The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV1 to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV1 and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Spirometry Reference Equations from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos).

RATIONALE: Accurate reference values for spirometry are important because the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiologic impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for others with Hispanic/Latino backgrounds. OBJECTIVES: To develop spirometry reference equations for adult Hispanic/Latino background groups in the United States. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) recruited a population-based probability sample of 16,415 Hispanics/Latinos aged 18-74 years living in the Bronx, Chicago, Miami, and San Diego. Participants self-identified as being of Puerto Rican, Cuban, Dominican, Mexican, or Central or South American background. Spirometry was performed using standardized methods with central quality control monitoring. Spirometric measures from a subset of 6,425 never-smoking participants without respiratory symptoms or disease were modeled as a function of sex, age, height, and Hispanic/Latino background to produce background-specific reference equations for the predicted value and lower limit of normal. MEASUREMENTS AND MAIN RESULTS: Dominican and Puerto Rican Americans had substantially lower predicted and lower limit of normal values for FVC and FEV1 than those in other Hispanic/Latino background groups and also than Mexican American values from NHANES III (Third National Health and Nutrition Examination Survey). CONCLUSIONS: For patients of Dominican and Puerto Rican background who present with pulmonary symptoms in clinical practice, use of background-specific spirometry reference equations may provide more appropriate predicted and lower limit of normal values, enabling more accurate diagnoses of abnormality and physiologic impairment.

A meta-analysis of genome-wide association studies of asthma in Puerto Ricans.

Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans.The only locus to achieve genome-wide significance was chromosome 17q21, as evidenced by our top single nucleotide polymorphism (SNP), rs907092 (OR 0.71, p=1.2×10-12) at IKZF3 Similar to results in non-Puerto Ricans, SNPs in genes in the same linkage disequilibrium block as IKZF3 (e.g. ZPBP2, ORMDL3 and GSDMB) were significantly associated with asthma in Puerto Ricans. With regard to results from a meta-analysis in Europeans, we replicated findings for rs2305480 at GSDMB, but not for SNPs in any other genes. On the other hand, we replicated results from a meta-analysis of North American populations for SNPs at IL1RL1, TSLP and GSDMB but not for IL33Our findings suggest that common variants on chromosome 17q21 have the greatest effects on asthma in Puerto Ricans.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Air Pollution, Cardiovascular Outcomes, and Social Disadvantage: The Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Social factors may enhance health effects of air pollution, yet empirical support is inconsistent. The interaction of social and environmental factors may only be evident with long-term exposures and outcomes that reflect long-term disease development. METHODS: We used cardiac magnetic resonance imaging data from the Multi-Ethnic Study of Atherosclerosis to assess left-ventricular mass index (LVMI) and left-ventricular ejection fraction (LVEF). We assigned residential concentrations of fine particulate matter (PM2.5), oxides of nitrogen, and nitrogen dioxide in the year 2000 to each participant in 2000 using prediction models. We examined modifying roles of four measures of adversity: race/ethnicity, racial/ethnic residential segregation, and socioeconomic status and psychosocial adversity as composite indices on the association between air pollution and LVMI or LVEF. RESULTS: Compared with whites, blacks showed a stronger adjusted association between air pollution and LVMI. For example, for each 5 µg/m greater PM2.5 level, whites showed a 1.0 g/m greater LVMI (95% confidence interval = -1.3, 3.1), while blacks showed an additional 4.0 g/m greater LVMI (95% confidence interval = 0.3, 8.2). Results were similar for oxides of nitrogen and nitrogen dioxide with regard to black race and LVMI. However, we found no evidence of a modifying role of other social factors or ethnic groups. Furthermore, we found no evidence of a modifying role for any social factors or racial/ethnic groups on the association between air pollution and LVEF. CONCLUSIONS: Our results suggest that racial group membership may modify the association between air pollution and cardiovascular disease.

Measurement of socio-economic status in families of children with cancer in Guatemala.

