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Effects of dietary antioxidants on the immune function of middle-aged adults.

The immune system is highly reliant on accurate cell-cell communication for optimal function, and any damage to the signalling systems involved will result in an impaired immune responsiveness. Oxidant-mediated tissue injury is a particular hazard to the immune system, since phagocytic cells produce reactive oxygen species as part of the body's defence against infection. Adequate amounts of neutralizing antioxidants are required, therefore, to prevent damage to the immune cells themselves. Many antioxidants can be obtained directly from the diet (e.g. ascorbic acid, alpha-tocopherol, carotenoids and polyphenolic flavonoids) or require micronutrients as integral components (e.g. Se in the metalloenzyme glutathione peroxidase (EC 1.11.1.9)). Numerous epidemiological studies have found strong associations between diets rich in antioxidant nutrients and a reduced incidence of cancer, and it has been suggested that a boost to the body's immune system by antioxidants might, at least in part, account for this. Although more striking effects have been observed in the elderly, there is also evidence that antioxidant nutrients can modify cell-mediated immune responses in younger individuals. Indeed, it might be essential to have an adequate intake of antioxidant nutrients from an early age in order to help prevent the development of, or at least delay the onset of, several degenerative disorders. The present paper will review the effects of specific nutrients on immune function in young to middle-aged human subjects, focusing on the antioxidant vitamins C and E, and on Se. A further review, dealing more specifically with the effects of carotenoids on human immune function, will be presented at a forthcoming meeting of the Nutrition Society.

Adult↗

High incidence of breakthrough varicella observed in healthy Japanese children immunized with live attenuated varicella vaccine (Oka strain).

In order to know the rate of occurrence of varicella among vaccinees (breakthrough varicella: BV), questionnaire postcards were sent to 593 healthy children who had received varicella vaccine (Oka strain) from March 1987 to December 1989. The questionnaire survey was repeated once a year until January 1996. The annual attack rate from the 1st to 3rd questionnaire was approximately 12%: however, from the 5th to 8th one it was 1-4%. To February 1996, the cumulative attack rate was 157/459 (34.2%). This rate was comparable to that among vaccinees who had confirmed seroconversion; namely, 51/132 (38.6%). These rates are much higher than those reported by other authors. All BV cases were clinically mild; even subjects who had received the vaccine 7 years prior to the disease showed mild symptoms. The high incidence may be partly explained by the regional epidemiology of varicella. The decrease in annual incidence with time after vaccination may be due to the following reasons: some vaccinees remained free from BV owing to reinforcement of their immunity from subclinical infection of varicella-zoster virus (VZV) and others from diminution of opportunity for exposure to VZV with increasing age. Varicella vaccine seems to be effective in modifying the symptoms of varicella, but not potent enough in protecting from VZV infection.

Adolescent↗

Bioactive substances in food: identification and potential uses.

Bioactive substances in foods can represent "extranutritional" constituents naturally present in small quantities in the food matrix, produced upon either in vivo or industrial enzymatic digestion, the latter being a result of food-processing activities. Bioactive constituents of food evoke physiological, behavioral, and immunological effects. Evidence from both epidemiological and animal studies has suggested chemopreventative roles for phytochemicals in certain forms of cancers and in the control of hyperlipidemia. Secondary products of plant metabolism can modulate xenobiotic metabolizing and cholesterol synthetic enzymes. Unique physicochemical properties of food-derived peptides with characteristic amino acid composition and sequences have been reported to influence intestinal transit, modify nutrient absorption and excretion, and exhibit immunostimulating and antihypertensive activity. Biologically active peptides derived from casein, fish muscle, and plant protein hydrolysates have been isolated, purified, and identified in peptide sequence studies. Therapeutic proteins (e.g., specific antibodies) derived from animal products such as milk may offer the potential for developing specialized food products with prophylactic as well as nutritive quality. This paper discusses the physicochemical mechanism of action of specific bioactive substances naturally present in or derived from foods. The biotechnologies employed to develop these products and the issues concerning acceptance by consumer and regulatory bodies are also addressed.

Animals↗

[Principles and definitions in epidemiology (author's transl)].

