Association of Isolated Congenital Heart Disease with Fetal Brain Maturation.

BACKGROUND AND PURPOSE: Brain MRI of newborns with congenital heart disease show signs of immaturity relative to healthy controls. Our aim was to determine whether the semiquantitative fetal total maturation score can detect abnormalities in brain maturation in fetuses with congenital heart disease in the second and third trimesters. MATERIALS AND METHODS: We analyzed data from a prospective study of fetuses with and without congenital heart disease who underwent fetal MR imaging at 25-35 weeks' gestation. Two independent neuroradiologists blinded to the clinical data reviewed and scored all images using the fetal total maturation score. Interrater reliability was evaluated by the intraclass correlation coefficient using the individual reader scores, which were also used to calculate an average score for each subject. Comparisons of the average and individual reader scores between affected and control fetuses and relationships with clinical variables were evaluated using multivariable linear regression. RESULTS: Data from 69 subjects (48 cardiac, 21 controls) were included. High concordance was observed between readers with an intraclass correlation coefficient of 0.98 (95% CI, 0.97-0.99). The affected group had significantly lower fetal total maturation scores than the control group (ß-estimate, -0.9 [95% CI, -1.5 to -0.4], P = .002), adjusting for gestational age and sex. Averaged fetal total maturation, germinal matrix, myelination, and superior temporal sulcus scores were significantly delayed in fetuses with congenital heart disease versus controls (P < .05 for each). The fetal total maturation score was not significantly associated with any cardiac, anatomic, or physiologic variables. CONCLUSIONS: The fetal total maturation score is sensitive to differences in brain maturation between fetuses with isolated congenital heart disease and healthy controls.

Evaluating building-related symptoms using the US EPA BASE study results.

UNLABELLED: In order to develop baseline data about United States office buildings, the United States Environmental Protection Agency conducted the Building Assessment Survey Evaluation (BASE) study, a systematic survey of 100 randomly selected United States office buildings, in the 1990s. This paper analyzes the self-reported work-related symptoms and job and workplace characteristics of 4326 respondents and compares results to the National Institute for Occupational Safety and Health's (NIOSH) study of 80 'complaint' buildings. Four distinct groups of symptoms, representing 'tiredness', 'mucosal irritation', 'neuropsychological', and 'lower respiratory' conditions emerged from factor analysis of work-related symptoms. The symptom grouping is identical for both surveys. Although the prevalence of each symptom is significantly higher in the NIOSH than in the BASE sample, there is overlap of the symptom distributions. In the BASE survey, 45% of the work force reported at least one work-related health symptom; 20% reported at least three symptoms. These findings imply that it is counterproductive to dichotomize buildings into healthy vs. unhealthy; instead the prevalence of health problems related to buildings span a continuum. PRACTICAL IMPLICATIONS: These results indicate that most office buildings have occupants who report building-related symptoms. This paper provides practical guidance for the comparison of building prevalences to the BASE normative data. Work-related symptom distributions and symptom groups can improve investigators' ability to identify IEQ problems.

Distinct physiological states of Plasmodium falciparum in malaria-infected patients.

Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment.

Medical informatics in medical research - the Severe Malaria in African Children (SMAC) Network's experience.

OBJECTIVES: Computers are widely used for data management in clinical trials in the developed countries, unlike in developing countries. Dependable systems are vital for data management, and medical decision making in clinical research. Monitoring and evaluation of data management is critical. In this paper we describe database structures and procedures of systems used to implement, coordinate, and sustain data management in Africa. We outline major lessons, challenges and successes achieved, and recommendations to improve medical informatics application in biomedical research in sub-Saharan Africa. METHODS: A consortium of experienced research units at five sites in Africa in studying children with disease formed a new clinical trials network, Severe Malaria in African Children. In December 2000, the network introduced an observational study involving these hospital-based sites. After prototyping, relational database management systems were implemented for data entry and verification, data submission and quality assurance monitoring. RESULTS: Between 2000 and 2005, 25,858 patients were enrolled. Failure to meet data submission deadline and data entry errors correlated positively (correlation coefficient, r = 0.82), with more errors occurring when data was submitted late. Data submission lateness correlated inversely with hospital admissions (r = -0.62). CONCLUSIONS: Developing and sustaining dependable DBMS, ongoing modifications to optimize data management is crucial for clinical studies. Monitoring and communication systems are vital in multi-center networks for good data management. Data timeliness is associated with data quality and hospital admissions.

