Biomedical subjects

Louise Ryan

Publications and source records attributed to Louise Ryan.

34 records · Page 2Linked to original sources

PubMed2003

Mixed models for assessing correlation in the presence of replication.

The need to assess correlation in settings where multiple measurements are available on each of the variables of interest often arises in environmental science. However, this topic is not covered in introductory statistics texts. Although several ad hoc approaches can be used, they can easily lead to invalid conclusions and to a difficult choice of an appropriate measure of the correlation. Lam et al. approached this problem by using maximum likelihood estimation in cases where the replicate measurements are linked over time, but the method requires specialized software. We reanalyze the data of Lam et al. using PROC MIXED in SAS and show how to obtain the parameter estimates of interest with just a few lines of code. We then extend Lam et al.'s method to settings where the replicate measurements are not linked. Analysis of the unlinked case is illustrated with data from a study designed to assess correlations between indoor and outdoor measurements of benzene concentration in the air.

Environmental Monitoring↗

PubMed2003

Low preconception body mass index is associated with birth outcome in a prospective cohort of Chinese women.

Low maternal prepregnancy BMI is associated with adverse birth outcomes, but the BMI at which risk increases is not well defined. We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospective study in Anhui, China. The women (n = 575) were 20-34 y old, married, nulliparous and nonsmokers. All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22-23 kg/m2. Infants born to the 27% of women who were severely underweight before pregnancy (BMI < or = 18.5 kg/m2) were at increased risk for fetal growth deficits associated with infant morbidity. Compared with a normal BMI, being severely underweight was associated with mean (+/- SEM) reductions of 219 +/- 40 g in infant birthweight and 6.7 +/- 1.3% in the birthweight ratio and an 80% increase in risk of intrauterine growth restriction [odds ratio (OR) 1.8; 95% CI: 1.0, 3.3; P = 0.05]. Being severely underweight was also associated with smaller infant head circumference and lower ponderal index. Being moderately underweight (18.5 < BMI < 19.8 kg/m2) was not significantly associated with adverse pregnancy outcomes. Gestational age and risk of preterm birth were not associated with maternal BMI. More than half of the women in this study were underweight before pregnancy. Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes, being severely underweight was an important risk factor for reduced fetal growth.

Adult↗

PubMed2003

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.

Adult↗

PubMed2003

The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p'-DDE.

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.

Adult↗

PubMed2003

Phthalate exposure and human semen parameters.

BACKGROUND: There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. METHODS: We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (< 20 million/ml) and motility (< 50% motile), as well as Tygerberg Strict criteria for morphology (< 4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. RESULTS: There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0; P-value for trend = 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend = 0.07). In addition, there was a dose-response relation between tertiles of mono-benzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend = 0.02). CONCLUSIONS: There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates.

Adult↗

PubMed2002

Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years.

Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.

Age Distribution↗

PubMed2002

Exposure to cat allergen, maternal history of asthma, and wheezing in first 5 years of life.

We looked for an association between early exposure to pets and asthma and wheezing in children whose mothers or fathers did or did not have a history of asthma. We followed up 448 children, who had at least one parent with a history of atopy, from birth to 5 years. Among children whose mothers had no history of asthma, exposure to a cat or a Fel d 1 concentration of at least 8 microg/g at the age of 2-3 months was associated with a reduced risk of wheezing between the ages of 1 and 5 years. However, among children whose mothers did have a history of asthma, such exposures were associated with an increased risk of wheezing at or after the age of 3 years. There was no association between wheezing and exposure to dog or dog allergen, and the father's allergy status had no effect on the relation between childhood wheezing and cat exposure.

Allergens↗

PubMed2002

Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years.

Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood. We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth. After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio [OR] for one versus no courses of antibiotics, 0.5; 95% confidence interval [CI] for OR, 0.2 to 1.5; OR for two or more versus no courses of antibiotics, 1.0; 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years. There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7; 95% CI, 0.4 to 1.4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood.

