Biomedical subjects

Christopher Cox

Publications and source records attributed to Christopher Cox.

At least 19 recordsLinked to original sources

PubMed2007

Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats.

Epidemiological studies associate ambient particulate pollution with adverse health outcomes in elderly individuals with cardiopulmonary diseases. We hypothesized that freshly generated ultrafine particles (UFP) contribute to these effects, as they are present in high number concentrations on highways and vehicle passengers are exposed directly to them. Aged spontaneously hypertensive rats (9-12 mo) with implanted radiotelemetry devices were exposed to highway aerosol or filtered, gas-denuded (clean) air using an on-road exposure system to examine effects on heart rate (HR) and heart-rate variability (HRV). On the day of exposure, rats were pretreated with low-dose inhaled or injected lipopolysaccharide (LPS) to simulate respiratory tract or systemic inflammation, respectively. Exposures (6 h) in compartmentalized whole-body chambers were performed in an air conditioned compartment of a mobile laboratory on I-90 between Rochester and Buffalo, NY. HRV parameters were calculated from telemetric blood pressure signals and analyzed for the baseline period and for the first 32 h postexposure. The aerosol size (count median diameter = 15-20 nm; geometric standard deviation = 1.4-4.3) and number concentration (1.95-5.62 x 105/cm3) indicated the predominance of UFP. Intraperitoneal LPS significantly affected all of the parameters in a time-dependent manner; response patterns after inhaled or injected LPS pretreatment were similar, but more prolonged and greater in LPS-injected rats. A significant effect of highway aerosol was found, irrespective of pretreatment, which resulted in decreased HR in comparison to clean air-exposed rats. This effect was more persistent ( approximately 14 h) in those rats that received ip LPS as compared to saline. The highway aerosol also significantly affected short-term alterations in autonomic control of HR, as evidenced by elevations in normalized high frequency power and decreased vagosympathetic balance. These findings show that environmental exposure concentrations of mixed traffic-related UFP/gas-phase emissions can affect the autonomic nervous system.

Administration, Inhalation↗

PubMed2006

Papillomavirus-like particles are an effective platform for amyloid-beta immunization in rabbits and transgenic mice.

Immunization with amyloid-beta (Abeta) prevents the deposition of Abeta in the brain and memory deficits in transgenic mouse models of Alzheimer's disease (AD), opening the possibility for immunotherapy of AD in humans. Unfortunately, the first human trial of Abeta vaccination was complicated, in a small number of vaccinees, by cell-mediated meningoencephalitis. To develop an Abeta vaccine that lacks the potential to induce autoimmune encephalitis, we have generated papillomavirus-like particles (VLP) that display 1-9 aa of Abeta protein repetitively on the viral capsid surface (Abeta-VLP). This Abeta peptide was chosen because it contains a functional B cell epitope, but lacks known T cell epitopes. Rabbit and mouse vaccinations with Abeta-VLP were well tolerated and induced high-titer autoAb against Abeta, that inhibited effectively assembly of Abeta(1-42) peptides into neurotoxic fibrils in vitro. Following Abeta-VLP immunizations of APP/presenilin 1 transgenic mice, a model for human AD, we observed trends for reduced Abeta deposits in the brain and increased numbers of activated microglia. Furthermore, Abeta-VLP vaccinated mice also showed increased levels of Abeta in plasma, suggesting efflux from the brain into the vascular compartment. These results indicate that the Abeta-VLP vaccine induces an effective humoral immune response to Abeta and may thus form a basis to develop a safe and efficient immunotherapy for human AD.

Alzheimer Vaccines↗

PubMed2006

Hershey Medical Center Technical Workshop Report: optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure.

