and dietary deficiency of zinc, carotenoids, retinol), stomach cancer (nitrosamines and fat), colon cancer (high protein, high fat, low fiber), gall stones (high cholesterol, high sugar, and low fiber), liver cancer (aflatoxin), pancreatitis (PEM), dental caries (prolonged contact of sugar with teeth), diabetes type 2 (high fat and low fiber), urinary calculi (high phosphate), xerophthalmia (vitamin A (carotene) deficiency), beriberi (vitamin B1/thiamine deficiency), pellagra (vitamin B3/niacin deficiency), scurvy (vitamin C/niacin deficiency), rickets (vitamin D5 deficiency), clotting failure (vitamin K deficiency), neural tube defects (folic acid deficiency in pregnancy), anemia (iron deficiency), goiter (iodine deficiency), and dental caries (fluorine deficiency).

ASSESSMENT OF NUTRITIONAL STATUS

Diet is measured as a specific food, a food group, or a nutrient (specific chemical compound in food). Dietary intake can also be measured as its effects either biochemical or anthropometric. Short term biochemical assessments are serum analysis for lipids (eg cholesterol and albumin), vitamins, and fatty acids, fecal analysis (lipids and vitamins), urine analysis (vitamins, minerals and ions, 24-hour urine nitrogen, urea, and creatinine), bile salts analysis (cholesterol). Biochemical medium or long-term measures are red blood cell analysis (vitamins, folic acid, selenium, copper and fatty acids), white blood cell analysis (vitamins, zinc, selenium, and fatty acids), hair and nail analysis (zinc, copper, selenium, and other trace elements), subcutaneous fat analysis (retinol, carotenoids, and fatty acids). Sampling bias may occur in biochemical assessments especially if the sample is after a meal. Diseases also distort interpretation of biochemical findings.

Household food intake is assessed in 4 ways: food accounting (list of all foods entering the household list of all foods entering the household) food inventory (record of all food coming into the house in addition to inventory taking at the start and end of the study periods), household record (recording all food, raw or cooked, available for consumption and estimated in household measures taking care to subtract food eaten by visitors or lost to waste), and list recall (a questionnaire of the amount and cost of food obtained for household use). Individual intake is assessed by food frequency questionnaires, dietary history obtained by interview, 24-hour recall of types of food and portions, diet history, and diet record/food record/food diary.

Indices for anthropometric assessment are defined for children (weight for age, height for age, weight for height, mid-arm circumference, and skin-fold thickness) and adults (Weight as a percentage of expected body weight and the body mass index are used to assess adult nutritional status). The body mass index (the Quetelet index) is computed as BMI = weight/height² with weight in kilograms and height in centimeters. The body mass index (BMI) is an objective measure of obesity: BMI 19-25 is considered normal range. Overweight is 26-29. Obesity is 30-39. Severe or morbid obesity is 40 and above. Obesity is controlled by decreasing food intake, exercise to increase energy expenditure, appetite suppressants (limited value), thyroxine therapy, jaw wiring, and surgical operations to reduce stomach size. The body mass index (BMI) is an objective measure of obesity: BMI 19-25 is considered normal range. Overweight is 26-29. Obesity is 30-39. Severe or morbid obesity is 40 and above. Obesity is controlled by decreasing food intake, exercise to increase energy expenditure, appetite suppressants (limited value), thyroxine therapy, jaw wiring, and surgical operations to reduce stomach size. Weight and height may be affected by genetic factors, nutritional status, disease especially infections, age, social and psychological stress, and measurement error.

EPIDEMIOLOGICAL STUDIES OF NUTRITIONAL EXPOSURES

Dietary habits, anthropometry, and biological assays can be used both as exposure or outcome variables depending on the hypotheses of study. Knowledge about and attitudes to food are used as exposure measures. Morbidity and mortality are used as outcome measures. Epidemiological studies can be observational (ecologic, cross sectional, case control, and cohort) or experimental (community intervention or random controlled clinical trials). Food intake and its effects are confoundable by a large number of social (e.g gender, ethnicity, social class or occupation, residence, marital status, and size/type of household) and psychological variables (knowledge, beliefs, attitudes, norms, values, roles, social pressures, and behavior). All nutritional studies share the problem of imprecise and nonspecific measurement of food intake.

