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PubMed2005

Pulmonary embolism: impact of right ventricular dysfunction.

PURPOSE OF REVIEW: The appropriate treatment of patients with acute pulmonary embolism who present with right ventricular dysfunction but normal arterial blood pressure, and particularly the potential benefits of thrombolytic treatment in this setting, continue to be highly controversial. In the past year, several well designed studies improved our understanding of subclinical right ventricular dysfunction in pulmonary embolism, and emerging risk stratification algorithms now appear to identify high-risk patients reliably. RECENT FINDINGS: A meta-analysis confirmed that echocardiographically diagnosed right ventricular dysfunction is an independent predictor of early mortality in normotensive patients with pulmonary embolism. Retrospective studies suggest that similar information can also be obtained by multidetector-row chest computed tomography. Recent data indicate that biomarker (particularly troponin) testing followed by echocardiographic imaging of the right ventricle is an efficient and reliable strategy both for excluding (ruling out) and for predicting (ruling in) a poor outcome in patients with pulmonary embolism. SUMMARY: Novel risk stratification algorithms may help identify possible candidates for early thrombolytic treatment in pulmonary embolism and thus provide the background for a large international multicenter study that will hopefully resolve the 30-year-old debate on the benefits of thrombolysis in normotensive patients with pulmonary embolism and right ventricular dysfunction.

Algorithms↗
PubMed2001

Evidence for DNA damage in patients with coronary artery disease.

According to the "monoclonal hypothesis" of atherosclerosis, several studies suggest that cancer and atherosclerosis may have several fundamental biological mechanisms in common. Therefore, an increase in the mutation rate may be involved in the pathogenesis of atherosclerotic plaques. The aim of the study was to verify the presence of chromosomal damage in peripheral blood lymphocytes in patients with coronary artery disease by using micronucleus (MN) test, a reliable biomarker in genetic and cancer risk assessment. Subjects included 53 patients with documented coronary ischemic heart disease (group I); 10 patients with valvular heart disease in absence of atherosclerotic lesions of the coronary arteries (group II) and 16 healthy subjects, age- and sex-matched (group III) were studied as controls. For each subject, two separate cultures were performed and 1000 binucleated cells were scored for the evaluation of MN frequency. The mean (+/-S.E.M.) of MN frequency were 11.9+/-1.7, 5.9+/-1.2 and 3.6+/-0.7 in groups I, II and III, respectively. The MN frequency of group I was significantly higher than that of group III (P=0.02). In group I, MN frequency increased with the number of affected vessels (6.3+/-0.7, 13.9+/-1.6, 14.9+/-5.3 for one-, two-, and three-vessel disease, respectively). Scheffe's test showed that MN frequency was significantly higher in two-vessel compared with one-vessel disease (P=0.0077). Moreover, a positive relationship was found between MN levels and the severity of the disease, calculated by the Duke scoring system (R=0.28, P=0.032), as well as the systolic blood pressure (R=0.34, P=0.009). These results suggest that coronary artery disease in humans is a condition characterized by an increase of DNA damage, positively correlated with the severity of the atherosclerotic disease.

Adult↗
PubMed1999

Loss of heterozygosity in epithelial cells obtained by bronchial brushing: clinical utility in lung cancer.

To determine whether loss of heterozygosity (LOH) could be a useful diagnostic test for lung cancer, we evaluated LOH in cells obtained from bronchial brushings. Cells from radiographically normal and abnormal lungs were obtained from 55 patients undergoing diagnostic bronchoscopy. Among 38 patients with lung cancer, LOH was present in at least one chromosomal locus in 79%, whereas cytology was positive for malignant cells in 37%. LOH was not restricted to the airway containing the tumor; fifty-three percent of the cancer patients had LOH in the contralateral lung, as did 59% of patients without lung cancer. There was an association between the extent of LOH and proximity to the cancer. The LOH score, which combined measures of fractional allelic loss and percentage of cells with allelic loss, was greater in subjects with positive cytology and on the side of the tumor. A LOH score >10 was positive in 58% of tumor-bearing lungs, in 13% of the contralateral lungs in cancer patients, and in no patients without cancer. Our results suggest that extensive and widespread allelic loss, as indicated by a high LOH score, may be diagnostic of lung cancer. Additional studies will be needed to clarify the clinical potential of using bronchial epithelial cell LOH as a biomarker and diagnostic test for lung cancer.

