Biomedical subjects

B G Leroux

Publications and source records attributed to B G Leroux.

13 recordsLinked to original sources

PubMed1997

Evaluating the validity of probing attachment loss as a surrogate for tooth mortality in a clinical trial on the elderly.

Most periodontal trials are based on the assumption that the superior treatment, as judged by short-term intangible changes in probing attachment levels (the surrogate), is also the treatment most likely to affect tooth mortality. This assumption is valid if: (1) the surrogate is informative about tooth mortality, and (2) the surrogate captures a substantial proportion of the treatment effect on tooth mortality (e.g., > 50% or 75%). The goal of this study was to evaluate whether both conditions were satisfied in a randomized controlled trial (RCT) of elders at high risk for dental diseases. The results suggested that the first condition for a valid surrogate was satisfied: Both one- and two-year changes in probing attachment level were informative about tooth mortality risk. A 1-mm loss measured over a one-year period was associated with a 56% increased tooth mortality risk (relative risk = 1.56; 95% confidence interval, 1.08 to 2.26; p = 0.017); a 1-mm loss measured over a two-year period was associated with a 102% increased risk for tooth mortality (relative risk = 2.02; 95% confidence interval, 1.26 to 3.25; p = 0.004). The second condition necessary for a valid surrogate could not be confirmed in the present trial. With 95% confidence, it was concluded that one-year changes in probing attachment level measurements did not capture a significant proportion of the treatment effect (point estimate, 6%; 95% confidence interval;-38% to 53%). No useful statements could be made regarding the proportion of treatment effect captured by two-year changes, due to the width of the confidence interval (point estimate, 18%; 95% confidence interval;-151% to 140%). It is concluded that (1) the evidence surrounding the one-year change in probing attachment level indicates that it can be ruled out as being anything more than a weak surrogate marker for tooth mortality, and (2) further research is required to study the validity of two-year change in probing attachment level as a surrogate marker. Due to characteristics of the population and the treatments investigated, the generalizability of these findings to other RCTs is questionable.

Aged↗

PubMed1996

A biologically-based dose-response model for developmental toxicology.

The methods currently used to evaluate the risk of developmental defects in humans from exposure to potential toxic agents do not reflect biological processes in extrapolating estimated risks to low doses and from test species to humans. We develop a mathematical model to describe aspects of the dynamic process of organogenesis, based on branching process models of cell kinetics. The biological information that can be incorporated into the model includes timing and rates of dynamic cell processes such as differentiation, migration, growth, and replication. The dose-response models produced can explain patterns of malformation rates as a function of both dose and time of exposure, resulting in improvements in risk assessment and understanding of the underlying mechanistic processes. To illustrate the use of the model, we apply it to the prediction of the effects of methylmercury on brain development in rats.

Abnormalities, Drug-Induced↗

PubMed1996

The estimation of caries prevalence in small areas.

National surveys have been effective for the estimation of caries prevalence in broad regions of the US. However, it is unclear if data from such surveys can be used to estimate prevalences in small areas such as states or counties because of small sample sizes within individual areas. In this study, we applied specialized statistical methods to the estimation of small-area caries measures using data from an oral health survey conducted in the State of Washington. Dental exams to assess caries and the presence of sealants and fluorosis were performed on 2921 third-grade students in 84 public schools selected by a stratified random sample from all 39 counties in the state. Statistical methods for small-area estimation were used to estimate disease and sealant utilization measures for each of the counties. Adjustment was made for covariates measured at the school level, including ethnicity and the proportion of children in the Federally sponsored school lunch program. Substantial variability in disease and sealant utilization between counties was found. The estimated number of decayed and filled surfaces per child was 4.7 (inter-county range, 2.4 to 7.4). The estimated number of surfaces of untreated decay was 1.2 per child overall (range, 0.5 to 3.1). Thirty percent of the children had restorative treatment needs (range, 15 to 54%). The prevalence of sealants on one or more permanent molars was estimated to be 34% (range, 19 to 46%). Overall, only 8% of children showed evidence of fluorosis. The results demonstrate the usefulness of small-area estimation methods for oral health surveys.