Key Words and Terms: Adolescent Nutrition, Anthropometry, Avitaminosis, Body Mass Index, Cephalometry, Child Nutrition, Craniometry, Crown-Rump Length, Dietary Supplement, Food Frequency, Food Labeling, Hypervitaminosis, Infant Nutrition, Malnutrition, Nutritional Assessment, Nutritional Disease, Nutritional Disorders, Nutritional Requirements, Nutritional Status, Nutritional Surveys, Nutritional Value, PEM.

RADIATION EXPOSURE

OVER-VIEW

Radiation is used medically in diagnostic procedures (x-rays, radioisotopes) and treatment of malignancies. It also has military and industrial uses. Exposure to radiation is a cause of disease.

RADIATIONS: TYPES, SOURCES, AND MEASUREMENT

Radiations may be ionizing photons (gamma and x-rays), ionizing particles (alpha and beta), non-ionizing (UV light, visible light, and infrared light), low frequency electromagnetic fields from power lines, or ultra sound. The Gray is a measure of the amount of the absorbed radiation dose. The Sievert measures the effective dose equivalent by taking into account the ionizing power of the radiation. The relative biological effect (RBE) depends on linear energy transfer (LET). The roentgen equivalent man (REM) is a measure of the biological damage to tissues.

There are 2 main sources of radiation in the environment: background natural radiation (cosmic or solar from space such as UV, geological /terrestrial from the rocks, inhaled radioactive material, and the radio-active gas radon) and man -made radioactive sources (nuclear bombs, emissions from nuclear power plants, medical exposure, residential exposures to TV and appliance, and occupational exposures). UV is associated with skin cancers (basal cell carcinoma, squamous cell carcinoma, and malignant melanoma). Radon has high concentrations in houses and causes lung cancer. Skin cancer is prevented by avoiding sun exposure. Exposure to radon is prevented by filling up cracks in homes and using concrete foundations. Electromagnetic fields are suspected to cause cancer, adverse reproductive outcomes, and behavioral or neural effects. Residential exposure (from TV, video, and appliances) may lead to childhood and adult malignancy (leukemia and brain cancer). Occupational exposure may also lead to leukemia and brain cancer.

EFFECTS OF RADIATION

Ionizing radiations cause DNA damage, DNA mutations, and chromosomal aberrations. Effects on germ cells, unlike on somatic cells, can be transmitted to the next generation. The factors influencing biological effects depend on the type and energy of radiation, time of exposure, accumulated dose, and the target tissue. The bone marrow, intestine, skin, and lungs are most affected. Health effects of radiation may be acute (sunburn, photosensitivity, and the acute radiation syndrome) or chronic (cancer, infertility, teratogenesis, and dermatological). There is a disagreement about existence of a threshold.

EPIDEMIOLOGICAL STUDIES OF RADIATION:

The objective of epidemiological study is to relate exposure to health effects and to relate dose to biological effects. Leukemia risk was found raised in atomic bomb survivors, persons irradiated for ankylosing spondylitis, and women irradiated for cancer of the cervix. Thyroid cancer risk was found raised in atomic bomb survivors, children irradiated for tinea capitis, and children irradiated for thymic enlargement. Breast cancer risk was found raised in atomic bomb survivors, women irradiation for post-partum mastitis, and persons who underwent fluoroscopy for diagnosis of tuberculosis. Liver cancer risk was found raised in atomic bomb survivors, and miners exposed to radon. Multiple myeloma risk was raised in atomic bomb survivors. No new genetic diseases have been detected among those irradiated. Neither have the studies confirmed an increase in the known genetic diseases among those irradiated. This indicates that cellular repair mechanisms are able to repair radiation damage. Studies have been undertaken to establish a dose-effect relationship between risk of disease and amount of radiation exposure. Results are generally not conclusive.

PREVENTION OF RADIATION DAMAGE:

Primary prevention is to prevent or limit exposure (minimal medical or occupational exposure, use of personal monitoring by dosimeters, prevention of nuclear war and nuclear accidents, safe disposal of nuclear waste). Secondary prevention is mostly supportive: treatment of infection, replacement of bone marrow, and emergency measures during nuclear accidents (stay indoors, iodine tablets, evacuating of residents, controlling exposed food stuff, and decontaminating the environment). Tertiary prevention is by long-term follow-up for those exposed because effects may appear late. Genetic counseling may be necessary.