Human physiologic factors in respiratory uptake of 1,3-butadiene.

1,3-Butadiene (BD), a suspected human carcinogen, is used as the raw material in industries to make synthetic butyl rubber and plastics. Simulation models using experimental animal data have shown that physiologic factors play an important role in the kinetic behavior of BD. However, human data are limited. The aim of this inhalation study was to identify influential human physiologic factors in the respiratory uptake of BD. We recruited 133 healthy volunteers in Boston, Massachusetts, into this study and tested them under an approved human subjects protocol. Each subject was exposed to 2 ppm (4.42 mg/m3) BD for 20 min, followed by purified air for another 40 min. Five exhaled breath samples collected during exposure were used to determine the respiratory uptake of BD, which was defined as absorbed BD (micrograms) per kilogram of body weight during exposure. Although subjects were given identical administered doses (40 ppm x min), there was a wide range of uptake, 0.6-4.9 microg/kg. Of the studied physiologic factors, the blood:air partition coefficient and alveolar ventilation were most significant in determining the respiratory uptake (p < 0.001 for each). In addition, in the multiple regression analysis, females had significantly higher respiratory uptake of BD than males on a weight basis. For all subjects, increasing age and cigarette smoking led to significantly decreased respiratory uptake of BD. The results of this human study are consistent with previous kinetic simulations and animal studies. The findings also suggest that interindividual variation in human physiologic factors that affect the exposure-internal dose relationship should be considered while also exploring exposure-disease associations in future epidemiologic research.

General health status of children with D-transposition of the great arteries after the arterial switch operation.

BACKGROUND: To study the long-term impact on general health status of D-transposition of the great arteries (D-TGA) after the arterial switch operation (ASO) during infancy, we asked parents to complete the Child Health Questionnaire, Parent Form-50 when their children were 8 years old. METHODS AND RESULTS: Of 160 eligible patients, questionnaires were completed for 155 subjects (96%). Median age at surgery was 6 days (range 1 to 67 days), and median age at completion of the Child Health Questionnaire was 8.1 years (7.6 to 10.0 years). Subsequent to questionnaire completion, children underwent psychometric testing. Mean Physical Health Summary and Psychosocial Summary scores were 54.0+/-6.1 and 49.7+/-9.9, respectively, which were similar to those of normal subjects. Compared with the normative sample, parents of D-TGA patients reported more problems with attention, learning, and speech, as well as greater frequency of developmental delay (P<0.001 for each). Worse Psychosocial Summary scores were significantly associated with lower full-scale IQ (P=0.001) and lower achievement in reading (P=0.005) and math (P=0.007). Worse Physical Health Summary scores were associated with longer hospital stay after the ASO (P=0.02). General health status scores were not significantly related to presence of ventricular septal defect, age at surgery, perfusion variables during the ASO, sex, or history of cardiac reoperation. CONCLUSIONS: At age 8 years, children with D-TGA after ASO have an overall physical and psychosocial health status similar to that of the general population. Lower IQ and academic achievement are associated with worse psychosocial health status, whereas longer hospital course after initial surgery is associated with worse physical health status.

Dimensions of women's autonomy and the influence on maternal health care utilization in a north Indian city.

The dimensions of women's autonomy and their relationship to maternal health care utilization were investigated in a probability sample of 300 women in Varanasi, India. We examined the determinants of women's autonomy in three areas: control over finances, decision-making power, and freedom of movement. After we control for age, education, household structure, and other factors, women with closer ties to natal kin were more likely to have greater autonomy in each of these three areas. Further analyses demonstrated that women with greater freedom of movement obtained higher levels of antenatal care and were more likely to use safe delivery care. The influence of women's autonomy on the use of health care appears to be as important as other known determinants such as education.