Neurodevelopmental disabilities affect 3-8% of the 4 million babies born each year in the U.S. alone, with known etiology for less than 25% of those disabilities. Numerous investigations have sought to determine the role of environmental exposures in the etiology of a variety of human neurodevelopmental disorders (e.g., learning disabilities, attention deficit-hyperactivity disorder, intellectual disabilities) that are manifested in childhood, adolescence, and young adulthood. A comprehensive critical examination and discussion of the various methodologies commonly used in investigations is needed. The Hershey Medical Center Technical Workshop: Optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure provided such a forum for examining these methodologies. The objective of the Workshop was to develop scientific consensus on the key principles and considerations for optimizing the design and interpretation of epidemiologic studies of in utero exposure to environmental chemicals and subsequent neurodevelopmental effects. (The Panel recognized that the nervous system develops post-natally and that critical periods of exposure can span several developmental life stages.) Discussions from the Workshop Panel generated 17 summary points representing key tenets of work in this field. These points stressed the importance of: a well-defined, biologically plausible hypothesis as the foundation of in utero studies for assessing neurodevelopmental outcomes; understanding of the exposure to the environmental chemical(s) of interest, underlying mechanisms of toxicity, and anticipated outcomes; the use of a prospective, longitudinal cohort design that, when possible, runs for periods of 2-5 years, and possibly even longer, in an effort to assess functions at key developmental epochs; measuring potentially confounding variables at regular, fixed time intervals; including measures of specific cognitive and social-emotional domains along with non-cognitive competence in young children, as well as comprehensive measures of health; consistency of research design protocols across studies (i.e., tests, covariates, and analysis styles) in an effort to improve interstudy comparisons; emphasis on design features that minimize introduction of systematic error at all stages of investigation: participant selection, data collection and analysis, and interpretation of results; these would include (but not be limited to) reducing selection bias, using double-blind designs, and avoiding post hoc formulation of hypotheses; a priori data analysis strategies tied to hypotheses and the overall research design, particularly for methods used to characterize and address confounders in any neurodevelopmental study; actual quantitative measurements of exposure, even if indirect, rather than methods based on subject recall; careful examination of standard test batteries to ensure that the battery is tailored to the age group as well as what is known about the specific neurotoxic effects on the developing nervous system; establishment of a system for neurodevelopmental surveillance for tracking the outcomes from in utero exposure across early developmental time periods to determine whether central nervous system injuries may be lying silent until developmentally challenged; ongoing exploration of computerized measures that are culturally and linguistically sensitive, and span the age range from birth into the adolescent years; routine incorporation of narrative in manuscripts concerning the possibility of spurious (i.e., false positive and false negative) test results in all research reportage (this can be facilitated by detailed, transparent reporting of design, covariates, and analyses so that others can attempt to replicate the study); forthright, disciplined, and intellectually honest treatment of the extent to which results of any study are conclusive--that is, how generalizable the results of the study are in terms of the implications for the individual study participants, the community studied, and human health overall; confinement of reporting to the actual research questions, how they were tested, and what the study found, and avoiding, or at least keeping to a minimum, any opinions or speculation concerning public health implications; education of clinicians and policymakers to critically read scientific reports, and to interpret study findings and conclusions appropriately; and recognition by investigators of their ethical duty to report negative as well as positive findings, and the importance of neither minimizing nor exaggerating these findings.

Biomedical Research↗

PubMed2006

Methylmercury and neurodevelopment: longitudinal analysis of the Seychelles child development cohort.

BACKGROUND: The Seychelles Child Development Study (SCDS) has been longitudinally following a cohort of over 700 children enrolled in 1989. Their mothers consumed a diet high in fish during pregnancy. Repeated examination of the SCDS cohort at six different ages through age 11 years has shown no pattern of adverse effects. Some early appearing beneficial associations between both prenatal and postnatal hair MeHg and several child development endpoints were noted. We hypothesized these might be related to micronutrients in the fish, but they were not found when the children reached middle school age. These findings suggest that the associations observed between MeHg and developmental outcomes may vary with developmental stage. METHOD: We examined the main cohort of the SCDS to determine if this might be true using a longitudinal multiple regression analysis design that focused on those endpoints that were repeatedly measured at different ages. The primary endpoint analyzed was global cognition, involving a measure of developmental quotient or IQ. Secondary analyses included other domains such as Reading and Mathematics scholastic achievement, social behavior, and memory. Analyses involved two different approaches, one including incorporation of a passage of time variable, the other including a difference of scores across time points. RESULTS: No significant associations were found between prenatal MeHg exposure and any of the repeatedly measured endpoints. CONCLUSIONS: These results suggest that even when individual subject variance is controlled there was no consistent pattern of associations between child development outcomes and prenatal exposures to MeHg from maternal consumption of a diet high in fish. The Seychellois diet contains about 10 times more ocean fish than is typically consumed by US citizens. Our primary focus on IQ should further inform growing scientific interest in the analysis of the risks and benefits of fish consumption on overall cognitive ability.

Child↗

PubMed2006

The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels.