When medical research became concerned with the aetiology of chronic diseases, it also became necessary to adapt the principles enounced by Koch for the study of acute infectious diseases and this was expressed most satisfactorily by Evans. These changes entailed the profusion of new definitions of epidemiology which were recently reviewed by Evans and led him to propose a new one--the 24th. One important characteristic of epidemiology, however, does not appear clearly in these various definitions, namely that it is a branch of medicine. In short, it could be defined as the medical science of human groups. The authors show how the work of the epidemiologist parallels that of the medical practitioner facing a patient. The observation of the distribution of the disease within the population, referred to as descriptive epidemiology corresponds to the clinical examination and the enumeration of symptoms in the individual. The clinical interpretation of the symptoms and reasoning leading to a diagnosis is paralleled by the work of the "analytical" epidemiologist trying to discover the aetiological factors of the disease. The clinician finally takes action and administers treatment, while the findings of the epidemiologist find their application in Public Health preventive action. The authors conclude by proposing a modified version of Evans' definition of epidemiology; it reads: "Epidemiology is the quantitative study of physiological, prepathological and pathological conditions and processes in human populations, in relation to natural or man-made environmental factors which account for or favour their inception, development or disappearance. Its purpose is to prevent health disorders, to reduce their incidence or to lessen their ill effects. Epidemiology uses the resources of all medical sciences, plus all those--including statistics--imposed by its specific subject. It is the medical science of human groups. It completes and expands traditional medicine dealing with individuals".

Epidemiologic Methods↗

Translating evidence-based information into effective risk communication: current challenges and opportunities.

Recent medical advances and the easy availability of evidence-based information at the point of care are believed to provide physicians with improved tools for risk communication. However, evidence indicates that physicians still display marked variability in ordering tests. Factors that determine a physician's test-ordering tendencies vary by specialization, practice, geographical location, defensive practice, and tolerance of uncertainty and are also modified by patient requests. Understanding of statistical terms on the part of both physicians and patients remains limited. Physicians may display limited ability to assess pretest and posttest probabilities, especially in low- and intermediate-risk patients, even after attending short courses in epidemiology, or may find the process impractical. Presentation of diagnostic-test results in a natural-frequency format might improve understanding. Both physicians and patients have difficulty grasping the term "number needed to treat" compared with "relative risk reduction" when comparing therapeutic options. Other patient-related factors that limit understanding include low literacy, individual risk tolerance, and framing patterns of the problem (potential gains vs losses). Despite numerous available modalities (quantitative and qualitative) of risk communication, consensus over the advantage of any single modality in translating evidence into risk communication is limited. It is essential that physicians remain patient-centered, generate trust, and build a partnership with the patient to achieve consensus for medical decision-making. Future studies are indicated to assess the effectiveness of novel risk-communication modalities based on patients' and physicians' characteristics and identify appropriate modality of translating evidence (quantitative or qualitative information).

Communication↗

[Evaluation of the effects of occupational noxae on the cardiovascular system].

BACKGROUND: Working conditions and the environment may contribute to the multi-factorial aetiology of cardiovascular disease. OBJECTIVES: To provide a critical assessment of epidemiological and clinical methods and tools for evaluating the effects of occupational pathogenic noxae on the cardiovascular system. METHODS: A review was made of epidemiological and clinical studies published in the main scientific journals of occupational medicine and cardiology, in the period 1980-2003. Data sources were electronic medical data bases and conference proceedings. RESULTS AND CONCLUSION: Collecting case histories by means of free or questionnaire-structured interviews, observing specific physical signs, detecting changes in blood chemistry parameters and identifying morphological or functional abnormalities in the heart and vessels are all useful approaches. Some blood chemistry parameters that may be modified by occupational exposure or by particular conditions arising from work organization are cholesterol, triglycerides, apolipoproteins A and B, platelets, fibrinogen, factor VIIc, fibrinolysis products, plasminogen tissue activating factor, complement and glycated hemoglobin. They can all be measured easily and quickly and provide an estimate of the risk of cardiovascular disease. As high blood pressure is closely correlated to heart disease, blood pressure levels can be monitored in a working population using a standard mercury sphygmomanometer. Electronic measurement before and after a work shift and 24 hour Holter monitoring help reduce the "white coat effect" and provide further useful information. Occupational risk factors such as toxins (metals, solvents, pesticides), electromagnetic fields, extreme temperatures, noise, radiation and psychophysical stress can affect the cardiac neuro-autonomic balance of the exposed workers and cause cardiovascular abnormalities. These can be detected by long-term ECG monitoring, and are revealed as reduced heart rate variability and prolonged QT interval. Recently non-invasive systems have been adopted to detect cardiovascular lesions that are usually due to atherosclerosis. In occupational and environmental studies ultrasound measurement of intima-medial carotid thickness and brachial artery reactivity have been used to determine the effects of exposure to carbon disulfide and passive smoking. Occupational Medicine has yet to include the use of the very expensive electron-beam computed tomography for a rapid and non-invasive study of coronary artery disease.