Adult↗
PubMed2001

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

Dementia↗
PubMed2005

Gene polymorphisms and serological markers of patients with active Crohn's disease in a clinical trial of antisense to ICAM-1.

Serological profiles for anti-Saccharomyces cerevisiae antibodies (ASCA)/ perinuclear antineutrophil cytoplasmic antibodies (pANCA) and gene polymorphisms in tumour necrosis factor (TNF)-alpha and intercellular adhesion molecule-1 (ICAM-1) are associated with occurrence and/or outcome in Crohn's disease. The aim of the study was to characterize the ASCA/pANCA profile, soluble ICAM-1 expression and single nucleotide gene polymorphisms (SNPs) in TNF-alpha and ICAM-1 genes. Crohn's patients with moderate disease activity were enrolled in a clinical trial of Alicaforsen (ISIS 2302). Peripheral blood samples were collected prospectively for serum studies and for potential analysis of gene polymorphisms. A multivariate analysis was performed to compare treatment effect with the biomarkers studied. Serological testing for ASCA/pANCA was obtained for 257 patients at baseline: 37% were ASCA(+)/pANCA(-) (Crohn's pattern), 9% had both markers, 15% were ASCA(-)/pANCA(+) and 39% had neither marker. When the data were analysed by multiple regression analysis, a trend was found within the Alicaforsen-treated groups for greater rates of remission in the ASCA(+)/pANCA(-) subgroup versus all other serological profiles (25 versus 14%, P = 0.068), but not versus the placebo remission rate (18.8%). Gene polymorphisms were assessed in 64 patients, 21 from the placebo group. ICAM-1 assessment revealed no over-representation. However, three unique TNF-alpha SNPs were identified that correlated significantly with remission; sites 290 (P = 0.0253), -2735 (P = 0.0317) and -3090 (P = 0.0067). Although the overall clinical trial was negative, we have identified a trend towards clinical remission with Alicaforsen therapy in a subgroup of patients with Crohn's disease expressing ASCA(+)/pANCA(-). Furthermore, we have identified three TNF-alpha SNPs that may also predict a positive therapeutic outcome.

Adolescent↗
PubMed2004

[Extra-cardiac chest pain].

In patients with an acute chest pain syndrome the primary requirement is to diagnose or exclude acute myocardial ischemia or myocardial infarction. However, only 30% of patients admitted and evaluated for chest pain ultimately reveal the diagnosis of acute coronary syndrome.Traditionally, the initial evaluation of patients presenting with chest discomfort or pain to an emergency department or any general practice involves the triad of history, physical examination, and ECG and chest film evaluation. With the diagnostic routine of bedside enzymatic tests for cardiac biomarkers, it has become easier to identify acute coronary syndromes, but at the same time more compelling to pinpoint other differential diagnoses, once coronary syndromes are excluded. When a cardiac origin of any non-suggestive chest pain syndrome has been excluded, a broad spectrum of other causes for noncardiac chest pain needs to be evaluated. Potential underlying disorders are listed in this overview and grouped according to pathoanatomic origin into aortic, respiratory, and gastroesophageal disorders, musculoskeletal pathology, and somatization disorders. This article reviews both symptoms and diagnostic pathways in patients with noncardiac chest pain, and eventually offers a rational strategy for an efficacious workup of a wide spectrum of important differential diagnoses.

Aortic Diseases↗
PubMed1995

Opportunities for the development and use of biomarkers.

