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PubMed1998

Amperometric phenol biosensor based on a thermostable phenol hydroxylase.

Phenol hydroxylase (EC 1.14.13.7) was produced using Bacillus stearothermophilus in a 5-1 batch fermentation leading to approximately 17 units after 6 h. The partially purified phenol hydroxylase was entrapped in a sol-gel matrix. The enzyme-loaded silica gel was attached to the sensitive top of a Clark-type oxygen electrode and its application as a phenol biosensor was tested. There was linearity between the maximal rate of oxygen consumption and phenol concentration in the range between 2.5 and 400 microM at 40 degrees C and pH 7.6. The signal could be read off after 10 s at a concentration of 400 microM phenol. The sensor lost 20% of its activity within 7 days. Para-substituted phenols were not detectable.

Biosensing Techniques↗
PubMed2000

A limited sampling strategy for determining carboplatin AUC and monitoring drug dosage.

There are several convincing reports showing relationships between the area under the curve of ultrafilterable concentration versus time (AUC) and pharmacodynamics of carboplatin. It is advisable, in treated patients, to check the AUC that is effectively delivered as compared with the prescribed AUC. To this end, limited sampling strategy seems to be an adequate approach since it limits the constraints of repeated blood sampling for both patients and nursing staff. A flexible limited sampling method for assessing ultrafilterable carboplatin AUC was developed. This method was based on a Bayesian estimation of carboplatin clearance using the NON linear Mixed Effect Model (NONMEN) program and a large pharmacokinetic and covariates database (103 patients). The optimal sampling design was a two-sample schedule (1 and 4 h after the end of infusion). During a prospective evaluation, it allowed an adequate estimation of carboplatin clearance with a non-significant bias (-4.5%) and a good precision (9%). In a second stage, this method was clinically applied to monitor carboplatin AUC in a group of 5 patients with metastatic germ cell tumours treated with intensified high dose carboplatin-based chemotherapy for 4 days. Dosage adjustments were performed according to daily controls of their AUC in order to obtain a total AUC of 20 mg/ml x min. By using this strategy all patients effectively received a total AUC very close to this targeted AUC, thus proving the clinical usefulness of this limited sampling method.

Antineoplastic Agents↗
PubMed2003

Change in quality of life from before to after discharge following left ventricular assist device implantation.

BACKGROUND: Quality of life (QOL) outcomes after left ventricular assist device (LVAD) implantation from before to after hospital discharge have been examined only in a very small sample of patients. The purposes of this study are to describe change in QOL from before to after hospital discharge in LVAD patients and to determine whether being discharged with an LVAD predicts better QOL than being hospitalized with an LVAD. METHODS: A non-random sample of 62 LVAD patients (approximately 50 years old, male, white, married, fairly well-educated) completed self-report questionnaires at >or=2 timepoints post-implant. The questionnaires (Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, Sickness Impact Profile, LVAD Stressor Scale, Jalowiec Coping Scale), which were collated into booklets, had acceptable reliability and validity. Longitudinal analyses were performed in 2 steps using 1-sample t-tests and linear mixed effects modeling. RESULTS: Perception of QOL and health status were fairly good both before and after discharge of LVAD patients. Discharge predicted increased satisfaction with socioeconomic areas of life; decreased overall and psychologic stress and stress related to family and friends, self-care and work/school/finances; and decreased physical and self-care disability. CONCLUSIONS: QOL outcomes improved from before to after hospital discharge in LVAD patients awaiting heart transplantation. As LVADs potentially become available as destination therapy, in addition to being successful bridges to heart transplantation, QOL outcomes will become more important to study.

Attitude to Health↗
PubMed1997

Relationship of seizure duration to antidepressant efficacy in electroconvulsive therapy.

BACKGROUND: A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it. METHODS: We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account. RESULTS: Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings. CONCLUSIONS: The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy.

Adolescent↗
PubMed2006

Significant enhancement of monooxygenase activity of oxygen carrier protein hemocyanin by urea.