The prospects for survival of children in low and middle income countries are linked to their families socio-economic status (SES), of which income is only one component. Developing a comprehensive measure of SES is required. Informed by clinical experience, a 15-item instrument was designed in Guatemala to categorize SES by five levels in each item. Almost 75% of families attending the Unidad Nacional de Oncología Pediátrica were in the lowest three of six categories, providing a framework for stratified financial and nutritional support. The measure of SES offers an opportunity for examining associations with health outcomes throughout Latin America.

Treatment of childhood acute lymphoblastic leukemia in central America: a lower-middle income countries experience.

BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.

Brachial artery diameter and the right ventricle: the Multi-Ethnic Study of Atherosclerosis-right ventricle study.

BACKGROUND: Endothelial dysfunction is associated with left ventricular morphology and long-term cardiovascular outcomes. The purpose of this study was to assess the relationship between both baseline brachial artery diameter and peripheral endothelial function (assessed by brachial artery ultrasonography) and right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection fraction (RVEF). METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI and brachial artery ultrasonography on participants without clinical cardiovascular disease. Baseline brachial artery diameter and flow-mediated dilation were assessed. RESULTS: The mean age was 60.9 years, and 49.4% of subjects were men (n = 2,425). In adjusted models, larger brachial artery diameter was strongly associated with greater RV mass (ß = 0.55 g, P < .001), larger RVEDV (ß = 3.99 mL, P < .001), and decreased RVEF (ß = -0.46%, P = .03). These relationships persisted after further adjustment for the respective left ventricular parameters. Flow-mediated dilation was not associated with RV mass or RVEF and was only weakly associated with RVEDV. CONCLUSIONS: Brachial artery diameter is associated with greater RV mass and RVEDV, as well as lower RVEF. Changes in the systemic arterial circulation may have pathophysiologic links to pulmonary vascular dysfunction or abnormalities in RV perfusion.

Regional left ventricular systolic function and the right ventricle: the multi-ethnic study of atherosclerosis right ventricle study.

BACKGROUND: Dysfunction of the interventricular septum has been implicated in right ventricular (RV) failure. However, little is known about the relationship between ventricular septal and RV function in patients without clinical cardiovascular disease. We hypothesized that better septal function would be associated with higher RV ejection fraction and lower RV mass and volume by cardiac MRI. METHODS: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac MRI was performed on community-based participants without clinical cardiovascular disease. Images were analyzed by the harmonic phase method to measure peak circumferential systolic midventricular strain for each wall (anterior, lateral, inferior, and septal). Multivariable linear regression and generalized additive models were used to assess the relationship between septal strain and RV morphology. RESULTS: There were 917 participants (45.7% women) with a mean age of 65.7 years. Better septal function was associated with higher RV ejection fraction in a nonlinear fashion after adjustment for all covariates (P = .03). There appeared to be a threshold effect for the contribution of septal strain to RV systolic function, with an almost linear decrement in RV ejection fraction with septal strain from -18% to -10%. Septal function was not related to RV mass or volume. CONCLUSIONS: Interventricular septal function was linked to RV systolic function independent of other left ventricular regions, even in individuals without clinical cardiovascular disease. This finding confirms animal and human research suggesting the importance of septal function to the right ventricle and implies that changes in septal function could herald RV dysfunction. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00005487; URL: www.clinicaltrials.gov.

Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador.

Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4+/-6.4%) than those with ALL (12.5+/-1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL.

Disability and health-related Quality of Life in Long-term Survivors of Cancer in Childhood in Brazil

There is limited experience with patient-reported measurements of health status and health-related quality of life (HRQL) in survivors of cancer in childhood in low-income countries. The purposes of this study were to collect such measurements in Brazil, to test hypotheses about differences among diagnostic groups, and to compare results with those from other countries. Survivors were eligible if diagnosed with cancer in childhood, attending a long-term follow-up clinic, cancer free, literate, and at least 13 years of age. Health status measurements were collected using a Brazilian Portuguese Health Utilities Index questionnaire. Questionnaire responses were converted to scores for morbidity in individual health attributes and for overall HRQL. More than one-third of the 138 consecutive survivors who participated reported some cognitive disability or pain. Approximately one-quarter reported problems with vision, speech, or emotion. Mean HRQL was similar (P>0.05) among countries for survivors of acute lymphoblastic leukemia and Hodgkin disease. The results support the hypotheses that Brazilian survivors of cancer in childhood experience a wide range of disabilities and impaired HRQL, are similar to those in other countries, and should be assessed in long-term follow-up clinics.