Limitations in understanding the relationship between occupational and environmental exposures and disease present opportunities for using biological markers to fill gaps in knowledge. Three situations can be identified that could foster the development and use of biomarkers, where epidemiological evidence is (1) definitive, (2) equivocal, and (3) lacking. When there is clear epidemiological evidence of disease risk given an exposure, biomarkers could be used to identify high- and low-risk subsets of a cohort that might benefit from differential practices such as counseling about job risks, varying frequency and intensity of medical surveillance, and using protective equipment. Biomarkers could also be used to test the effectiveness of environmental controls. Assessment of blood lead in bridge workers and purified protein derivative (PPD) testing in health care workers illustrates biomarkers that have been used to evaluate control efforts. When epidemiological evidence is equivocal, a broad and consistent database on intermediate biomarkers in the path between exposure and disease could provide a compelling case as to whether a substance should be treated as hazardous. The case of ethylene oxide illustrates this situation: the epidemiological evidence of risk of lymphohematopoietic cancer is equivocal but there is an informative database on genetic and cytogenetic changes in various species consistent with carcinogenicity. Biomarker data also can be used to assist in the interpretation of inconclusive epidemiological information as is illustrated in the case of styrene where markers provide a mechanistic rationale for the epidemiologic findings. When there is little or no epidemiological evidence of risk in an exposure situation, such as around hazardous waste operations or with new technologies, biological markers can serve as early warning indicators of exposure or risk. In such cases it is important to have an underlying biological theory and an appropriate epidemiological study design if the principal results are to be of value in indicating risk and preventing disease.

Biomarkers↗
PubMed2005

Health status of Mya arenaria bivalves collected from contaminated sites in Canada (Saguenay Fjord) and Denmark (Odense Fjord) during their reproductive period.

The purpose of this study was to examine the health status and gametogenetic activity in Mya arenaria clams collected at various sites in the St. Lawrence Estuary (Quebec, Canada) and in the Odense Fjord (Denmark). Clam soft tissues were analyzed for metals/metalloids and organotin compounds to confirm their exposure to these contaminants. Their health status was assessed by a test battery of biomarkers designed to measure the early biological effects of contaminants, which include expression of defence mechanisms such as xenobiotic conjugation (glutathione S-transferase), expression of stress proteins (i.e., heme oxygenase and metallothioneins), changes in gametogenetic activity, and individual morphometric characteristics. Clam tissues were also examined for the presence of oxidative damage to lipids, formation of DNA strand breaks, and alterations in heme metabolism. The results showed that clams sampled from sites with either ferry activity or intensive boat traffic in marinas were contaminated by metals/metalloids such as Ag, Al, As, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sn, V, and Zn. The clams also contained relatively high amounts of tributyltin (TBT) in their tissues (in the ng TBT/g range for both areas), with digestive glands containing more organotins than did gonadal tissues. Moreover, clams collected from TBT-contaminated sites had higher amounts of tin-heme adducts and lower total heme in their digestive glands. Condition factor, age distribution, and sex ratio were significantly altered in clams from impacted sites in the Saguenay Fjord and accompanied by an increased male/female sex ratio. Gametogenetic activity was also negatively affected, as revealed by reductions in gonadosomatic index, maturation index, aspartate transcarbamylase activity, and vitellogenin-like proteins. The Saguenay Fjord clams displayed a complex pattern of stress responses and damage such as increased heme oxygenase activity, phase 2 conjugation enzyme activity, lipid peroxidation, and altered DNA strand breaks. The integration of biomarker response data into a biomarker index at the whole-individual level (morphometric characteristics) and for various organs (gill, digestive gland, and gonad) revealed that, relative to the control site, morphological characteristics and gonadal activity were most affected at the most contaminated site, while the effects were more pronounced in the digestive gland and gill at moderately impacted sites. We conclude that the health status of M. arenaria clams at these contaminated sites is compromised, with obvious disruption of reproductive activity.

Animals↗
PubMed2006

Histologic grading of noninvasive papillary urothelial neoplasms.