Oxygenation of a series of p-substituted phenols to the corresponding catechols (phenolase activity) by the (mu-eta2:eta2-peroxo)dicopper(II) species of Octopus hemocyanin has been directly examined for the first time by using a UV-vis spectroscopic method in a 0.5 M borate buffer solution containing 8 M urea under anaerobic conditions. Preliminary kinetic studies have indicated that the reaction involves an electrophilic aromatic substitution mechanism as in the case of phenolase reaction of tyrosinase. The oxygenation of phenols by hemocyanin also proceeded catalytically when the reaction was carried out under aerobic conditions.

Animals↗
PubMed2002

Nonparametric AUC estimation in population studies with incomplete sampling: a Bayesian approach.

The estimation of the AUC in a population without frequent and/or fixed individual samplings is of interest because the number of plasma samples can often be limited due to technical, ethical and cost reasons. Non-linear mixed effect models can provide both population and individual estimates of AUC based on sparse sampling protocols; however, appropriate structural models for the description of the pharmacokinetics are required. Nonparametric solutions have also been proposed to estimate the population AUC and the associated error when particular sampling protocols are adopted. However, they do not estimate the individual AUCs and lack flexibility. Also a semiparametric method has been proposed for addressing the problem of sparse sampling in reasonably well designed studies. In this work, we propose and evaluate a nonparametric Bayesian scheme for AUC estimation in population studies with arbitrary sampling protocols. In the stochastic model representing the whole population, the individual plasma concentration curves and the "mean" population curve are described by random walk processes, allowing the application of the method to the reconstruction of any kind of "regular" curves. Population and individual AUC estimation are performed by numerically computing the posterior expectation through a Markov chain Monte Carlo algorithm.

Algorithms↗
PubMed2003

Factors associated with an optimal pregnancy outcome in an oocyte donation program.

PURPOSE: To identify donor and recipient variables that may have a significant impact on pregnancy outcome in order to optimize results of an oocyte donation program. METHOD: Retrospective analysis through a Generalized Estimating Equation (GEE) approach to clustered and binary clustered data, linear mixed effects model, scatter plot smoothing functions, and receiving operator characteristics (ROC) curves. SETTING: University-based center. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. PATIENTS: 257 donation and transfer cycles. RESULT(S): Overall results were as follows: clinical pregnancy rate, 47%; implantation rate, 22%; abortion rate, 19%; and overall multiple pregnancy rate, 35%. The total reproductive potential was 60%. Implantation and pregnancy rates were not significantly related to any variable from donors or recipients. Abortion rate increased significantly with donors' increased basal serum LH. Pregnancy rate was significantly enhanced with improved embryo quality. In donors stimulated more than once, the pregnancy rate was 84%. CONCLUSION(S): Although no single or combined donor or recipient variable(s) could be identified as predictor(s) of pregnancy, the data suggest that donors < or = 33 years of age with basal cycle day 3 serum levels of FSH 4-8 IU/L, LH < 8 IU/L, and E2 < 70 pg/mL had an optimal outcome. Transfer of two selected embryos on day 3 yields a favorable pregnancy outcome while significantly decreasing the occurrence of multiple pregnancies. These policies, in addition to embryo cryopreservation, were associated with optimal pregnancy outcome in oocyte donation.

Adult↗
PubMed2003

Efficacy of the RECAP intervention program for children with concurrent internalizing and externalizing problems.

The authors evaluated the efficacy of RECAP, a psychosocial intervention developed to treat concurrent internalizing and externalizing problems in children. Participants included 93 4th-grade children assigned to the treatment group or a no-treatment control group. The school-based program, which lasts the 9-month academic year, provides individual, group, classroom, teacher, and parent training in the RECAP skills-development curriculum, which was derived from empirically supported treatment programs for nonconcurrent internalizing and externalizing problems. Outcome assessments included parent-, teacher-, self-, and peer reports. A mixed hierarchical linear models analysis indicated that, overall, treatment children's rate of improvement in both internalizing and externalizing problems was significantly greater than that for control participants.

Child↗
PubMed2005

Using multilevel models to analyze couple and family treatment data: basic and advanced issues.