Arrhythmias, Cardiac↗

Tnfa and Il-10 deficiencies have contrasting effects on lung tumor susceptibility: gender-dependent modulation of IL-10 haploinsufficiency.

Epidemiologic evidence suggests that pulmonary diseases with a prominent chronic inflammatory component elevate lung cancer risk. Genetic manipulations of mouse models of lung inflammation and tumorigenesis can be used to investigate this association. The genes encoding pro-inflammatory tumor necrosis factor-alpha (TNFalpha) and antiinflammatory IL-10 cytokines map within quantitative trait loci that regulate susceptibility to lung tumor development in mice; sensitive A/J and resistant C57BL/6J (B6) mice have different Tnfa and Il-10 alleles. Genetic ablation studies were performed to examine whether these genes would qualify as candidate tumor modifiers. Tnfa null (-/-) mice on a B6 background and B6.129 Il-10(-/-) mice were intercrossed with A/J mice and subjected to urethane carcinogenesis; lung tumor multiplicity was determined 20 weeks later. In the absence of one copy of Tnfa, tumor number. Male Il-10(+/+) mice developed more tumors than did female mice (P < 0.001), absence of one copy of Il-10 raised tumor number in female mice to that observed in +/+ males, but no change in multiplicity occurred in Il-10 hemizygous males. Thus, a deficit of pro-inflammatory TNFalpha decreased the number of tumors, whereas diminished gene copy number of anti-inflammatory IL-10 increased tumorigenesis; manifestation of an effect of Il-10 haploinsufficiency is gender dependent. These studies support a role for inflammation in lung cancer susceptibility.

Alleles↗

Why and how to control for age in occupational epidemiology.

In occupational epidemiology, the need to consider the age factor properly influences the choice of study design and analytical techniques. In most studies, age is viewed as a potential confounder. Age is strongly associated with end points of interest in occupational epidemiology (diseases, physiological characteristics, doses of xenobiotics, etc), but to measure age as a confounder it must be associated with the exposure under study. When the exposure of interest is time related-for example, duration of employment, time since first exposure, cumulative exposure-a strong intrinsic association with age can be anticipated, and age will behave as a (usually strong) confounder. When occupational exposures without a direct relation with age-for example, job, department, type of exposure-are evaluated, the degree and direction of confounding bias cannot be anticipated. Control of the confounding effect of age can be accomplished in the design phase of a study by way of randomisation, restriction, and matching. Randomisation is seldom viable in occupational settings. Restriction is rarely used in the case of age. Matching is often used in a case-control study as a method to increase the study efficiency, but it must be followed by proper matched or stratified analysis. Options for age adjustment in the analysis phase involve stratification and regression methods. In longitudinal studies the modified life table analysis is used to take into account the fact that subjects cross categories of age as the study proceeds. Stability of relative measures of effect over age strata favoured the greater use of relative risks than risk differences. In the presence of effect modification the influence of age should not be eliminated; its interaction with exposure should be explicitly considered.

Age Factors↗

Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample.

The clinical relevance of Recurrent Brief Depression (RBD) has not received sufficient attention to date and continues to represent a controversial issue. The present study was carried out in a community sample to evaluate the lifetime prevalence of RDB, the degree of comorbidity, as well as possible risk factors. Subjects from a community survey in Sardinia (Italy) were randomly selected from registers of a rural, an urban and a mining area (n=1040, 461 males, 579 females). Interviews were carried out by physicians using the Italian version of the Composite International Diagnostic Interview Simplified which had been modified for the purpose of this study. Lifetime prevalence of RBD was 7.6%; 5.8% in males, 9% in females. Subjects aged 18 to 24 years presented higher frequencies (13.8%, OR 2.2) than those aged 25 or over. Comorbidity with Major Depression was particularly frequent. RBD was furthermore associated with suicide attempts and substance abuse, thereby constituting an effective health problem. Further epidemiological and clinical studies of RBD are warranted in order to develop specific treatments and prevention strategies.