Processing of rapid auditory stimuli in school-age children referred for evaluation of learning disorders.

Tallal hypothesized that reading disabled children have a domain-general deficit in processing rapidly occurring auditory stimuli that degrades speech perception, thereby limiting phonologic awareness and thus reading acquisition. She predicted they would be disproportionately affected by rapidly presented auditory stimuli. In this study, one hundred 7- to 11-year-old children with learning impairment (LI) and 243 non-learning impaired (NLI) children were evaluated on a two-tone auditory discrimination paradigm. LI committed more errors, but effects of timing were comparable. The same result was obtained for a subsample of good and poor readers. Task performance predicted reading, spelling, and calculation. Neural processes underlying perception of speech and other auditory stimuli may be less effective in poor readers; however, contrary to Tallal's hypothesis, rate may not be specifically affected.

Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.

OBJECTIVES: In a randomized single-center trial, we compared developmental and neurologic outcomes at 1 and 2 to 4 years of age in children who underwent reparative cardiac operations at less than 9 months of age after use of the alpha-stat versus pH-stat strategy during deep hypothermic cardiopulmonary bypass. METHODS: Among 168 children eligible for follow-up, 1-year developmental evaluations were carried out on 111, neurologic evaluations on 110, and electroencephalographic evaluations on 102. Parents of 122 children completed questionnaires on behavior and development when children were 2 to 4 years of age. RESULTS: The Psychomotor Development Index scores of the alpha-stat and pH-stat groups did not differ significantly (P =.97). For Mental Development Index scores, the treatment group effect differed according to diagnosis (P =.007). In the D -transposition of the great arteries (n = 59) and tetralogy of Fallot (n = 36) subgroups, the pH-stat group had slightly higher Mental Development Index scores than the alpha-stat group, although these differences were not statistically significant. In the ventricular septal defect subgroup (n = 16), the alpha-stat group had significantly higher scores. Psychomotor Development Index and Mental Development Index scores were significantly higher in the group with D -transposition of the great arteries than in the other 2 groups (P =.03 and P =.01, respectively). Across all diagnoses, Mental Development Index scores were significantly higher than Psychomotor Development Index scores (P <.001). Treatment group assignment was not significantly associated with abnormalities on neurologic examination (P =.70) or electroencephalographic examination (P =.77) at 1 year or with parents' ratings of children's development (P =.99) or behavior (P =.27) at age 2 to 4 years. CONCLUSIONS: Use of alpha-stat versus pH-stat acid-base management strategy during reparative infant cardiac operations with deep hypothermic cardiopulmonary bypass was not consistently related to either improved or impaired early neurodevelopmental outcomes.

Noninvasive detection of changes in cerebral blood flow by near-infrared spectroscopy in a piglet model of hydrocephalus.

Formulation of rational interventions in infantile hydrocephalus is limited by the inability to monitor cerebral hemodynamics quantitatively, continuously, and noninvasively. Near-infrared spectroscopy (NIRS) measures changes in cerebral concentration of oxygenated and deoxygenated hemoglobin (HbO(2) and Hb); HbD is the derived difference between HbO(2) and Hb. Our previous work showed that HbD reflected cerebral blood flow (CBF) measured by radioactive microspheres in a piglet model of systemic hypotension. This study was designed to determine whether NIRS detected important changes in cerebral perfusion and oxygenation in a piglet model of hydrocephalus and whether changes in HbD accurately reflected changes in CBF. Acute hydrocephalus was produced in neonatal piglets by intraventricular infusion of "mock cerebrospinal fluid." Intracranial pressure (ICP) was maintained for several minutes at approximately 10, 20, and 30 mm Hg above the baseline ICP. CBF was measured in cerebral cortex, white matter, and basal ganglia at each ICP by radioactive microspheres. Changes in HbO(2) and Hb were measured continuously by NIRS. Cerebral perfusion pressure declined with increasing ICP, and this decline was accompanied by significant decreases in HbD measured by NIRS and CBF measured by radioactive microspheres. There was a strong correlation between changes in HbD and individual changes in CBF in cerebral cortex, white matter, and basal ganglia (all p < 0.0001). This study demonstrates that changes in HbD reflect changes in CBF over a wide range of ICP in a model of acute hydrocephalus. This reproducible and easily obtained measurement by NIRS could facilitate considerably decisions concerning therapeutic interventions.