OBJECTIVES: In 1998, a revised system of classifying noninvasive papillary urothelial neoplasms of the urinary bladder was proposed and subsequently formally adopted by the World Health Organization (WHO). The introduction of this new system was justified as being potentially superior on a number of levels to the 1973 WHO classification system that it replaced. Specifically, a new category of neoplasms, designated papillary urothelial neoplasm of low malignant potential (PUNLMP), was considered advantageous for several reasons. The new system was expected to gain widespread acceptance, improve reproducibility of diagnoses among pathologists, and enhance the correlation between urine cytology and tumor histology. We examine the history of the changes in terminology for these lesions, the relative merits of PUNLMP terminology, the extent to which the expectations accompanying the new grading system have been met, and the extent to which the new system has enhanced the management of patients with noninvasive papillary urothelial neoplasms of the bladder. METHODS: A PubMed literature search after the introduction of this new classification was performed and relevant papers reviewed. RESULTS AND CONCLUSIONS: The 2004 WHO classification is a positive initiative in attempting to standardize urothelial tumor grading by expanding and clearly defining the morphologic characteristics of noninvasive papillary urothelial neoplasms. The new terminology used in this system is of questionable validity and utility. Full-genome searches for prognostic and predictive molecular gene expression signatures, GeneChip technology and proteomics techniques, and several new biomarkers and molecular tests may be useful in future grading schemes after their clinical utility is better established.

Carcinoma, Transitional Cell↗
PubMed2026

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Studying brain gene expression in Alzheimer's Disease (AD) remains difficult as postmortem brain is difficult to access, cannot be used to guide donor treatment, may be confounded by environmental factors before and after death, and is difficult to link to early AD states or disease progression. To circumvent these limitations, several studies have tested blood transcriptome biomarkers for AD. However, gene-expression levels in the blood have limited correlation with those in the brain. To evaluate the potential of monitoring Alzheimer's progression with peripheral data, we used transcriptome-imputation to identify brain-region-specific AD-associated gene-expression differences in cohorts with blood-based transcriptome data. This approach provides a high-resolution image of AD-associated molecular differences in the brains of individuals actively living with disease. We analyzed eight AD studies (777 AD cases, 779 cognitively unimpaired controls), imputing transcriptomes in 10 brain regions via the Brain Gene Expression and Network Imputation Engine (BrainGENIE). Hundreds of differentially expressed genes (DEGs) associated with AD were identified in nine brain regions, with anterior cingulate cortex and amygdala showing the most differential expression. AD-associated genes were enriched in pathways such as proteostasis, mitochondrial dysfunction, and immune activation. We observed significant yet moderate concordance between imputed AD-associated changes and those directly measured in the dorsolateral prefrontal cortex and cerebellum. These transcriptomic changes can guide future in vitro studies focused on pathogenesis or be targets of novel therapeutic development. In conclusion, we demonstrated the scope and utility of brain expression imputation from the peripheral transcriptome, laying the groundwork for biomarker discovery and prospective AD studies.

Alzheimer Disease↗
PubMedDate not supplied

The prostate, lung, colon, and ovarian (PLCO) cancer screening trial: Status and promise.

The Prostate, Lung, Cancer, and Ovarian Cancer Screening Trial is a randomized, multicenter, study evaluating whether screening for prostate, lung, colon, and ovarian cancer will reduce cancer-specific mortality. More than 155,000 participants have been identified and will be monitored through 2015. A biorepository of screened individuals and control participants has been created. Together, the data derived from the intervention and control arms and material in the biorepository provide a valuable resource to allow identification and testing of novel biomarkers for human disease.

Aged↗
PubMed2003

Alkyl amides and nitriles as novel tracers for biomass burning.

The occurrence of n-alkanoic acids, amides, and nitriles in samples of aerosol particulate matter from Kuala Lumpur and Santiago suggests that emissions from cooking and biomass burning are the primary sources of these organic markers in the atmosphere. It is proposed that fatty acids react with ammonia during biomass burning or combustion to produce amides and nitriles, which can be applied as useful biomarker tracers. To test this hypothesis, nonadecanoic acid and hexadecanamide were used as reactants in hydrous pyrolysis experiments. These experiments produced amides and nitriles and indicated that ammonia is an essential agent in their formation. Thus amides and nitriles are of utility as indicators for input from combustion and biomass burning in the ambient atmosphere.

Air Pollutants↗
PubMed2003

What do human micronuclei contain?