Couple and family treatment data present particular challenges to statistical analyses. Partners and family members tend to be more similar to one another than to other individuals, which raises interesting possibilities in the data analysis but also causes significant problems with classical, statistical methods. The present article presents multilevel models (also called hierarchical linear models, mixed-effects models, or random coefficient models) as a flexible analytic approach to couple and family longitudinal data. The article reviews basic properties of multilevel models but focuses primarily on 3 important extensions: missing data, power and sample size, and alternative representations of couple data. Information is presented as a tutorial, with a Web appendix providing datasets with SPSS and R code to reproduce the examples.

Couples Therapy↗
PubMed2004

Energy-dense snack food intake in adolescence: longitudinal relationship to weight and fatness.

OBJECTIVE: The longitudinal relationship between the consumption of energy-dense snack (EDS) foods and relative weight change during adolescence is uncertain. Using data from the Massachusetts Institute of Technology Growth and Development Study, the current analysis was undertaken to examine the longitudinal relationship of EDS food intake with relative weight status and percentage body fat and to examine how EDS food consumption is related to television viewing. RESEARCH METHODS AND PROCEDURES: One hundred ninety-six nonobese premenarcheal girls 8 to 12 years old were enrolled between 1990 and 1993 and followed until 4 years after menarche. At each annual follow-up visit, data were collected on percentage body fat (%BF), BMI z score, and dietary intake. Categories of EDS foods considered were baked goods, ice cream, chips, sugar-sweetened soda, and candy. RESULTS: At study entry, girls had a mean +/- SD BMI z score of -0.27 +/- 0.89, consumed 2.3 +/- 1.7 servings of EDS foods per day, and consumed 15.7 +/- 8.1% of daily calories from EDS foods. Linear mixed effects modeling indicated no relationship between BMI z score or %BF and total EDS food consumption. Soda was the only EDS food that was significantly related to BMI z score over the 10-year study period, but it was not related to %BF. In addition, a significant, positive relationship was observed between EDS food consumption and television viewing. DISCUSSION: In this cohort of initially nonobese girls, overall EDS food consumption does not seem to influence weight status or fatness change over the adolescent period.

Adipose Tissue↗
PubMed2003

Measured haplotype analysis of the aldosterone synthase gene and heart size.

Gene-association studies of heart size and the aldosterone synthase (CYP11B2) gene have produced inconsistent results, possibly because of limitations in the sample size and/or the number and location of the polymorphisms. An analysis of six polymorphisms spanning 6 kb of the CYP11B2 gene in Caucasian British families revealed a limited number of haplotypes because of strong linkage disequilibrium over this small region. The genotype and haplotype information was used in an association study involving 955 members of 229 families phenotyped for echocardiographic measures of heart size. In a mixed effects linear modelling analysis, the G5937C polymorphism was associated with cardiac wall thickness (P=0.02), and the intron conversion and A4550C polymorphisms were associated with left ventricular cavity size (P=0.02 and 0.002, respectively). Measured haplotype analyses confirmed the association of alleles at the intron conversion and G5937C polymorphisms with cardiac wall thickness (P=0.02), and alleles at the intron conversion polymorphism with left ventricular cavity size (P=0.04). The polymorphisms contributed to 2.0-3.4% of the variability in these traits. In summary, genetic polymorphisms at the CYP11B2 gene make a small contribution to quantitative variation in echocardiographic measures of heart size. These results point to the importance of analysing the full extent of genetic variation that captures the haplotype structure of a locus in gene association studies.

Cytochrome P-450 CYP11B2↗
PubMed2003

Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period.