Diminished motor timing control in children referred for diagnosis of learning problems.

Disabled readers exhibit motor timing control (MTC) deficits in bimanual coordination relative to average readers. This article evaluates to what extent poor MTC is specific to reading or if it is related to learning problems in general. Children (7 to 11 years of age) referred for learning impairment (LI; n = 100) and same-age children nonlearning impaired (NLI; n = 243) performed a paced finger-tapping task. Greater variability of interresponse intervals was associated with poorer reading, spelling, and arithmetic achievement. The LI group performed more poorly than the NLI group, a difference that persisted even after adjusting for reading skill. Poor MTC is associated with poor reading but may also be a characteristic of children referred for learning problems, possibly signaling increased vulnerability of underlying neural integrative processes relevant to the child's adaptation to academic demands, including reading.

Impact of maternal depression on ratings of comorbid depression in adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: To assess the degree to which indirect maternal reports of comorbid major depression (MD) in adolescents with and without attention-deficit/hyperactivity disorder (ADHD) were influenced by the mother's personal history of MD. METHOD: Bivariate regression was used to model the impact of maternal depression on the direct and indirect report of MD in ADHD (n = 150) and non-ADHD (n = 123) subjects. The dependent variable (i.e., risk for MD) was modeled as a function of the main effect of ADHD, the main effect of reporter, their interaction, and higher-order interactions with maternal depression. RESULTS: There was a significant interaction between maternal depression and the effect of reporter exclusively in non-ADHD control subjects. ADHD continued to be a significant risk factor for MD independent of maternal reporting or maternal depression. CONCLUSIONS: The potential distortion of indirect interviews by depressed mothers may be stronger in community than in clinical settings and does not account for the increased risk for MD in referred adolescents with ADHD.

Cognitive impairment and mortality in the community-dwelling elderly.

The effects on mortality of cognitive impairment and 3-year declines in cognitive function were examined among community-dwelling adults aged 68 years or more. Data were taken from a population-based cohort study that enrolled noninstitutionalized elderly residents of New Haven, Connecticut, and followed them by conducting in-home interviews in 1982, 1985, 1988, and 1994. The cognitive function of 1,997 respondents was assessed by using the 30-point Mini-Mental State Examination in 1985; 1,372 respondents (86% of those alive) were retested in 1988. Responses were classified as high normal (28-30), low normal (24-27), mild impairment (18-23), or severe impairment (0-17); cognitive decline was defined as a transition to a lower category. After control for multiple potential confounders, both severe and mild cognitive impairment were strongly predictive of subsequent mortality among respondents aged less than 80 years. Upon closer examination, the elevated mortality risk was observed primarily among respondents whose cognitive decline was recent rather than among those whose cognitive performance was compromised but stable. Among respondents aged 80 years or more, declines to severe cognitive impairment were predictive of mortality, but it was not clear whether the decline per se signaled an unfavorable prognosis not accounted for by the resulting impairment level. Cognitive declines, especially those in the young elderly, have a marked adverse impact on survival.

Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.