Child↗

PubMed1996

The validity of spot urine samples for low-level occupational mercury exposure assessment and relationship to porphyrin and creatinine excretion rates.

Hg and porphyrin levels in single void urine specimens (spot samples) were compared with calculated 24-hr urine levels in 35 (20 [correction of 25] male and 15 female) practicing dentists who had been occupationally exposed to low levels of elemental Hg. The study aimed to: 1) determine the individual variability for Hg and porphyrin concentrations in spot samples over a 24-hr period; 2) test for the presence of diurnal variation in urinary Hg and porphyrin concentrations; and 3) determine the time of day at which a spot sample would give a Hg concentration closest to the 24-hr average concentration. Results confirmed previous reports of a first-order diurnal pattern with a mid-morning peak for Hg concentration (P < .001). A second-order model best described creatinine excretion (P = .0089), with peaks at about 5:00 and 19:00. The use of creatinine adjustment for Hg concentration significantly reduced the intraindividual variation around the diurnal curve. No diurnal patterns were found for any of the porphyrins examined. We recommend that, for small clinical studies using urinary Hg concentration, 24-hr sampling would be ideal, but that for mass screenings and cross-sectional studies, spot samples may be useful because they correlate fairly well with 24-hr averages (creatinine adjusted, r = 0.61; unadjusted, r = 0.74). Because of the existence of diurnal variation, for all cases using serial sampling attention should be paid to time of day.

Adult↗

PubMed1995

Circadian variation in urinary excretion of bone collagen cross-links.

Bone resorption can be evaluated by measuring the urinary excretion of collagen type I cross-linked N telopeptides (NTx). Since it is difficult to obtain (and verify) 24 h urine collections from patients, untimed spot urines are more practical. Such measurements, however, need correction for urine dilution and potentially may vary with collection time since a circadian rhythm in bone metabolism has been reported. This study examined cross-link excretion in urine voids serially collected during a 24 h period from subjects living their normal daily routine (as opposed to a controlled hospital setting). This mimics the situation for walk-in patients visiting a clinician and providing a spot urine. A total of 35 dentists (20 males, 15 females) collected all urine voids separately over a 24 h period. Urines were analyzed for creatinine and NTx. The effects of time of day on the excretion rates of these metabolites (in nmol/h) and on the cross-link:creatinine ratio were assessed. A circadian rhythm was evident in the excretion rate of creatinine with a peak in the late afternoon (18% higher than the 24 h mean, p = 0.0004). The NTx excretion rate peaked in the morning (9% higher than the 24 h mean) but this latter rhythm was not statistically significant (p = 0.31). The NTx:creatinine ratio fell during the day from a high (122% of the 24 h mean) in the early morning to a low in the early evening. This rhythm in the NTx:creatinine ratio in untimed spot urines was statistically significant (p < 0.0001). In conclusion, the NTx:creatinine ratio in spot urines from adult outpatient subjects showed a significant circadian rhythm. Variations in creatinine excretion were the primary cause. Time of day should, therefore, be taken into account when comparing test results of spot urines with normal ranges or with other samples from the same subject.

Adult↗

PubMed1995

Effects of Le Fort I osteotomy on human gingival and pulpal circulation.

The maxillary blood flow during the first 24 h following Le Fort I osteotomy was evaluated by laser Doppler flowmetry. Pulpal blood flow was recorded from two maxillary incisors and gingival blood flow was assessed from a site slightly apical to the interdental papilla of the maxillary central incisors of 12 patients receiving Le Fort I osteotomy, nine control patients receiving mandibular osteotomy, and 10 nonsurgical control subjects without orthodontic appliances. Measurements were made before surgery and at time intervals between 0-8, 8-16, and 16-24 h after surgery. The nonsurgical controls were tested at similar intervals. Gingival and pulpal blood-flow measurements did not change over time in the nonsurgical control group. Presurgical blood-flow values did not differ between the two surgical groups. Following surgery, mean gingival (but not pulpal) blood flow was significantly lower for patients treated with Le Fort I osteotomy than for patients treated with mandibular osteotomy. Follow-up examinations revealed that one patient receiving Le Fort I osteotomy experienced loss of gingiva and bone around both central incisors. This patient had one of the largest reductions in gingival blood flow.