OBJECTIVE: Although research suggests that adolescents, particularly girls, may avoid dairy products due to concerns that these foods are 'fattening,' the longitudinal relation between consumption of dairy foods and relative weight status during adolescence has not been explored. Using data from the MIT Growth and Development Study, a longitudinal study designed to assess the metabolic, dietary, and behavioral factors that predict changes in body composition with growth and development in girls during the adolescent period, the current analysis was undertaken to examine the relation of dairy food intake with relative weight status and percentage body fat (%BF). SUBJECTS: A total of 196 nonobese premenarcheal girls 8-12 y old were enrolled between 1990 and 1993. Girls were followed until 4 y postmenarche. MEASUREMENTS: At each annual follow-up visit, data were collected on %BF by BIA, body mass index (BMI) z-score, and dietary intake (assessed by FFQ). The present analysis is limited to the 178 girls who have at least three annual visits and who have valid anthropometric and food frequency data. In all, 1198 individual measurements were analyzed. RESULTS: At study entry, participants had a mean (s.d.) BMI z-score of -0.27 (0.89), a mean (s.d.) %BF of 23.4 (4.7), and obtained 19.9% (9.2) of daily calories from dairy foods. Linear mixed effects modeling indicated no relationship between BMI z-score or %BF and measures of dairy food or calcium consumption. CONCLUSION: Avoidance of dairy foods due to a possible association with relative body weight is not supported by these findings. We find no evidence that dairy food consumption is associated with BMI z-score or %BF during adolescence, but further research specifically designed to address this question is needed.

Adipose Tissue↗
PubMed2002

Particulate matter and polycyclic aromatic hydrocarbon concentrations in indoor and outdoor microenvironments in Boston, Massachusetts.

Estimating personal exposures to air pollution is a crucial component in identifying high-risk populations and determining efficient control strategies. Because of the difficulty of comprehensively measuring personal exposure, data on air pollution patterns in homogenous microenvironments linked with activity data are often used as surrogates. In this study, we focus on strengthening the available information about nonresidential microenvironmental exposures to particulate matter and other combustion pollutants. During the summer of 2000, we measured ultrafine particles, fine particulate matter (PM2.5), and particle-bound polycyclic aromatic hydrocarbons (PAHs) outdoors and in indoor microenvironments in Boston, Massachusetts. In indoor microenvironments averaged across sample days, mean ultrafine particle concentrations ranged from 3800 to 140,000 particles/cm(3), with 7-200 microg/m(3) of PM2.5 and 5-12 ng/m(3) of particle-bound PAH. PM2.5 indoor-outdoor ratios generally exceeded 1 in settings with high levels of human activity, with lower ratios for ultrafine particles. Cooking activities contributed significantly to elevated levels of all three pollutants. Using Linear Mixed Effects models with AR-1 autoregressive correlation structures, 10-min average outdoor concentrations were generally weak predictors of indoor levels, with stronger relationships in an apartment without mechanical ventilation than in air-conditioned nonresidential settings. Although further study would be needed to determine whether these patterns could be generalized beyond the monitored sites, these data support previous findings and enhance our knowledge about nonresidential exposure patterns.

Air Pollutants↗
PubMed2002

Frequency of mouthing behavior in young children.

Young children may be more likely than adults to be exposed to pesticides following a residential application as a result of hand- and object-to-mouth contacts in contaminated areas. However, relatively few studies have specifically evaluated mouthing behavior in children less than 5 years of age. Previously unpublished data collected by the Fred Hutchinson Cancer Research Center (FHCRC) were analyzed to assess the mouthing behavior of 72 children (37 males/35 females). Total mouthing behavior data included the daily frequency of both mouth and tongue contacts with hands, other body parts, surfaces, natural objects, and toys. Eating events were excluded. Children ranged in age from 11 to 60 months. Observations for more than 1 day were available for 78% of the children. The total data set was disaggregated by gender into five age groups (10-20, 20-30, 30-40, 40-50, 50-60 months). Statistical analyses of the data were then undertaken to determine if significant differences existed among the age/gender subgroups in the sample. A mixed effects linear model was used to test the associations among age, gender, and mouthing frequencies. Subjects were treated as random and independent, and intrasubject variability was accounted for with an autocorrelation function. Results indicated that there was no association between mouthing frequency and gender. However, a clear relationship was observed between mouthing frequency and age. Using a tree analysis, two distinct groups could be identified: children < or = 24 and children >24 months of age. Children < or = 24 months exhibited the highest frequency of mouthing behavior with 81+/-7 events/h (mean+/-SE) (n=28 subjects, 69 observations). Children >24 months exhibited the lowest frequency of mouthing behavior with 42+/-4 events/h (n=44 subjects, 117 observations). These results suggest that children are less likely to place objects into their mouths as they age. These changes in mouthing behavior as a child ages should be accounted for when assessing aggregate exposure to pesticides in the residential environment.