Adolescent↗

Clinical and pharmacological evaluation of a modified cefotaxime bid regimen versus traditional tid in pediatric lower respiratory tract infections.

It is generally accepted that the treatment of community-acquired pneumonia, either in adults or in pediatric patients, is mainly empirical. Thus, the treatment selection must fulfill both the epidemiological requirements, according to the most frequently described pathogens, and the pharmacological criteria to ensure adequate and prolonged drug concentrations at the infection site, to reach clinical efficacy. Cefotaxime has proven to be effective in this indication when traditionally administered three times daily and, more recently, twice daily, as a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To gain further evidence using this updated dosing schedule, 258 pediatric patients with lower respiratory tract infections were treated with cefotaxime 100 mg/kg/day, administered as a twice daily or three times daily regimen. In the cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete resolution of clinical signs and symptoms. Both drug schedules were well tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing schedules showed comparability. The serum half-life of desacetylcefotaxime was marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3 mg/kg doses, respectively). Results from this study support the use of twice-daily cefotaxime administration for the treatment of lower respiratory tract infections in pediatric patients.

Cefotaxime↗

Sleep-disordered breathing: implications in cerebrovascular disease.

Stroke and sleep-disordered breathing (SDB) are both common and are associated with significant morbidity and mortality. Several recent large epidemiologic studies have shown a strong association between these two disorders independent of known risk factors for stroke. This review will outline the scientific basis for this relationship and suggest SDB as a modifiable risk factor for stroke. Several studies have shown a characteristic circadian rhythmicity in stroke. The authors discussed the influence of normal sleep states as well as the effect of SDB on cerebral hemodynamics. The hemodynamic, metabolic, and hematologic changes during SDB in the form of decreased cerebral perfusion and increased coagulability are the possible pathogenetic mechanisms for stroke. There are accumulating lines of evidence that SDB may indeed cause diurnal hypertension. However, the increased risk of stroke in patients with SDB appears to be independent of coexisting hypertension, but the presence of hypertension would greatly increase the risk even further. Furthermore, several studies have documented high prevalence of sleep apnea in patients with transient ischemic attacks and stroke. SDB appears to contribute as a risk factor for stroke through hemodynamic and hematologic changes. Because of high prevalence of SDB in this population, patients with transient ischemic attacks and stroke should be screened for these disorders.

Cerebrovascular Disorders↗

Pravastatin. A pharmacoeconomic review of its use in primary and secondary prevention of coronary heart disease.

UNLABELLED: Coronary heart disease (CHD) is a major cause of death and illness in industrialised countries. Like other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin reduces total and low density lipoprotein (LDL)-cholesterol levels and increases high density lipoprotein (HDL)-cholesterol levels. Cholesterol modification with pravastatin in middle-aged hypercholesterolaemic men without CHD (i.e. primary prevention) was shown in the West of Scotland Coronary Prevention Study (WOSCOPS) to reduce the incidence of fatal and nonfatal coronary events. In several other large studies, pravastatin reduced the incidence of CHD events in patients with prior CHD (secondary prevention). Large, long term studies of the relationship between cholesterol modification and CHD event rate have been conducted for some, but not all, other HMG-CoA reductase inhibitors. A UK pharmacoeconomic analysis of the WOSCOPS data indicated that primary prevention with pravastatin was associated with a cost of 20,375 Pounds per year of life gained (YLG) [discounted]. Treatment of men at high risk for CHD resulted in a lower cost estimate (13,995 Pounds/YLG). A US economic analysis based on secondary prevention with pravastatin in large plaque regression studies suggested a net cost of drug therapy of $US7124 to $US12,665 per YLG. A number of projected-risk models have attempted to calculate the cost effectiveness of primary or secondary prevention with pravastatin compared with other lipid-modifying interventions. These comparisons indicated that pravastatin was economically superior to intensive lifestyle counselling without drug therapy. Pravastatin generally appeared to be less cost effective than other HMG-CoA reductase inhibitors, although the relative effectiveness of the various drugs depended on the model considered. Risk-projection economic models are subject to methodological limitations, principally the necessity of estimating clinical effectiveness from epidemiological data (often derived from the Framingham Heart Study). An increased absolute risk of CHD improves the cost effectiveness of lipid-lowering therapy. Thus, the cost per YLG of pravastatin in secondary prevention is, in general, lower than that of primary prevention, reflecting the higher absolute risk of second versus first CHD events. However, it is important to note that individual absolute risk rates may overlap between patients receiving primary and secondary prevention. Similarly, treatment of selected individual patients at high risk for CHD events is associated with a lower cost per YLG than unselected treatment. CONCLUSION: In large clinical studies, pravastatin effectively reduced the risk of primary and secondary CHD events. These benefits come at a substantial economic cost, but one that is in line with accepted costs for other medical interventions. Selective treatment of patients or populations at high risk of CHD events improves the cost effectiveness of pravastatin therapy.