Key Words and Terms: Cosmic radiation, Dose-response, Ionizing radiation, Radiation accident, Radiation carcinogenesis, Radiation dose, Radiation genetics, Radiation injury, Radiation measurements, Radiation monitoring, Radiation oncology, Radiation protection, Radiation safety, Radiation teratogenesis, Radiation workers, Radiochemistry, Radiometry, Radionuclide imaging, Radiotherapy, Radiation sensitive agents, Relative biological effectiveness, Tomography, Ultrasonography, Whole body irradiation

OTHER EXPOSURES

BIOLOGICAL MARKERS

Molecular epidemiology is use of biological markers (cellular, biochemical, molecular, genetic, immunologic, or physiological) to study disease-exposure relations. Both exposure and outcome biomarkers are used. A marker is selected on the basis of biologic relevance, pharmacokinetics, temporal relevance, background variability, confounding, reproducibility, specificity, sensitivity, and predictive value. Markers are validated as correct measures of exposure, disease, and susceptibility by use of dose response relations, inter-personal or intra-personal variation, and correlation with clinical status or with other biomarkers. Cardiovascular markers are of three main classes: lipid-related (total cholesterol, triglycerides, low density lipoproproteins, high density lipoproteins, Apo B and Apo A1), markers of thrombosis (factor VIII, plasma fibrinogen, platelet counts, and platelet aggregation) and markers of disease outcome (various enzymes in myocardial infarction). Markers in genetic diseases are metabolites such as PKU or antigen systems such as HLA. Biomarkers are used in carcinogenesis to measure doses of potential carcinogens (eg DDT, PCB, aflatoxin), assay of early biological effects (chromosomal aberrations), and screen for mutagens (Ames test). Biomarkers in infectious disease are serum antibodies.

GENETIC EXPOSURES

Genetic epidemiology investigates the role of genetic factors and their interaction with environmental factors in disease etiology. Chronic diseases with a genetic component occur in 5-10% of adults. About 1 in 50 of newborns has a congenital anomaly that may have a genetic basis. Anomalies may be of the DNA molecule (deletion of a gene, point mutation involving a single base change, insertion or deletion of nucleotides, and fusion of genes) or of the chromosome (abnormal number, translocation, deletion, and insertion of a chromosome). Alleles may be homozygous or heterozygous. The genes may be dominant or recessive. The pair of alleles can be both dominant (called co-dominance), or both recessive, or one can be dominant and the other recessive. Only one abnormal dominant allele causes disease. Both alleles must be recessive to cause disease. Dominant genes will exert their effect in both homozygous and heterozygous situations. Recessive genes exert their effect only in the homozygous situation. Genotype refers to the genetic composition inherited from parents. Gene expression is sometimes not perfect because of the phenomenon of incomplete gene penetrance. Incomplete dominance is a situation of intermediate inheritance in which both alleles express themselves in an offspring such that the phenotype is intermediate between the 2 homozygous individuals.

Chromosomal disorders can be autosomal disorders (Down's syndrome is trisomy 21, Edward's syndrome is trisomy 18, Patau's syndrome is trisomy 13), sex-linked disorders (Kilnefelter's syndrome (47, XXY), XYY male, Turner's syndrome (45,X), and 47, XXX female. The following chromosomal aberration-malignancy links have been established: Chronic granulocytic leukemia and t(9:22), Burkitt's Lymphoma and t(8:2), t(8:14), t(8;22); acute myeloblastic leukemia and t(8:21); chronic lymphocytic leukemia and trisomy 12; retinoblastoma and del (13q); Wilm's tumor and del (11p); acute lymphocytic leukemia and trisomy 21. The following genetic disorders are associated with chromosomal breakage: Fanconi's anemia, Ataxia telengiectasia, Bloom syndrome, and Xeroderma pigmentosum. The following are single gene disorders: aminoacidopathies (phenylketonuria, homcystinuria, cystinosis, and alkaptonuria), transport disorders (cystinuria, nephrogenic diabetes insipidus, and hartnup disease), storage disorders (glycogen storage disorders, sphingolipidoses, gangliosidoses, and muco-polysaccharidoses), connective tissue disorders (collagen disorders, osteogenesis imperfecta, and marfan's syndrome). Multifactorial disorders involve both a polygenic genetic factor and an environmental factor. The common multi-factorial disorders are malformations (cleft palate, cleft lip, club foot, dislocation of hip, congenital heart disease, Hirschprung's disease, and pyloric stenosis) or multifactorial diseases with genetic markers (insulin-dependent diabetes (HLA haplotypes eg B8, B15, DW3, DW4), celiac disease (HLA-A1-B8-DW3), ankylosing spondylitis (HLA-B27), peptic ulceration (blood group O), atherosclerosis (apolipoprotein A-1, low density lipoprotein receptors, apolipoprotein E).