Domestic returns from investment in the control of tuberculosis in other countries.

BACKGROUND: We hypothesized that investments to improve the control of tuberculosis in selected high-incidence countries would prove to be cost saving for the United States by reducing the incidence of the disease among migrants. METHODS: Using decision analysis, we estimated tuberculosis-related morbidity, mortality, and costs among legal immigrants and refugees, undocumented migrants, and temporary visitors from Mexico after their entry into the United States. We assessed the current strategy of radiographic screening of legal immigrants plus current tuberculosis-control programs alone and with the addition of either U.S.-funded expansion of the strategy of directly observed treatment, short course (DOTS), in Mexico or tuberculin skin testing to screen legal immigrants from Mexico. We also examined tuberculosis-related outcomes among migrants from Haiti and the Dominican Republic using the same three strategies. RESULTS: As compared with the current strategy, expanding the DOTS program in Mexico at a cost to the United States of 34.9 million dollars would result in 2591 fewer cases of tuberculosis in the United States, with 349 fewer deaths from the disease and net discounted savings of 108 million dollars over a 20-year period. Adding tuberculin skin testing to radiographic screening of legal immigrants from Mexico would result in 401 fewer cases of tuberculosis in the United States but would cost an additional 329 million dollars. Expansion of the DOTS program would remain cost saving even if the initial investment were doubled, if the United States paid for all antituberculosis drugs in Mexico, or if the decline in the incidence of tuberculosis in Mexico was less than projected. A 9.4 million dollars investment to expand the DOTS program in Haiti and the Dominican Republic would result in net U.S. savings of 20 million dollars over a 20-year period. CONCLUSIONS: U.S.-funded efforts to expand the DOTS program in Mexico, Haiti, and the Dominican Republic could reduce tuberculosis-related morbidity and mortality among migrants to the United States, producing net cost savings for the United States.

Translation and cultural adaptation of Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) with application to survivors of childhood cancer in Brazil

There are few publications reporting health-related quality of life (HRQL) in developing nations. Most instruments measuring HRQL have been developed in English-speaking countries. These instruments need to be culturally adapted for use in non-English-speaking countries. The HUI2 and HUI3 are generic, preference-based systems for describing health status and HRQL. Developed in Canada, the systems have been translated into more than a dozen languages and used worldwide in hundreds of studies of clinical and general populations. The Brazilian-Portuguese translation of the HUI systems was supervised by senior HUInc staff having experience with both the HUI systems and translations. The process included two independent forward translations of the multi-attribute health status classification systems and related questionnaires, consensus between translators on a forward translation, back-translation by two independent translators of the forward translation, and review of the back-translations by original developers of the HUI. The final questionnaires were tested by surveying a sample of convenience of 50 patients recruited at the Centro de Tratamento e Pesquisa-Hospital do Cancer in São Paulo, Brazil. Fifty patients were enrolled in the study. No assessor, patient or nurse or physician, reported problems answering the HUI questionnaires. No significant differences were found in mean overall HUI2 or HUI3 utility scores among types of assessors. Variability in scores are similar to those from other studies in Latin America and Canada. Test results provide preliminary evidence that the Brazilian-Portuguese translation is acceptable, understandable, reliable and valid for assessing health-status and HRQL among survivors of cancer in childhood in Brazil

Childhood cancer in Uruguay: 1992-1994. Incidence and mortality.