Adult↗

PubMed1994

Within-subject coronal caries distribution patterns: an evaluation of randomness with respect to the midline.

The distribution of caries among homologous surfaces can exhibit three possible patterns: random, aggregated, or regular. In a random caries pattern, caries lesions are randomly distributed among homologous surfaces. An aggregated caries pattern is distinguished by the aggregation of lesions on one side of the mouth or the other to a greater extent than would be expected by chance alone. For a regular caries pattern, the left-right distribution of lesions is more homogenous than would be expected by chance alone. A test statistic based on the left-right distribution of caries lesions among discordant homologous pairs was developed to investigate which of these three caries patterns is present in a representative sample of the adult United States population. The data originated from the National Survey of Oral Health in the US (Employed Adults), 1985-1986. Of the 15,132 subjects studied, 12,776 subjects had 2 or more decayed or filled teeth. (At least 2 carious or filled teeth are required for detection of patterns.) Approximately 50% of these subjects (n = 6,439) had two or more discordant homologous tooth pairs. With these tooth pairs, the hypothesis of a random caries pattern was rejected in favor of an aggregated caries pattern (p < 0.0001). Similar findings were obtained with discordant homologous surface pairs. This aggregation of caries on one side of the mouth or the other may be due to genetic, infectious, and/or environmental factors.

Adolescent↗

PubMed1993

AMESFIT: a microcomputer program for fitting linear-exponential dose-response models in the Ames Salmonella assay.

The Ames Salmonella/microsome assay remains the most widely used microbial test for genotoxicity. In this article, we describe a microcomputer program developed to fit a linear-exponential dose-response model to Ames assay data for established mutagens. The model includes a linear term to describe the mutagenic effects of the test agent at low to moderate doses and an exponential attenuation factor to accommodate downturns at high doses due to cytotoxicity. Quasi-likelihood methods are used to obtain estimates of the unknown model parameters, thereby avoiding the need to fully specify the distribution of the experimental data. This method of estimation also allows for extra-Poisson variation that is characteristic of counts of mutant colonies of bacteria observed in the Ames assay. The particular linear-exponential model used here was developed for use in the analysis of a recent large-scale collaborative trial using the Ames assay sponsored by the International Programme on Chemical Safety. The use of our program is illustrated using sample data sets taken from that collaborative study.

Dose-Response Relationship, Drug↗

PubMed1993

Modeling the Ames Salmonella/microsome assay.

Of the many short-term tests for mutagenicity that have been proposed in recent years, the Ames Salmonella/microsome assay is the single most widely used and most thoroughly validated in vitro test system. This assay uses cells cultured in a soft agar containing a trace amount of histidine to allow growth of auxotrophic bacteria, and is designed to detect reverse mutations from auxotrophic cells to histidine-independent prototrophic cells. In this paper, statistical models that have been proposed for the analysis of Ames test data are reviewed, including those of a mechanistic and empirical nature. An extension to the class of biologically based models derived by Margolin, Kaplan, and Zeiger (1981, Proceedings of the National Academy of Sciences 78, 3779-3783) is proposed by allowing for diffusion of histidine within the plate agar. Quasi-likelihood methods for estimating the model parameters are presented, and applied to 1,120 data sets from a recent collaborative trial sponsored by the International Programme on Chemical Safety.

Animals↗

PubMed1992

Exact likelihood evaluation in a Markov mixture model for time series of seizure counts.

This paper provides an alternative to Albert's (1991), Biometrics 47, 1371-1381) approximation to the E-step when using the EM algorithm for parameter estimation in Markov mixture models. Use of a recursive algorithm of Baum et al. (1970, Annals of Mathematical Statistics 41, 164-171) results in exact evaluation of the likelihood, optimal parameter estimates, and very efficient computation. Applications to time series of seizure counts and fetal movements clearly show the advantages of this exact approach.

Algorithms↗

PubMed1992

Maximum-penalized-likelihood estimation for independent and Markov-dependent mixture models.