As micronuclei (MN) derive from chromosomal fragments and whole chromosomes lagging behind in anaphase, the MN assay can be used to show both clastogenic and aneugenic effects. The distinction between these phenomena is important, since the exposure studied often induces only one type of MN. This particularly concerns the use of MN as a biomarker of genotoxic exposure and effects, where differences in MN frequencies between exposed subjects and referents are expected to be small. A specific analysis of the induced type of MN may considerably improve the sensitivity of detecting the exposure effect. MN harbouring chromosomes can be distinguished from those harbouring acentric fragments by the presence of a centromere. The proportion of centromere-positive MN in human lymphocytes increases with age, which primarily reflects an age-dependent micronucleation of the X and Y chromosomes. The X chromosome especially tends to lag behind in female lymphocyte anaphase, being micronucleated more efficiently than autosomes. There is some evidence for an enhanced prevalence of fragments from chromosome 9 in spontaneous human lymphocyte MN and from chromosomes 1, 9 or 16 in MN induced in vitro by some clastogens; the breakage appears to occur in the heterochromatic block of these chromosomes. Although there are indications that centromere identification can improve the detection of clastogenic effects in humans in vivo, smokers have not shown an increase in centromere-negative MN in their cultured lymphocytes, although smoking is known to produce chromosomal aberrations. This may suggest that fragment-containing MN and chromosomal aberrations cover partly different phenomena. Understanding the mechanistic origin and contents of MN is essential for the proper use of this cytogenetic end-point in biomarker studies, genotoxicity testing and risk assessment.

Chromosomes, Human↗
PubMed2003

Alcohol and cardiovascular disease--more than one paradox to consider. Average volume of alcohol consumption, patterns of drinking and risk of coronary heart disease--a review.

The effect of average volume of alcohol on coronary heart disease (CHD) is J-shaped in established market economies. Light to moderate drinkers have less risk than abstainers, with heavy drinkers displaying the highest level of risk. This relationship between average volume of alcohol consumption and CHD is modified by different patterns of drinking. Heavy drinking occasions as well as drinking outside meals are related to increased CHD risk, independently of volume of drinking. Beverage type does not seem to have much impact, even though there are some indications that wine is more protective than other forms of alcohol. Physiological mechanisms have been identified to explain this complex relationship between alcohol and CHD. Since patterns of drinking are important in determining CHD risk, they should be included in future epidemiologic studies, together with biomarkers further to test hypotheses about pathways.

Alcohol Drinking↗
PubMed1998

Integrated defense system overlaps as a disease model: with examples for multiple chemical sensitivity.

The central nervous, immune, and endocrine systems communicate through multiple common messengers. Over evolutionary time, what may be termed integrated defense system(s) (IDS) have developed to coordinate these communications for specific contexts; these include the stress response, acute-phase response, nonspecific immune response, immune response to antigen, kindling, tolerance, time-dependent sensitization, neurogenic switching, and traumatic dissociation (TD). These IDSs are described and their overlap is examined. Three models of disease production are generated: damage, in which IDSs function incorrectly; inadequate/inappropriate, in which IDS response is outstripped by a changing context; and evolving/learning, in which the IDS learned response to a context is deemed pathologic. Mechanisms of multiple chemical sensitivity (MCS) are developed from several IDS disease models. Model 1A is pesticide damage to the central nervous system, overlapping with body chemical burdens, TD, and chronic zinc deficiency; model 1B is benzene disruption of interleukin-1, overlapping with childhood developmental windows and hapten-antigenic spreading; and model 1C is autoimmunity to immunoglobulin-G (IgG), overlapping with spreading to other IgG-inducers, sudden spreading of inciters, and food-contaminating chemicals. Model 2A is chemical and stress overload, including comparison with the susceptibility/sensitization/triggering/spreading model; model 2B is genetic mercury allergy, overlapping with: heavy metals/zinc displacement and childhood/gestational mercury exposures; and model 3 is MCS as evolution and learning. Remarks are offered on current MCS research. Problems with clinical measurement are suggested on the basis of IDS models. Large-sample patient self-report epidemiology is described as an alternative or addition to clinical biomarker and animal testing.

Acute-Phase Reaction↗
PubMed2005

Unexpectedly high prevalence of alcohol use among pregnant Swedish women: failed detection by antenatal care and simple tools that improve detection.