BACKGROUND: The referral of all children with cancer in Uruguay to a single center affords the opportunity to generate population-based incidence and mortality rates in this developing country in Latin America. PROCEDURE: All incident cases of cancer in children, 0-14 years of age, were ascertained from a combination of three sources for the period January 1992-December 1994. Diagnoses were grouped according to the International Classification of Childhood Cancer. Information on the size and age distribution of the total population was obtained from national census records. Follow-up was undertaken until December 1999 to afford a minimum interval of 5 years and the determination of mortality rates. RESULTS: The average annual incidence was 133.6 cases of cancer per million children per year and the disease distribution was similar to that in industrialized countries, with the exception of a higher rate and younger age distribution for the Hodgkin disease. The overall age-standardized mortality rate from cancer in childhood, at 6.5 per 100,000, was approximately twice that in the United States and Canada. CONCLUSIONS: Basic indicators of development suggest that Uruguay is more akin to the countries of North America and Western Europe than to those in the developing world. An opportunity has been identified to improve the outcome for children with cancer in this country.

Preliminary translation and cultural adaptation of Health Utilities Index questionnaires for application in Argentina.

Quality-of-life assessment is being used increasingly in clinical research. This is true particularly in the case of survivors of cancer in childhood, where improving survival rates have raised concern regarding the long-term effects of medical cure. Health-status assessment and quality-of-life instruments have been developed for the most part in the English language, thus necessitating their translation and cultural adaptation for use in non-English-speaking countries. Our purpose was to develop a set of Spanish-language questionnaires for application with a population of children with cancer in a tertiary-care center in Buenos Aires, Argentina. The Health Utilities Index (HUI), a conceptual framework for assessing health status, was chosen for this study. Three distinct questionnaires, based on the HUI, were used: a self-completed one for health professionals and teachers (15Q) to report assessments of children and 2 interviewer-administered ones, for child survivors (42Q) to report assessments about their own health status and parents (45Q) to report assessments about their children's health status. The original translations and reviews were accomplished with direct oversight by members of the HUI Group, to ensure conceptual equivalence. The instruments were then tested in Buenos Aires by application to staff of the hematology-oncology service, childhood cancer patients and the parents of childhood cancer patients. Several modifications were made based on these tests. We concluded that the translation and cultural adaptation of these instruments was adequate for use with the groups tested in a pilot survey of survivors of childhood cancer in Argentina.

Boron levels in man: preliminary evidence of genetic regulation and some implications for human biology.

Boron is a ubiquitous constituent of man's external environment. Levels of the element in human blood reflect both acute and chronic exposure, usually as dietary intake (food and drinking water). There is an absolute requirement for boron in vascular plants but evidence for biological essentiality in animals (including man) is limited. A high body burden of the element may be harmful, especially to young animals (including human neonates). Information on boron deficiency is scanty. It has been proposed that boron contributes to living systems by acting indirectly as a proton donor and that it exerts a particular influence on cell membrane structure and function. The present study examines the variation in blood levels within and between human sibships and provides some support for the possibility that boron metabolism is subject to genetic regulation.

Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia.

OBJECTIVE: To determine whether the osteopenia and unusual fractures observed in children with acute lymphoblastic leukemia (ALL) were related to the disease rather than to its treatment. DESIGN: Prospective analysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. METHODS: Biochemical indicators of mineral, endocrine, and vitamin D status were measured before initiation of therapy. Bone mass was determined radiographically and by dual-photon absorptiometry of the lumbar region of the spine (L2-L4). Correlations between clinical observations, leukemia variables, bone mass, and biochemical assessment were determined. RESULTS: At the time of diagnosis musculoskeletal pain was present in 36% of patients and was more common in children with CD10-positive leukemia and leukocyte counts less than 20 x 10(9) cells/L. Radiographic evidence of osteopenia and fractures was observed in 13% and 10% of children, respectively. The mean bone mineral content was normal. Bone mass measurement z scores correlated with plasma 1,25-dihydroxyvitamin D3 concentrations (r = 0.43, p < 0.05). Plasma calcium, magnesium, phosphorus, and 25-hydroxyvitamin D3 levels were normal. Low plasma osteocalcin (mean +/- SD, 1.6 +/- 1.6 nmol/L) and 1,25-dihydroxyvitamin D3 (33.4 +/- 26.4 pmol/L) values were observed. Parathyroid hormone levels were low in 14% of children. Hypercalciuria was detected in 64% of children. Urinary deoxypyridinoline was lower (p < 0.01) than in age-matched control subjects. Histomorphometric measurements of iliac bone showed abnormalities in mineralization in the biopsy specimens from three of nine children. CONCLUSION: Most children with ALL have alterations in bone metabolism and bone mass when first examined. These data suggest defective mineralization as the mechanism for decreased bone mass and implicate the leukemic process as causative.