Epidemiological studies of genetic diseases use the following designs: case control studies (most popular), cohort studies, cross sectional studies, family studies, twin studies, adoption studies, migrant studies, and affected relative study.

Primary prevention of genetic disease is by genetic counseling (discouraging consanguinity, pre-marital/pre-pregnancy risk assessment based on family history and diagnosis of disease in family members), screening (phenylketonuria, hypothyroidism, cystic fibrosis, sickle cell disease, Tay-Sachs disease, adult-onset polycystic kidney disease, multiple endocrine adenomatosis, familial polyposis coli). Secondary prevention is by surgical correction, replacement therapy (eg insulin for diabetes mellitus), amelioration therapy (restricted diet in phenylketonuria), preventive therapy (remove polyposis coli), and gene therapy). Tertiary prevention is supportive.

PHARMACEUTICAL AGENTS

Adverse drug effects: As more drugs are available for use, toxicity incidents also increase. Any drug can cause ARD. The commonest ADRs are due to: anti-HTsives, anti-coagulants, cytotoxics, corticosteroids, and digoxin. Risk of ADR: The young children and the elderly are at higher risk for ADR. Women are at higher risk than men. Adverse drug reactions (ADR) are classified as type A and type B. Type A reactions are due to the known pharmacological effects of the drug. They are dose dependent, predictable, and not so severe). Type B reactions are rare idiosyncratic reactions of the drug. They are non-dose dependent, unpredictable and have more mortality. In the UK, 5% of all hospital admissions are due to ADR. 1 in 10 admitted for other reasons develop ADR. 1 in 1000 of hospital deaths is due to ADR. Primary prevention of ADR is by control of prescription, knowing allergies avoiding polypharmacy, and rational drug use. Secondary prevention of ADR is by stopping the drug, using an antidote, monitoring for further side-effects. Post-marketing surveillance of drugs is necessary to pick up more ADRs.

Drug interactions: 10-20% of all ADR are due to drug interactions. Primary prevention is by recording of all drugs the patient is taking and making sure no drugs known to interact are given. Secondary prevention is by stopping / substituting one of the pair of interacting drugs. Tertiary prevention is by treating any complications.

Drug poisoning: Drug Poisoning: can be accidental or deliberate and causes 10% of acute hospital admissions. The common causes are CO 23%, barbiturates 21%, analgesics 17%, anti-depressants 7%, tranquilizers 7%, and Others 25% (household solvents, corrosives, and caustics are common causes of child poisoning). Primary prevention of drug poisoning is to keep drugs out of reach of children and the elderly, use of child-resistant or child-proof container caps, education, and information through the mass media. Secondary prevention is by removing the poison (gastric lavage, induced emesis, adsorbents), anti-dotes, and elimination (forced diuresis, hemoperfusion), life support (cardio-vascular & respiratory). Tertiary prevention is preventing complications by skin care, bladder care, and using anti-convulsants.

Key Words and Terms: Alleles, Chromosome Mapping, Cloning, Conjugation, Gene Expression, Gene Frequency, Gene Library, Genetic Algorithm, Genetic Code, Genetic Counseling, Genetic Cross-Over, Genetic Engineering, Genetic Markers, Genetic Models, Genetic Predisposition, Genetic Regulation, Genetic Screening, Genetic Transcription, Genetic Vectors, Genetics Dictionary, Genome Library, Heterozygous, Homozygous, Statistical Models In Genetics, Mutation, Non-Disjunction, Operator Regions, Pedigree, Penetrance, Polymorphism, Population Genetics, Promotor Region, Recombination, Regulatory Sequences, Repressor Proteins, Suppressor Region, Terminator Region, Transduction, Translation, Adverse Drug Reactions, Drug Abuse, Drug Approval, Drug Chemistry, Drug Control, Drug Costs, Drug Design, Drug Incompatibility, Drug Industry, Drug Interactions, Drug Labeling, Drug Poisoning, Medication Abuse, Medication Errors, Narcotic Control, Pharmaceutical Preparation.