Individuals homozygous for the thermolabile variant (677TT) of methylenetetrahydrofolate reductase exhibit reduced folate status as evidenced by a drop in the biomarker red cell folate (RCF) compared to those who carry at least one 677C allele. We now report that a different polymorphism in the same enzyme, namely 1298A>C, is associated with increased RCF levels. Thus, these two common polymorphisms change a metabolic phenotype in opposite directions suggesting that their cancer protective associations are by different mechanisms.

Biomarkers↗

PubMed2006

Prenatal methyl mercury exposure from fish consumption and child development: a review of evidence and perspectives from the Seychelles Child Development Study.

Evidence from an outbreak of methyl mercury (MeHg) poisoning in Iraq suggested that adverse effects of prenatal exposure on child development begin to appear at or above 10ppm measured in maternal hair. To test this hypothesis in a fish-eating population, we enrolled a cohort of 779 children (the main cohort) in the Seychelles Child Development Study (SCDS). The cohort was prenatally exposed to MeHg from maternal fish consumption, and the children started consuming fish products at about 1 year of age. Prenatal exposure was measured in maternal hair and recent postnatal exposure in the child's hair. The cohort has been examined six times over 11 years using extensive batteries of age-appropriate developmental tests. Analyses of a large number of developmental outcomes have identified frequent significant associations in the appropriate direction with numerous covariates known to affect child development, but only one adverse association between prenatal MeHg exposure and a developmental endpoint. Because such results could be ascribed to chance, there is no convincing evidence for an association between prenatal exposure and child development in this fish-eating population. Secondary analyses have generally supported the primary analyses, but more recently have suggested that latent or delayed adverse effects might be emerging at exposure above 10-12ppm as the children mature. This suggests that the association between prenatal exposure and child development may be more complex than originally believed. This paper reviews the SCDS main cohort study results and presents our current interpretations.

Animals↗

PubMed2006

Swimming pool drownings among US residents aged 5-24 years: understanding racial/ethnic disparities.

OBJECTIVE: We examined circumstances surrounding swimming pool drownings among US residents aged 5 to 24 years to understand why Black males and other racial/ethnic groups have high drowning rates. METHODS: We obtained data about drowning deaths in the United States (1995-1998) from death certificates, medical examiner reports, and newspaper clippings collected by the US Consumer Product Safety Commission. RESULTS: During the study period, 678 US residents aged 5 to 24 years drowned in pools. Seventy-five percent were male, 47% were Black, 33% were White, and 12% were Hispanic. Drowning rates were highest among Black males, and this increased risk persisted after we controlled for income. The majority of Black victims (51%) drowned in public pools, the majority of White victims (55%) drowned in residential pools, and the majority of Hispanic victims (35%) drowned in neighborhood pools (e.g., an apartment complex pool). Foreign-born males also had an increased risk for drowning compared with American-born males. CONCLUSIONS: Targeted interventions are needed to reduce the incidence of swimming pool drownings across racial/ethnic groups, particularly adult supervision at public pools.

Adolescent↗

PubMed2006

Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population.

The risk of neural tube defects (NTDs) is known to have a significant genetic component that could act through either the NTD patient and/or maternal genotype. The success of folic acid supplementation in NTD prevention has focused attention on polymorphisms within folate-related genes. We previously identified the 1958G>A (R653Q) polymorphism of the trifunctional enzyme MTHFD1 (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase; often referred to as 'C1 synthase') as a maternal risk for NTDs, but this association remains to be verified in a separate study to rule out a chance finding. To exclude this possibility, we genotyped an independent sample of mothers with a history of an NTD-affected pregnancy derived from the same Irish population. In this sample there was a significant excess of 1958AA homozygote mothers of NTD cases (n=245) compared to controls (n=770). The direction and magnitude of risk (odds ratio 1.49 (1.07-2.09), P=0.019) is consistent with our earlier finding. Sequencing of the MTHFD1 gene revealed that this association is not being driven by another common variant within the coding region. We have established that the MTHFD1 1958G>A polymorphism has a significant role in influencing a mother's risk of having an NTD-affected pregnancy in the Irish population.

Amino Acid Substitution↗

PubMed2006

Prospective identification of pregnant women drinking four or more standard drinks (> or = 48 g) of alcohol per day.