This paper concerns the use and implementation of maximum-penalized-likelihood procedures for choosing the number of mixing components and estimating the parameters in independent and Markov-dependent mixture models. Computation of the estimates is achieved via algorithms for the automatic generation of starting values for the EM algorithm. Computation of the information matrix is also discussed. Poisson mixture models are applied to a sequence of counts of movements by a fetal lamb in utero obtained by ultrasound. The resulting estimates are seen to provide plausible mechanisms for the physiological process.

Algorithms↗

PubMedDate not supplied

Sources of variation in the mutagenic potency of complex chemical mixtures based on the Salmonella/microsome assay.

Twenty laboratories worldwide participated in a collaborative trial sponsored by the International Programme on Chemical Safety on the mutagenicity of complex mixtures as expressed in the Salmonella/microsome assay. The U.S. National Institute of Standards and Technology provided homogeneous reference samples of urban air and diesel particles and a coal tar solution to each participating laboratory, along with samples of benzo[a]pyrene and 1-nitropyrene which served as positive controls. Mutagenic potency was characterized by the slope of the initial linear component of the dose-response curve. Analysis of variance revealed significant interlaboratory variation in mutagenic potency, which accounted for 57-96% of the total variance on a logarithmic scale, depending on the sample, strain and activation conditions. Variation among replicate extractions of organic material (required for the air and diesel particles) and among replicate bioassays within the same laboratory was also appreciable. The average potencies for air and diesel particles in laboratories using Soxhlet extracts were not significantly different from those in laboratories using sonication, although there was larger interlaboratory variation for the Soxhlet method. Repeatability (which approximates the coefficient of variation within laboratories) ranged from 18 to 40% for air and diesel particles extracted using sonication, depending on the strain and activation conditions. Repeatability of Soxhlet-extracted air and diesel particles, however, ranged from about 37 to 89% including outliers and from about 11 to 31% excluding outliers. Repeatability of the coal tar sample and the 2 positive controls was in the range 18-34%. Reproducibility (which approximates the coefficient of variation between laboratories) was generally at least twice repeatability, and exceeded 100% for Soxhlet-extracted air and diesel particles, as well as 1-nitropyrene. Reanalysis of the data omitting observations of more than 1500 revertants/plate generally had little effect on these results. Elimination of outlying observations had limited impact, with the exception of Soxhlet-extracted air and diesel particles. In this case, reproducibility of bioassay results was notably improved, due largely to the omission of results for replicate extractions which varied more than 5-fold within one laboratory. Normalization of the log potency slopes for the mixtures by the corresponding slopes for benzo[a]pyrene tended to reduce this variation, although variation was increased after normalization by 1-nitropyrene. Adjustment for the percentage of organic matter extracted from the air and diesel particulate samples had little effect on variation for sonication-extracted particles, whereas variation was reduced for diesel particles and increased for air particles for Soxhlet.

Air Pollutants↗

PubMedDate not supplied

Chlorhexidine swabbing applications under various conditions of use in preventive oral care for persons with disabilities.

A sample of 44 adults with severe disabilities completed a randomized single-blind cross-over study testing chlorhexidine swabbing under various conditions: with/without prior dental prophylaxis, reduced frequency of application (2 vs. 5 times per week), and prolonged use (42 weeks). All subjects received therapeutic doses of 10 mL 0.12% chlorhexidine gluconate (Peridex, Procter & Gamble) and 10 mL 0.05% NaF applied with a Toothette (Sage Products). Clinical effectiveness of chlorhexidine swabbing compared with placebo was previously reported. In the present study, while initial benefits were observed to be independent of dental prophylaxis, significant reductions in periodontal scores were sustained by a combination of dental prophylaxis and swabbing protocol, at reduced frequency of application and over prolonged time. High levels of acceptance and compliance by subjects/caregivers were maintained. Subjects/caregivers reported improvements in dental health as well as in attitude, quality of life, and smile. Chlorhexidine swabbing at maintenance frequency, combined with periodic dental prophylaxis, may offer an effective and pragmatic long-term preventive regimen for persons with disabilities.

Adult↗