The effect of war on tuberculosis. Results of a tuberculin survey among displaced persons in El Salvador and a review of the literature.

SETTING: During wartime, civilian populations usually experience a drop in caloric intake, disruption of housing, and a diminution in availability of medical services. These disturbances might be expected to result in increased reactivation of tuberculosis, which may result in increased transmission. Such privations occurred in El Salvador during its 1980-92 civil war, particularly among the 20% of the population, or over 1 million people, who were displaced. OBJECTIVE: (1) To estimate the rate of transmission of tuberculosis among displaced Salvadorians prior to and during the war, and (2) to compare this result with experience in the literature. DESIGN: (1) A tuberculin survey was conducted in El Salvador in July 1992 among all residents aged 1-30 years in 12 communities of formerly displaced persons. (2) The English language literature on tuberculosis during wartime was reviewed. RESULTS: (1) Overall, 21.2% of the non-BCG vaccinated had significant tuberculin reactions, equivalent to an annual risk of infection of 2.3%. The trend in the annual risk of infection was upward over the latter 6 years of the war, stable over the first 6 years, and was downward prior to the war years. The estimated incidence of smear positive pulmonary tuberculosis was 125 per 100,000 or 3 times the reported rate for El Salvador. (2) A review of the literature showed consistent evidence for increased morbidity and mortality from tuberculosis during wartime. Increased transmission was suggested by those studies showing a rise in both incidence of tuberculous meningitis during war years and excess morbidity and mortality many years after a war. Two major population-based studies found no evidence of increased transmission based on the calculated annual risk of infection; however other studies examining younger or more severely affected populations, or following more prolonged wars, detected an apparent increase in the transmission of tuberculosis. CONCLUSIONS: Conditions of war are associated with a rapid increase in morbidity and mortality from tuberculosis, which appears to result in increased transmission among populations most severely affected by war. This increased transmission will result in increased morbidity and mortality for many years, underscoring the need for improved tuberculosis control in the post-war period in countries such as El Salvador that have been devastated by war.

Regulation of lithium and boron levels in normal human blood: environmental and genetic considerations.

Blood lithium levels may be both genetically and environmentally regulated. The genetic component is evidenced mainly from studies in twins who were either normal or had a manic-depressive disorder. An environmental contribution is adduced from the relationship between the blood lithium level and the amount of the element ingested. No such information is available for boron, another element present in ultra trace amounts in human blood. Unusually high levels of lithium and boron in the waters of northern Chile offer an opportunity to study the genetic and environmental regulation of these elements in the blood of healthy subjects. Samples of blood (n = 40) and water (n = 47) were collected at seven locations in the province of Tarapaca. Most of the healthy subjects were Aymara who had been resident in the respective communities for at least 3 years. The samples were transported to Canada and then freeze-dried. Neutron irradiation was performed in a highly thermalized flux to induce the reactions 6Li (n, alpha) t and 10B (n,7Li) alpha. Assays of 6Li and 10B were conducted in a static mass spectrometer by measurement, respectively, of 3He, produced from decay of tritium, and 4He from alpha-particles. Lithium concentrations in water and blood exhibited a linear relationship, as did the boron concentrations in these fluids. Because some of the individual subjects (n = 15) were first-degree relatives, a genetic component to the regulation of blood levels was explored. The variance in blood levels of lithium and boron was significantly greater between than within families (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)