Age Factors↗
PubMed2003

Respiratory symptoms and peak expiratory flow in children with asthma in relation to volatile organic compounds in exhaled breath and ambient air.

Indoor volatile organic compounds (VOCs) have been associated with asthma, but there is little epidemiologic work on ambient exposures, and no data on relationships between respiratory health and exhaled breath VOCs, which is a biomarker of VOC exposure. We recruited 26 Hispanic children with mild asthma in a Los Angeles community with high VOC levels near major freeways and trucking routes. Two dropped out, three had invalid peak expiratory flow (PEF) or breath VOC data, leaving 21. Children filled out symptom diaries and performed PEF maneuvers daily, November 1999-January 2000. We aimed to collect breath VOC samples on asthma episode and baseline symptom-free days, but six subjects only gave samples on symptom-free days. We analyzed 106 breath samples by GC-MS. Eight VOCs were quantifiable in >75% of breath samples (benzene, methylene chloride, styrene, tetrachloroethylene, toluene, m,p-xylene, o-xylene, and p-dichlorobenzene). Generalized estimating equation and mixed linear regression models for VOC exposure-response relationships controlled for temperature and respiratory infections. We found marginally positive associations between bothersome or more severe asthma symptoms and same day breath concentrations of benzene [odds ratio (OR) 2.03, 95% confidence interval (CI) 0.80, 5.11] but not other breath VOCs. Ambient petroleum-related VOCs measured on the same person-days as breath VOCs showed notably stronger associations with symptoms, including toluene, m,p-xylene, o-xylene, and benzene (OR 5.93, 95% CI 1.64, 21.4). On breath sample days, symptoms were also associated with 1-h ambient NO(2), OR 8.13 (1.52, 43.4), and SO(2), OR 2.36 (1.16, 4.81). Consistent inverse relationships were found between evening PEF and the same ambient VOCs, NO(2), and SO(2). There were no associations with O(3). Given the high traffic density of the region, stronger associations for ambient than for breath VOCs suggest that ambient VOC measurements were better markers for daily exposure to combustion-related compounds thought to be causally related to acute asthma. Alternatively, the low sample size of symptom responses (15-21 responses per 108 breath samples) may have led to the nonsignificant results for breath VOCs.

Adolescent↗
PubMed2005

Reliability of a semi-quantitative method for dermal exposure assessment (DREAM).

Valid and reliable semi-quantitative dermal exposure assessment methods for epidemiological research and for occupational hygiene practice, applicable for different chemical agents, are practically nonexistent. The aim of this study was to assess the reliability of a recently developed semi-quantitative dermal exposure assessment method (DREAM) by (i) studying inter-observer agreement, (ii) assessing the effect of individual observers on dermal exposure estimates for different tasks, and (iii) comparing inter-observer agreement for ranking of body parts according to their exposure level. Four studies were performed in which a total of 29 observers (mainly occupational hygienists) were asked to fill in DREAM while performing side-by-side observations for different tasks, comprising dermal exposures to liquids, solids, and vapors. Intra-class correlation coefficients ranged from 0.68 to 0.87 for total dermal exposure estimates, indicating good to excellent inter-observer agreement. The effects of individual observers on task estimates were estimated using a linear mixed effect model with logged DREAM estimates as explanatory variable; "task", "company/department", and the interaction of "task" and "company/department" as fixed effects; and "observer" as a random effect. Geometric mean (GM) dermal exposure estimates for different tasks were estimated by taking the exponent of the predicted betas for the tasks. By taking the exponent of the predicted observer's intercept (exp(omega i)), a multiplier (M(O)) was estimated for each observer. The effects of individual observers on task estimates were relatively small, as the maximum predicted mean observers' multiplier was only a factor 2, while predicted GMs of dermal exposure estimates for tasks ranged from 0 to 1226, and none of the predicted individual observers' multipliers differed significantly from 1 (t-test alpha = 0.05). Inter-observer agreement for ranking of dermal exposure of nine body parts was moderate to good, as median values of Spearman correlation coefficients for pairs of observers ranged from 0.29 to 0.93. DREAM provides reproducible results for a broad range of tasks with dermal exposures to liquids, solids, as well as vapors. DREAM appears to offer a useful advance for estimations of dermal exposure both for epidemiological research and for occupational hygiene practice.