Administration, Oral↗

PubMed2002

Day care attendance, respiratory tract illnesses, wheezing, asthma, and total serum IgE level in early childhood.

BACKGROUND: It has been hypothesized that day care--related infections may explain the inverse relation between day care attendance in early life and asthma in childhood. OBJECTIVE: To examine the relation between day care attendance or respiratory tract illnesses in the first year of life and wheezing and asthma in the first 4 years of life among children with a parental history of atopy who were followed up from birth. RESULTS: Day care attendance in the first year of life was inversely associated with geometric mean total serum IgE level (12.9 [+/-1 SD = 3.3, 51.4] IU/mL for day care vs 18.5 [[+/-1 SD = 5.3, 64.7] IU/mL for no day care; P =.03) at 2 years of age but not significantly associated with wheezing at or after 2 years of age. Having at least 1 physician-diagnosed lower respiratory tract illness in the first year of life was significantly associated with recurrent wheezing (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.0-4.1) and asthma (OR, 2.5; 95% CI, 1.1-5.5) at 4 years of age, but not with any wheezing (infrequent and frequent) at 3 years or older. Illnesses of the upper respiratory tract (> or = 1 physician-diagnosed upper respiratory tract illness or > or = 3 episodes of nasal catarrh) in the first year of life were associated with any wheezing (frequent and infrequent) between the ages of 1 and 4 years, but not with recurrent wheezing or asthma at 4 years of age. CONCLUSIONS: Our results suggest that among children with a parental history of atopy the protective effect of day care attendance in early life against the development of atopy has begun by 2 years of age, and that a protective effect of day care attendance in early life against wheezing may not be observed until after 4 years of age.

Asthma↗

PubMed2002

Caretaker-child concordance for child's exposure to violence in a preadolescent inner-city population.

BACKGROUND: Effective screening for exposure to violence (ETV) in the pediatric setting depends on informant reliability and recognition of patients at increased risk. Pediatricians screening for children's ETV often rely on parent reporting. HYPOTHESIS: That there would be poor caretaker-child concordance given that children would report events occurring outside the home not witnessed by the caretaker and that ETV would be higher among immigrant families. OBJECTIVES: To examine concordance between caretaker and child self-report of the child's ETV in a preadolescent population and to explore factors related to increased risk. DESIGN: Community-based survey. SETTING: Urban community health center. PARTICIPANTS: One hundred sixty-five caretaker-child pairs. METHODS: The ETV was assessed by means of a standardized interview questionnaire on location and frequency of ETV. A Rasch model was used to develop summary scores of ETV (frequency and severity). RESULTS: Caretaker-child concordance on reports of child's ETV was poor. The kappa statistics ranged from -0.04 for seeing someone knifed to 0.39 for witnessing a shooting. Children reported ETV more often in their neighborhood or at school, whereas caretakers reported more events near or at home. Univariate predictors of child's self-reported ETV were female sex (beta +/- SE, -10.1 +/- 4.6; P =.03) and caretaker being divorced (beta +/- SE, 12.6 +/- 6.0; P =.04). In multivariate analyses, country of origin predicted child's ETV, adjusting for child's age and sex, and caretaker educational status and marital status. CONCLUSIONS: Caretakers and their children have poor agreement on reports of the child's ETV. Intervention strategies around ETV should include assessment of the child independent of caretaker report for preadolescents. Screening may be more effective if pediatricians are aware of factors related to increased risk, including immigration status and caretaker marital status.

Adolescent↗

PubMed2002

A longitudinal analysis of wheezing in young children: the independent effects of early life exposure to house dust endotoxin, allergens, and pets.

BACKGROUND: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. OBJECTIVE: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. METHODS: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. RESULTS: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95 % CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend =.005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. CONCLUSION: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.

Air Pollution, Indoor↗

PubMed2002

Modeling spatial survival data using semiparametric frailty models.