We aimed to identify drinking rates in a prospectively identified cohort of pregnant women, and subsequently, to identify the drinkers of 48 g or more alcohol/day among them, by using complementary methods for verifying self-reported drinking habits. A research team of social workers and health professionals at the Maipú Clinic, located in a lower middle class neighborhood of Santiago, Chile, conducted interviews of women attending a prenatal clinic between August 1995 and July 2000. Women whose interview responses met predefined criteria (identified in the text) were further evaluated by home visits. We interviewed 9,628 of 10,917 (88%) women receiving prenatal care. By initial interview, 42.6% of women reported no drinking, 57.4% some alcohol consumption, and 3.7% consuming at least one standard drink (15 mL of absolute alcohol) per day. Of the 887 women who had home visits, 101 were identified as consuming on average at least 4 drinks/day (48 g). To determine the best home visit questionnaire items for identifying those drinking at least 4 drinks per day, 48 women who openly admitted drinking this amount were compared with 786 women who were not considered drinkers after the home visit. The 48 self-reported 48 g/day drinkers were significantly more likely to get tipsy when drinking before (p = 0.01) or during (p < 0.0001) pregnancy, to have started drinking at a younger age (p = 0.007), or to exhibit signs of low self-esteem (p < 0.0001), sleep or appetite problems (p < 0.0001), bad interpersonal relationships (p < 0.0001) or having family members with fetal alcohol syndrome features (p < 0.009). In conclusion, using complementary methods of alcohol misuse ascertainment during pregnancy, we found that at least 1% of pregnant women in a Santiago, Chile, clinic population were drinking at levels that are clearly dangerous to the fetus (48 g/day or more). We identified specific interview questions that may help screen for alcohol use of 48 g/day or more in pregnant women.

Adolescent↗

PubMed2006

Locked plates combined with minimally invasive insertion technique for the treatment of periprosthetic supracondylar femur fractures above a total knee arthroplasty.

OBJECTIVE: New locked plate devices offer theoretical advantages for the treatment of supracondylar femur fractures associated with a total knee arthroplasty (TKA). These devices also can be inserted with relative ease by using minimally invasive techniques, provide a fixed angle construct, and improve fixation in osteoporotic bone. The purpose of this study was to evaluate the results and complications of treating periprosthetic supracondylar femur fractures above a TKA with a locked plate designed for the distal femur. DESIGN: Prospective, consecutive case series. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Twenty-two consecutive adult patients with 24 (2 bilateral) supracondylar femur fractures (OTA 33A) above a well-fixed non-stemmed TKA were treated with the Locking Condylar Plate. One patient who died before fracture healing and 1 who was lost to follow-up were excluded from analysis. All remaining patients (5 males, 15 females, average age, 73 (range, 50-95) years) were available for follow-up at an average of 15 (range, 6-45) months. According to the OTA classification, there were three 33A1, eight 33A2, and eleven 33A3 fractures. All fractures were closed. Indirect reduction methods without bone graft were used in all cases. RESULTS: Nineteen of 22 fractures healed after the index procedure (86%). All 3 patients with healing complications were insulin-dependent patients with diabetes who also were obese (body mass index >30). Two developed infected nonunions and 1 an aseptic nonunion. Postoperative alignment was satisfactory (within 5 degrees ) for 20 of 22 fractures. Fracture of screws in the proximal fragment occurred in 4 patients. In 3 of these cases, there was progressive coronal plane deformity. There was no change in alignment in any other patient. Fifteen of 17 patients who healed returned to their baseline ambulatory status, with 5 requiring additional ambulatory support compared with baseline. CONCLUSIONS: Fixation of periprosthetic supracondylar femur fractures with a locking plate provided satisfactory results in nondiabetic patients. Diabetic patients seem to be at high risk for healing complications and infection.

Aged↗

PubMed2006

The prevalence of Alzheimer neuropathologic lesions is similar in blacks and whites.

Alzheimer disease is the most common dementia in older Americans, but its impact on blacks is not clearly understood. We examined prospectively 200 autopsy brains at the Office of the Chief Medical Examiner in Maryland and compared the frequency and severity of Alzheimer lesions in blacks and whites. Histologic sections of the hippocampus and entorhinal and neocortices were immunostained for Abeta and tau proteins. Subjects were genotyped for ApoE. Abeta deposits were rated as none, sparse, moderate, or frequent; tau lesions were rated into 4 groups corresponding to Braak scores; and Abeta angiopathy was classified as present or absent. Outcome scores were treated as ordinal variables and analyzed by proportional odds logistic regression. Abeta plaques were present in 60% of black males, 58% of white males, 74% of black females, and 74% of white females. Tau lesions were present in 96% of black males, 88% of white males, 96% of black females, and 96% of white females. Neither race nor gender was a significant factor in the frequency or severity of Alzheimer lesions, and ApoE4 increased the risk for Alzheimer lesions similarly in blacks and whites.