OBJECTIVE: We examined the use of alcohol during early pregnancy in urban Swedish women, the ability of Swedish antenatal care to identify alcohol-related risk pregnancies and the utility of some potential tools for improving its performance. METHOD: Women attending regular antenatal care were randomized to regular assessment only (control, n = 156) or intensified screening (intervention, n = 147). In the intervention group, alcohol use was determined using the Timeline Followback (TLFB) interview, alcohol use habits with the Alcohol Use Disorder Inventory Test (AUDIT), and biomarkers for alcohol use were analyzed. Data were typically obtained in pregnancy week 12. RESULTS: In the intervention group as a whole, average absolute alcohol consumption during the first 6 weeks of pregnancy was low but highly variable (mean [SD] = 24.9 [50.5] g/week; 4.8 [6.0] episodes for the entire 6 week period); 22 women (15%) drank at levels exceeding 70 g/week during any 2 or more weeks and/or in a heavy episodic drinking pattern, 60 g/episode, on 2 or more episodes. The AUDIT had a moderate sensitivity (54%) to identify these subjects. Biomarkers identified subjects with somatic illness rather than high alcohol consumption. In the control group, only 4 (3%) were identified as using alcohol, indicating a probable underestimation of alcohol use by regular antenatal screening procedures (p = .0001). CONCLUSIONS: An unexpected proportion of pregnant women in urban Sweden consume alcohol at levels likely to produce adverse effects. Regular antenatal care did not identify most of these risk pregnancies. The TLFB identified pregnant women with risk use of alcohol during pregnancy who were only partly identified by analyzing prepregnancy alcohol use patterns with the AUDIT. Elevated laboratory markers likely indicated somatic illness rather than harmful drinking.

Adult↗
PubMed2005

Assays for membrane tyrosine kinase receptors: methods for high-throughput screening and utility for diagnostics.

The development of novel antagonists or agonists of membrane tyrosine kinase receptors is a large focus of discovery research. This review will provide some background on membrane tyrosine kinases as well as a description of some of the better established assays used for the high-throughput screening of membrane tyrosine kinase inhibitors. Biochemical methods detailed include those using labels such as radioactivity and fluorescence (fluorescence energy transfer, fluorescence and fluorescence polarization) as well as label-free assays using luminescence. These assays are solid phase, liquid phase, as well as bead based. In addition, a discussion on which tools are available to screen for membrane tyrosine kinase receptor modulators/activators using whole-cell assays will be presented. The potential clinical need for testing receptor activation/phosphorylation as well as the possibility of using some of these tests to measure biomarkers of disease or as clinical diagnostic tools to tailor drug therapy or monitor its efficacy will also be discussed.

Animals↗
PubMed1999

Molecular and genetic damage from environmental tobacco smoke in young children.

To assess the risks of early life exposure to environmental tobacco smoke (ETS), we tested whether four biomarkers in peripheral blood were associated with home ETS exposure in Hispanic and African-American children. The biomarkers included cotinine (a metabolite of nicotine) and three indicators of molecular and genetic damage from mutagens/carcinogens, protein adducts formed by the carcinogens 4-aminobiphenyl (4-ABP) and polycyclic aromatic hydrocarbons (PAHs), and sister chromatid exchanges (SCEs). We also explored possible ethnic differences in biomarkers. The study cohort comprised 109 Hispanic and African-American preschool children (1-6 years of age). Plasma cotinine was analyzed by gas chromatography, 4-ABP-hemoglobin adducts by gas chromatography-mass spectroscopy, PAH-albumin adducts by ELISA, and SCEs by cytogenetic techniques. Data on the amount of smoking by mothers (average 10.5 cigarettes per day) and other household members and regular visitors (average 6.5 cigarettes per day) were obtained by interview-administered questionnaires. Cotinine, 4-ABP-hemoglobin adducts, and PAH-albumin were significantly higher (P < 0.05) in the ETS-exposed children compared with the unexposed. SCEs were marginally higher (P = 0.076). African-American children had higher levels of cotinine (P = 0.059) and PAH-albumin (P = 0.02) than Hispanic children, after controlling for exposure to ETS. These results indicate molecular and genetic damage in minority children with

Aminobiphenyl Compounds↗