Administration, Cutaneous↗
PubMed2006

Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients.

Although major depression (MD) and cardiovascular disease (CVD) have been conclusively linked in the literature, the mechanism associating MD and CVD is yet undetermined. The purpose of this paper is to further investigate a potential mechanism involving nitric oxide (NO) and to examine the effect of the selective serotonin reuptake inhibitor paroxetine on NO production by both platelets and the endothelium. In total, 17 subjects with MD and 12 healthy controls (HCs) with no known history of cardiovascular illness completed the study. Paroxetine was administered to both the MD patients and HCs over an 8-week period, and then medication was discontinued. Blood samples were taken at various times throughout paroxetine treatment and after discontinuation. Plasma NO metabolite (NOx) levels were measured by a chemiluminescence method. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of L-[14C]arginine to L-[(14)C]citrulline. Data were analyzed using t-tests and a linear mixed effects model. Baseline levels of both plasma NOx and platelet NOS activity were significantly lower in subjects with MD compared to HCs. Throughout paroxetine treatment, plasma NOx levels increased in both HCs and MD patients. However, platelet eNOS activity decreased in HCs, while no statistically significant change was evidenced in MD patients. These data suggest that, in MD patients, decreased peripheral production of NO, a potential contributor to increased cardiovascular risk, is modified by administration of the antidepressant paroxetine.

Adult↗
PubMed2006

The neural correlates of social anxiety disorder and response to pharmacotherapy.

This study attempted to define further the neural processing events underlying social anxiety in patients with social anxiety disorder (SAD) and their response to pharmacotherapy. Social anxiety-related changes in regional cerebral blood flow were defined by [15O]H2 positron emission tomography (PET) in medication-free individuals with generalized SAD (gSAD), and age- and sex-matched comparison subjects, and analyzed using a linear mixed effects model. PET studies were again acquired in the gSAD individuals following an 8-week, flexible dose treatment trial of nefazodone. Both script-guided mental imagery of an anxiogenic social situation and a confrontational mental arithmetic task were associated with marked increases in self-rated anxiety in both subject groups. For gSAD subjects, social anxiety induced by guided mental imagery was associated with increased activity in the left postcentral gyrus and lenticulate, and the right inferior frontal and middle temporal gyri. Social anxiety induced by the mental arithmetic task was associated with activation of the medial and left dorsolateral prefrontal cortex, cerebellum, thalamus, insula, and ventral striatum. Both tasks were associated with relative decreases in activity in the right amygdala and the hippocampus. A direct group comparison indicated that comparison subjects exhibited a differing pattern of social anxiety-related neural activations. Nefazodone treatment was associated with marked clinical improvement. Comparison of social anxiety-related neural activations prior to and after nefazodone administration indicated greater activity in the precentral gyrus, insula, midbrain/hypothalamus, and middle frontal and anterior cingulate gyrus prior to treatment, and greater activity in the left middle occipital and bilateral lingual gyri, postcentral gyrus, gyrus rectus, and hippocampus after treatment. The results of an analysis relating neural activity and treatment-related changes in symptom severity indicated differential neural responses associated with states of symptom remission vs partial response. The observed social anxiety-related changes in distributed neural activity are consistent with cognitive models of SAD and adaptive decreases in amygdala activity in response to social anxiogenics, and support the association of altered frontal cortical responses with treatment response.

Adult↗