Aged↗

PubMed2006

Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans.

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter approximately 25nm, geometric standard deviation approximately 1.6), for 2 hr, in three separate protocols: 10 microg/m3 at rest, 10 and 25 microg/m3 with exercise, and 50 microg/m3 with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 microg/m3 UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 microg/m3 UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4+ T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.

Adult↗

PubMed2006

A prospective study of psychological predictors of body fat gain among children at high risk for adult obesity.

OBJECTIVE: Limited data suggest that psychological factors, including binge eating, dieting, and depressive symptoms, may predispose children to excessive weight gain. We investigated the relationship between baseline psychological measures and changes in body fat (measured with dual-energy x-ray absorptiometry) over time among children thought to be at high risk for adult obesity. METHODS: A cohort study of a convenience sample of children (age: 6-12 years) recruited from Washington, DC, and its suburbs was performed. Subjects were selected to be at increased risk for adult obesity, either because they were overweight when first examined or because their parents were overweight. Children completed questionnaires at baseline that assessed dieting, binge eating, disordered eating attitudes, and depressive symptoms; they underwent measurements of body fat mass at baseline and annually for an average of 4.2 years (SD: 1.8 years). RESULTS: Five hundred sixty-eight measurements were obtained between July 1996 and December 2004, for 146 children. Both binge eating and dieting predicted increases in body fat. Neither depressive symptoms nor disturbed eating attitudes served as significant predictors. Children who reported binge eating gained, on average, 15% more fat mass, compared with children who did not report binge eating. CONCLUSIONS: Children's reports of binge eating and dieting were salient predictors of gains in fat mass during middle childhood among children at high risk for adult obesity. Interventions targeting disordered eating behaviors may be useful in preventing excessive fat gain in this high-risk group.

Absorptiometry, Photon↗

PubMed2006

Indirect reduction and plate fixation, without grafting, for periprosthetic femoral shaft fractures about a stable intramedullary implant. Surgical Technique.

BACKGROUND: The application of indirect reduction techniques has improved fracture-healing and reduced the need for bone-grafting compared with the outcomes of older, direct reduction techniques. We investigated the results of such indirect reduction techniques for the treatment of periprosthetic femoral shaft fractures. METHODS: Fifty consecutive patients with a femoral shaft fracture about a stable intramedullary implant (a Vancouver Type-B1 fracture) were treated with a protocol that included open reduction with use of indirect reduction techniques and internal fixation with a single lateral plate without structural allografting or other bone-grafting. Four patients died in the early postoperative period, and five had inadequate follow-up. The remaining forty-one patients (average age, seventy-two years) were evaluated clinically and radiographically at an average of twenty-four months. RESULTS: All fractures healed in satisfactory alignment at an average of twelve weeks (range, seven to twenty-three weeks) after the index procedure. One patient had one fractured cable and two others had one fractured screw, but all of the fractures healed without evidence of implant loosening or malalignment. There was one deep infection in the perioperative period. Thirty of the forty-one patients returned to their baseline ambulatory status. CONCLUSIONS: The results of this study support the use of indirect open reduction and internal fixation with a single extraperiosteal lateral plate, without the use of allograft struts, for the treatment of a femoral shaft fracture about a stable intramedullary implant.

Adult↗

PubMed2005

Reduced folate carrier polymorphisms and neural tube defect risk.

The reduced folate carrier (RFCI) is essential for folate transport into cells. Low folate is an important cause of neural tube defects (NTDs), and a single-nucleotide polymorphism (H27R) (80G-->A) in the RFCI gene has been reported to be a NTD risk factor. We investigated H27R and a 61 bp tandem repeat polymorphism as potential risk factors for NTDs, using a large homogeneous Irish population by case/control comparison, log-linear analysis, and transmission disequilibrium testing. No association was found between NTDs and H27R in mothers [p = 0.23, odds ratio (OR) 0.87, 95% confidence interval (CI) 0.69-1.09], fathers (p = 0.11, OR 0.83, 95% CI 0.66-1.04), or cases (p = 0.36, OR 0.9, 95% CI 0.72-1.12) when compared to controls or through log-linear modeling for dominant or recessive effects or with the transmission disequilibrium test for preferential allele transmission. Using log-linear models, a significant protective case effect was seen for the 61 bp polymorphism (p = 0.0039, OR 0.21, 95% CI 0.05-0.85). When analyzed by genotype, individuals homozygous for a single copy of the 61 bp sequence were underrepresented in cases as compared to controls, although these results did not reach statistical significance (p = 0.081, OR 0.5, 95% CI 0.23-1.09, goodness of fit p = 0.42). We compared the frequencies of H27R and the 61 bp polymorphism in African-Americans and American-Caucasians. The frequencies of H27R polymorphism differed significantly between the two populations (p = 0.0001). This large study does not confirm previous reports that H27R is a risk factor for NTDs. The previously unstudied 61 bp tandem repeat, however, has a possible protective NTD effect in our Irish population. This requires confirmation in other studies.