We propose a new class of semiparametric frailty models for spatially correlated survival data. Specifically, we extend the ordinary frailty models by allowing random effects accommodating spatial correlations to enter into the baseline hazard function multiplicatively. We prove identifiability of the models and give sufficient regularity conditions. We propose drawing inference based on a marginal rank likelihood. No parametric forms of the baseline hazard need to be assumed in this semiparametric approach. Monte Carlo simulations and the Laplace approach are used to tackle the intractable integral in the likelihood function. Different spatial covariance structures are explored in simulations and the proposed methods are applied to the East Boston Asthma Study to detect prognostic factors leading to childhood asthma.

Asthma↗

PubMed2002

Environmental organochlorines and semen quality: results of a pilot study.

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.

Adult↗

PubMed2002

Bottle feeding in the bed or crib before sleep time and wheezing in early childhood.

OBJECTIVE: Bottle feeding in the bed or crib before sleep time has been associated with an increased risk of wheezing in the first year of life. We examined whether bottle feeding in the bed or crib before sleep time in the first year of life is associated with wheezing in the first 5 years of life. METHODS: In a prospective cohort study of 448 children with parental history of atopy followed from birth, we examined the relation between the number of bimonthly parental reports of bottle feeding in the bed or crib before sleep time in the first year of life (range: 0-6 reports) and parental report of wheezing in the first 5 years of life. Additional outcome measures included recurrent wheezing (> or =2 episodes of wheezing in the previous year) and asthma (physician-diagnosed asthma and > or =1 episode of wheezing in the previous year) at the age of 5 years. RESULTS: The risk of recurrent wheezing and asthma at 5 years of age increased significantly with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. The risk of wheezing between the ages of 1 and 5 years increased with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. As an example, a child whose parents reported bottle feeding in the bed or crib before sleep time on 3 occasions in the first year of life had 1.5 times higher risk of wheezing between the ages of 1 and 5 years than a child whose parents did not report bottle feeding in the bed or crib before sleep time in the first year of life (95% confidence interval for relative risk: 1.12-2.12). CONCLUSIONS: Among children with parental history of atopy, bottle feeding in the bed or crib before sleep time in the first year of life is a risk factor for recurrent wheezing and asthma at 5 years of age and a risk factor for wheezing between the ages of 1 and 5 years.

Breast Feeding↗

PubMedDate not supplied

The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters.

The general population is exposed to phthalates through consumer products, diet, and medical devices. The present study explored whether phthalates, reproductive toxins in laboratory animals, were associated with altered sperm movement characteristics in men. Two-hundred twenty subjects provided a semen sample for computer-aided sperm analysis (CASA) and a urine sample for measurement of phthalate monoesters, monoethyl (MEP), monobenzyl (MBzP), mono-n-butyl (MBP), mono-2-ethylhexyl (MEHP), and monomethyl (MMP). Three CASA parameters, straight-line velocity (VSL), curvilinear velocity (VCL), and linearity (LIN), were used as measures of sperm progression, sperm vigor, and swimming pattern, respectively. There were suggestive dose-response relationships (shown as the predicted change in mean sperm motion parameter for the second and third tertiles compared with the first tertile; P value for trend) for MBzP with VSL (-2.36 microm/s, -2.81 microm/s; P =.09) and VCL (-1.67 microm/s, -2.45 microm/s; P =.4). There were suggestive negative associations between MBP and VSL (-3.07 microm/s, -2.87 microm/s; P =.08) and VCL (-3.25 microm/s, -3.46 microm/s; P =.2), and between MEHP with VSL (-1.09 microm/s, -2.73 microm/s; P =.1) and VCL (-0.29 microm/s, -2.93 microm/s; P =.3). In contrast to the other phthalates, MEP was positively associated with VSL and VCL but negatively associated with LIN. No consistent relationship was found for MMP and any sperm motion parameter. Although we did not find statistically significant associations, trends between CASA parameters, sperm velocity, and forward progression, and increased urinary levels of MBP, MBzP, and MEHP warrant further follow-up.

Adult↗

PubMedDate not supplied

Parental exposure to organic solvents and reduced birth weight.

The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.

Adult↗