Anticholesteremic Agents↗

An overview of cancer in children in the 1980s.

Multidisciplinary teams, therapeutic research, and large successful clinical trials have led to the exciting improved survival outlook in pediatric oncology. The development of sophisticated supportive care measures and the identification of significant prognostic variables within disease categories have dramatically altered the management and outcome for many children with cancer. Prolonged survival has focused attention on the quality of life and strategies to enable these children and their families to cope effectively with chronic, life-threatening illness. Research is ongoing on several fronts: to find innovative treatment approaches for children who currently have a poorer prognosis, to minimize or prevent acute and late toxicities by modifying treatment plans so less intensive treatment can be given to patients with a low risk of disease recurrence, and to increase our understanding of the epidemiology and etiology of childhood cancer. With the continued efforts of researchers in the laboratory and at the bedside, prevention of these catastrophic diseases may some day become a reality.

Acute Disease↗

DNA adduct burden and tobacco carcinogenesis.

DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevalent tobacco related cancers including cancer of the lung, head and neck, and bladder. The inducibility of DNA adducts following in vitro treatments using blood lymphocytes also appears to be a risk factor in the development of lung and head and neck cancer. Corroborative evidence pointing to the importance of DNA adducts in tobacco carcinogenesis include numerous studies showing associations of tobacco smoke exposure with the induction of DNA adducts in humans in vivo. Further effort is necessary, however, to more fully characterize the dose-response relationship between smoking and DNA adducts in exposed target and surrogate tissues. The relationship between gene polymorphisms thought to modify tobacco-related cancer risk and DNA adduct levels is complex. Results of some DNA adduct studies (both in vitro and in vivo) appear inconsistent with the epidemiologic findings. This is evident for polymorphisms involving both carcinogen metabolism (e.g. GSTP1) and DNA repair (e.g. XRCC1). Molecular studies of human tumors suggest associations of p53 mutation with DNA adducts and have revealed correlations of DNA adduct levels with somatic alterations (e.g. 3p21 LOH) that are thought to occur at the very earliest stages of tobacco carcinogenesis. More research is needed to assess the relationship between endogenous sources of DNA adducts and tobacco smoke exposure and the relative oncogenic effects of chemically stable versus unstable DNA adducts. Many potentially fruitful new avenues of cancer research are emerging that integrate DNA adduct analyses with assessments of smoking, genetics, diet and ambient air quality. These investigations aim to understand the multifactorial nature of interindividual variability in response to tobacco carcinogens. As these trends continue a variety of innovative study designs and approaches will become important in human populations.

Cell Transformation, Neoplastic↗

Neurobehavioral sequelae of fetal cocaine exposure.

The number of infants born to cocaine-using mothers has continued to rise during the past 5 years. Maternal cocaine use during pregnancy is associated with medical and life-style characteristics detrimental to fetal and infant development. Cocaine exposure has been independently linked to growth retardation and impaired fetal oxygenation even when polydrug use and other confounding factors are considered. Neurologic and neurobehavioral abnormalities noted in the immediate neonatal period have also been associated with fetal cocaine exposure. The direct and indirect toxic effects of cocaine, per se, have not yet been independently linked to specific behavioral outcomes because of small sample sizes, confounding factors, and lack of long-term follow-up. The impoverished environments and increased risk for out-of-family placement of cocaine-exposed infants are known independent correlates of negative developmental outcomes. Poor maternal nutrition, lack of prenatal care, and other health and life-style factors related to maternal cocaine use during pregnancy also appear to be factors mediating the developmental problems of cocaine-exposed infants. The cocaine-using mother often uses other drugs, particularly alcohol, independently known to be linked to growth and behavioral impairments similar to those proposed for cocaine-exposed infants. Accounting for these multiple confounding variables in studies of the specific effects of cocaine on neurobehavioral outcome may be scientifically appropriate, but in clinical practice these factors cannot be "isolated," and their statistical consideration in studies does not diminish clinical risk. Finally, currently available studies of behavioral outcome have restricted their samples to term infants. It is possible that preterm infants may be less affected by prenatal cocaine exposure because of decreased exposure. However, because epidemiologic studies suggest that prematurity is a sequelae of maternal cocaine use, restriction of samples to term or appropriately sized infants may underestimate the spectrum of morbidity associated with cocaine exposure. We believe that maternal cocaine use during pregnancy is a "marker" variable for early impairments in infant growth and behavioral functioning that have long-term implications for later developmental outcome, especially for learning disabilities and behavioral disorders. Critically assessing the independent contribution of cocaine to negative developmental outcome and determining whether early neonatal abnormalities are permanent or modifiable may allow clinical intervention and improved social policy. Assessing the independent effects of cocaine on child developmental outcome will require carefully designed, long-term, longitudinal, population-based studies with samples large enough to allow multivariate data analyses and statistical control of confounding medical and social variables.