BACKGROUND: It is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest (CA) or low-flow cardiopulmonary bypass. METHODS AND RESULTS: Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass. Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children (97%). Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA. The CA group scored lower on tests of motor function (gross motor, P=0.01; fine motor, P=0.03) and had more severe speech abnormalities (oromotor apraxia, P=0.007). Seizures in the perioperative period, detected either clinically or by continuous electroencephalographic monitoring, were associated with lower mean IQ scores (12.6 and 7.7 points, respectively) and increased risk of neurological abnormalities (odds ratios, 8.4 and 5.6, respectively). The performance of the full cohort was below expectations in several domains, including IQ, expressive language, visual-motor integration, motor function, and oromotor control. CONCLUSIONS: Use of CA to support vital organs during open heart surgery in infancy is associated, at the age of 4 years, with worse motor coordination and planning but not with lower IQ or with worse overall neurological status.

Self-reported sexual behaviour and HIV risk taking among men who have sex with men in Fortaleza, Brazil.

OBJECTIVES: To describe and identify sociodemographic and behavioural characteristics and other factors related to high-risk behaviour for HIV infection of men who have sex with men (MSM) living in Fortaleza, Brazil. METHODS: A survey was carried out among 400 MSM aged 14-65 years and recruited through the snowball technique or in gay-identified venues. A semi-structured questionnaire was conducted among them. Logistic regression analysis was used to model the dichotomous outcome (high risk or low risk). RESULTS: Forty-four per cent of the participants reported engaging in high-risk sexual behaviour in the previous year. MSM less informed about AIDS, reporting more sexual partners, reporting at least one female partner in the previous year, having anal sex as the favourite way to have sex, and having great enjoyment of unprotected anal sex were more likely to be engaged in risky behaviour. Twenty-three per cent of participants reported at least one sexual contact with women during the previous year. Two-thirds of men who had unprotected sex with their female partners also had unprotected anal sex with their male partners. CONCLUSIONS: A large proportion of MSM in Fortaleza still remain at elevated risk for contracting HIV infection. The factors predictive of high-risk sexual behaviour are significant in spreading HIV infection among the MSM population and also among their female partners. The lifestyles of these men are different to those of men from other parts of Brazil or outside the country. Preventive interventions need to be culturally and socially specific in order to be effective.

Does antenatal care make a difference to safe delivery? A study in urban Uttar Pradesh, India.

Evidence to support that antenatal screenings and interventions are effective in reducing maternal mortality has been scanty and studies have presented contradictory findings. In addition, antenatal care utilization is poorly characterized in studies. As an exposure under investigation, antenatal care should be well defined. However, measures typically only account for the frequency and timing of visits and not for care content. We introduce a new measure for antenatal care utilization, comprised of 20 input components covering care content and visit frequency. Weights for each component reflect its relative importance to better maternal and child health, and were derived from a survey of international researchers. This composite measure for antenatal care utilization was studied in a probability sample of 300 low to middle income women who had given birth within the last three years in Varanasi, Uttar Pradesh, India. Results showed that demarcating women's antenatal care status based on a simple indicator--two or more visits versus less--masked a large amount of variation in care received. Logistic regression analyses were conducted to examine the effect of antenatal care utilization on the likelihood of using safe delivery care, a factor known to decrease maternal mortality. After controlling for relevant socio-demographic and maternity history factors, women with a relatively high level of care (at the 75th percentile of the score) had an estimated odds of using trained assistance at delivery that was almost four times higher than women with a low level of care (at the 25th percentile of the score) (OR = 3.97, 95% CI = 1.96, 8.10). Similar results were obtained for women delivering in a health facility versus at home. This strong positive association between level of care obtained during pregnancy and the use of safe delivery care may help explain why antenatal care could also be associated with reduced maternal mortality.

PIP: A new measure for antenatal care utilization is introduced, comprised of 20 input components on care content and visit frequency. Weights for each component reflect the component's relative importance to better maternal and child health, and were derived from a survey of international researchers. The measure was studied in a probability sample of 300 low- to middle-income women who had given birth within the past 3 years in Varanasi, Uttar Pradesh, India. After controlling for relevant sociodemographic and maternity history factors, analysis of the data found that the use of antenatal care among low- to middle-income women in Varanasi positively influences the likelihood of using trained assistance at the birth of the child. Women with a relatively high level of care had an estimated odds of using trained assistance at delivery that was almost 4 times higher than women with a low level of care. Similar results were obtained for women delivering in a health facility rather than at home. This strong positive association between level of care during pregnancy and the use of safe delivery care may help explain why antenatal care could also be associated with reduced maternal mortality.