Black or African American↗

PubMed2005

Screening for new MTHFR polymorphisms and NTD risk.

The enzyme, 5,10-methylenetetrahydrofolate reductase (MTHFR) plays a key role in cellular folate metabolism. The A222V (677C->T) polymorphism is a confirmed neural tube defect (NTD) risk factor within Irish and other populations. To search for other unknown single nucleotide polymorphisms (SNPs) that might play a role in the etiology of NTDs, we examined the entire MTHFR coding region in healthy individuals (n = 100). SNPs were identified using sequencing and database analysis and allele frequencies were determined in our Irish population. We identified P39P (116C->T; T allele frequency 0.13) and previously reported R594Q (1793G->A; Q allele frequency 0.07). We screened a large ethnically homogeneous Irish NTD cohort (n>1,300) for P39P and R594Q. A possible association between NTD cases and P39P (P = 0.034) was found but this was not confirmed by transmission disequilibrium testing. R594Q also showed some evidence of a NTD case association (P = 0.07). Further analysis indicated these observations are due to linkage disequilibrium with A222V (677C->T), and therefore these new SNPs are unlikely to be independent risk factors for NTDs. As rates of NTDs differ between ethnic groups, we examined allele and genotype frequencies of P39P and R594Q within African-American and American-Caucasian populations. This is the first NTD association study of both R594Q and the novel P39P. The association with NTD risk reported for these SNPs is driven by the linkage disequilibrium with the A222V (677C->T) NTD risk factor.

Base Sequence↗

PubMed2005

Folate-related genes and omphalocele.

Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C-->T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required.

Adult↗

PubMed2005

Respiratory syncytial virus infection in elderly and high-risk adults.

BACKGROUND: Respiratory syncytial virus (RSV) is an increasingly recognized cause of illness in adults. Data on the epidemiology and clinical effects in community-dwelling elderly persons and high-risk adults can help in assessing the need for vaccine development. METHODS: During four consecutive winters, we evaluated all respiratory illnesses in prospective cohorts of healthy elderly patients (> or =65 years of age) and high-risk adults (those with chronic heart or lung disease) and in patients hospitalized with acute cardiopulmonary conditions. RSV infection and influenza A were diagnosed on the basis of culture, reverse-transcriptase polymerase chain reaction, and serologic studies. RESULTS: A total of 608 healthy elderly patients and 540 high-risk adults were enrolled in prospective surveillance, and 1388 hospitalized patients were enrolled. A total of 2514 illnesses were evaluated. RSV infection was identified in 102 patients in the prospective cohorts and 142 hospitalized patients, and influenza A was diagnosed in 44 patients in the prospective cohorts and 154 hospitalized patients. RSV infection developed annually in 3 to 7 percent of healthy elderly patients and in 4 to 10 percent of high-risk adults. Among healthy elderly patients, RSV infection generated fewer office visits than influenza; however, the use of health care services by high-risk adults was similar in the two groups. In the hospitalized cohort, RSV infection and influenza A resulted in similar lengths of stay, rates of use of intensive care (15 percent and 12 percent, respectively), and mortality (8 percent and 7 percent, respectively). On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, Clinical Modification at discharge, RSV infection accounted for 10.6 percent of hospitalizations for pneumonia, 11.4 percent for chronic obstructive pulmonary disease, 5.4 percent for congestive heart failure, and 7.2 percent for asthma. CONCLUSIONS: RSV infection is an important illness in elderly and high-risk adults, with a disease burden similar to that of nonpandemic influenza A in a population in which the prevalence of vaccination for influenza is high. An effective RSV vaccine may offer benefits for these adults.

Adult↗