Behavior↗

The adsorption of polyaromatic hydrocarbons on natural and chemically modified asbestos fibers.

Many reports indicate that the carcinogenic (genotoxic) potential of benzo[a]pyrene (B[a]P) may be enhanced several-fold by the promoter (epigenetic) effect of asbestos particles. This promoting effect could be related to the fact that when B[a]P is adsorbed onto the particles, there is a resulting enhanced transport and uptake of the carcinogen into microsomial membranes. These in vitro data bear relevance to the epidemiological studies which indicate an association between exposure to inhaled asbestos dusts and the high incidence of pulmonary cancers in smokers. Using HPLC, it has been observed that B[a]P has great affinity for natural asbestos fibers, and that chemical modification of natural chrysotile with POCl3 results in the complete loss of this adsorption potential of chrysotile for benzo[a]pyrene.

Adsorption↗

The CAFE computer program for nutritional analysis of the EPIC-Norfolk food frequency questionnaire and identification of extreme nutrient values.

BACKGROUND: Food frequency questionnaires (FFQs) are widely used in nutritional epidemiology but no papers detail the development of the supporting programs and nutritional databases. The principles involved in data collection, processing and treatment of the European Prospective Investigation into Cancer Study (EPIC)-Norfolk Study FFQ and development of the structure and content of the Compositional Analyses from Frequency Estimates (CAFE) program for calculating nutrient intakes are described. Extreme nutrient values and derivation of cut-points for data exclusion are also discussed. METHODS: The FFQ was sent to 25,637 participants. To exclude extreme (nonphysiological) outliers of nutrient intakes, the extreme top and bottom 0.5% of the ratio of energy intake to estimated basal metabolic rate was used. RESULTS: The CAFE computer program modifies nutrient intake according to specific fats used in food preparation and the amount of visible fat on meat. It incorporates different breakfast cereals and distinguishes between text for brands and types. After exclusion of outliers of nutrient intake some extreme values remained for energy, carbohydrate, protein, fat and alcohol, because of high reported frequencies of certain foods. CONCLUSIONS: The features of CAFE include flexible, updateable, databases and a novel method for matching text. The effect of extreme nutrient values on the accuracy of the FFQ in estimating diet in nutritional epidemiology should be investigated further.

Adult↗

Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research.

Oxidation of lipid, nucleic acids or protein has been suggested to be involved in the etiology of several chronic diseases including cancer, cardiovascular disease, cataract, age-related macular degeneration and aging in general. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of these and other chronic diseases. This review concentrates on the following antioxidant nutrients: beta-carotene and other carotenoids, vitamin E, vitamin C and selenium. The first part of the review emphasizes the utility of biological markers of exposure for these nutrients and the relationship to dietary intake data. The second part considers functional assays of oxidative stress status in humans including the strengths and limitations of various assays available for use in epidemiologic research. A wide variety of functional assays both in vivo and ex vivo, are covered, including various measures of lipid oxidation (thiobarbituric acid reactive substances, exhaled pentane/ethane, low-density lipoprotein resistance to oxidation, isoprostanes), DNA oxidation (oxidized DNA bases such as 8-OHdG, autoantibodies to oxidized DNA, modified Comet assay) and protein oxidation (protein carbonyls). Studies that have examined the effects of antioxidant nutrients on these functional markers are included for illustrative purposes. The review concludes with a discussion of methodologic issues and challenges for studies involving biomarkers of exposure to antioxidant nutrients and of oxidative stress status.

Antioxidants↗