Differential perpetuation of malaria species among Amazonian Yanomami Amerindians.

To determine whether malaria perpetuates within isolated Amerindian villages in the Venezuelan Amazon, we surveyed malaria infection and disease among 1,311 Yanomami in three communities during a 16-month period. Plasmodium vivax was generally present in each of these small, isolated villages; asymptomatic infection was frequent, and clinical disease was most evident among children less than five years of age (odds ratio [OR] = 6.3, 95% confidence interval [CI] = 1.4-29.2) and among persons experiencing parasitemias > or = 1,000 parasites/mm3 of blood (OR = 45.0, 95% CI = 5.5-370.7). Plasmodium falciparum, in contrast, was less prevalent, except during an abrupt outbreak in which 72 infections resulted in symptoms in all age groups and at all levels of parasitemia, and occasionally were life-threatening. The observed endemic pattern of P. vivax infection may derive from the capacity of this pathogen to relapse, while the epidemic pattern of P. falciparum infection may reflect occasional introductions of strains carried by immigrants or residents of distant villages and the subsequent disappearance of this non-relapsing pathogen.

Self-reporting versus parental reporting of acute respiratory symptoms of children and their relation to pulmonary function and air pollution.

BACKGROUND: Studies of acute effects of outdoor air pollution on acute respiratory symptoms in children generally rely on reports by parents. Little is known about the validity of parental reporting of symptoms of their children. We therefore compared symptoms reported by the parents with self-reported symptoms and measured pulmonary function of 741 7-11-year-old Dutch children. We also analysed the association of symptoms reported by the child or parent and outdoor air pollution. METHODS: The parents of the children completed a daily diary of symptoms of their children for about 3 months. The children reported presence of acute respiratory symptoms in the preceding week before a pulmonary function test was conducted (6-10 test days). RESULTS: Children reported between 80% and 220% more acute respiratory symptoms than their parents for them in the same period. The agreement between symptom reports by the parent and the child was low to moderate (Kappa between 0.22 for eye irritation and 0.43 for fever). Presence of cough reported by child or parent was associated with similar small decrements in forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0) and especially peak expiratory flow (PEF) and maximal mid-expiratory flow (FEF25-75). The largest pulmonary function decrements were found when symptoms were reported by both parent and child. Symptoms reported by either child or parent were not associated with air pollution. CONCLUSIONS: Symptom reports of the children were more prevalent but did not agree well with parental reports. The similar association with pulmonary function suggested that self-reported symptoms were neither superior nor inferior to symptoms reported by the parents.

Assessment of coke oven emissions exposure among coking workers.

Coking workers are regularly exposed to coke oven emissions, which consist primarily of polycyclic aromatic hydrocarbons and volatile organic compounds. This study measured the workers' exposure to the benzene soluble fraction of total particulates (BSF). The study population consisted of 88 coking workers as an exposure group and 59 referents. Personal breathing-zone samples of BSF and total particulates were taken from all study subjects for 3 consecutive days. The highest BSF concentrations were found among the topside oven workers (geometric mean; range) (microgram/m3): lidman (515; 72-18, 181), tar chaser (432; 51-4334), and larry car operator (185; 55-649). The lowest was 7 micrograms/m3 in the referents. Among the samples at the topside oven 84% exceeded the Occupational Safety and Health Administration standard (150 micrograms/m3 BSF). The percentage of BSF in total particulates varied across job classifications, ranging from 0.3% in wharfmen to 24% in tar chasers. Area sampling indicated that the BSF concentration at the topside area was sixtyfold higher than that at the administrative area, which was approximately 2 km from the coke oven plant.