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Sensitive liquid chromatography-tandem mass spectrometry method for the determination of cefixime in human plasma: application to a pharmacokinetic study.

A sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method was developed to determine cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid) in human plasma. After a simple protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C(8) column interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase consisted of acetonitrile-water-formic acid (40:60:0.5, v/v/v). The analyte and internal standard cefetamet were both detected by use of selected reaction monitoring mode. The method was linear in the concentration range of 0.05-8.0 microg/ml. The lower limit of quantification was 0.05 microg/ml. The intra- and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 12.7%. The accuracy determined at three concentrations (0.05, 0.80 and 7.2 microg/ml for cefixime) was within +/-2.0% in terms of relative error. Each plasma sample was chromatographed within 3.5 min. The method herein described was successfully applied for the evaluation of pharmacokinetic profiles of cefixime capsule in 24 healthy volunteers.

Anti-Bacterial Agents↗

Alcohol outlet density and violence: a geospatial analysis.

AIMS: To examine the relationship between alcohol outlet density and violent crime controlling for neighbourhood sociostructural characteristics and the effects of spatially autocorrelated error. DESIGN: The sample for this ecologic study comprised 188 census tracts from the City of Austin, Texas and 263 tracts from the City of San Antonio, Texas. Data pertaining to neighbourhood social structure, alcohol density and violent crime were collected from archival sources, and analysed using bivariate, multivariate and geospatial analyses. RESULTS: Using ordinary least squares analysis, the neighbourhood sociostructural covariates explained close to 59% of the variability in violent crime rates in Austin and close to 39% in San Antonio. Adding alcohol outlet density in the target and adjacent census tracts improved the explanatory power of both models. Alcohol outlet density in the target census tract remained a significant predictor of violent crime rates in both cities when the effects of autocorrelated error were controlled for. In Austin, the effects of alcohol outlet density in the adjacent census tracts also remained significant. The final model explains 71% of the variance in violent crime in Austin and 56% in San Antonio. CONCLUSIONS: The findings show a clear association between alcohol outlet density and violence, and suggest that the issues of alcohol availability and access are fundamental to the prevention of alcohol-related problems within communities.

Adolescent↗

The power of tests to detect differences between periodontal treatments in published studies.

10 studies comparing periodontal treatment modalities were re-examined to see if they had adequate power to detect true differences. Attachment level (AL) and pocket depth (PD) were the 2 variables assessed. A statistical test's power refers to its probability of detecting a significant sample difference in treatment means, given a predetermined value for alpha (level of significance), delta (a clinically meaningful underlying difference), and the sample size. Studies were included that stratified their data by initial pocket depths, reported sample size, and lasted at least 6 months. Power calculations were done for 173 treatment comparisons, using delta = 0.5 mm and alpha = 0.05. For shallow pockets (1-3 mm), most studies had a strong chance of detecting true differences (median power = 83%). For moderate pockets (4-6 mm), median power dropped to 38%. However, median power dropped to 14% for deep pockets (> 6 mm), with 75% of the tests having less than a 20% chance of detecting a 0.5 mm difference. Many of the modalities reported as "not significantly different" from each other have not had a fair trial, especially for deep pockets. In order to improve a study's power, 4 factors are discussed: the number of compared treatments, the expected noise or random error, the patient sample size, and the average number of sites per patient for each pocket depth category.

Analysis of Variance↗

Electrolyte concentration differences between left and right vitreous humor samples.

Between-eye differences in electrolyte concentrations were studied in 200 medico-legal autopsies using an ion-specific electrode system. Taking the highest of the paired vitreous potassium concentrations, cases < 15 mM/L were classified as biochemically nonputrefied (Cat.1, n = 124), cases 15 to 20 mM/L as early putrefaction (Cat.2, n = 51), and cases > 20 mM/L as biochemically putrefied (Cat.3, n = 25). Mean paired vitreous sodium for all cases (n = 200) was 112 to 173 mM/L (mean 148, standard deviation (SD) = 8.9); between-eye differences were 0 to 8 mM/L (0% to 5.1% of mean), averaging 1.5 mM/L (1%) and with only one case (in Cat.3) outside instrument accuracy (+/- 3 mM/L). Mean paired vitreous chloride for all cases was 73 to 124 mM/L (mean 109, SD = 7.8); between-eye differences were 0 to 9 mM/L (0% to 8.8% of mean), averaging 1.7 mM/L (1.5%) and with 5 of 200 cases outside instrument accuracy (+/- 3 mM/L). Thus between-eye concentration differences of sodium and chloride are tolerable using this methodology. Previous reports of greater variability likely reflect errors introduced by sample manipulation prior to analysis. By contrast, between-eye differences in potassium in Cat.1 cases were 0 to 2.34 mM/L (0% to 21.8% of mean) averaging 0.37 mM/L (3.3%). Significant and erratic between-eye differences in potassium undermine the usefulness of vitreous potassium in estimation of time of death.

Electrolytes↗

Perception of voiceless fricatives by children with a functional articulation disorder.

The two studies presented here examine the relationship between speech perception and speech production errors in children who have a functional articulation disorder. In both experiments, speech perception was assessed with a word identification test, based upon a synthesized continuum of speech stimuli, contrasting the specific phonemes that were associated with production errors in our sample of articulation-disordered subjects. Experiment 1 required subjects to identify words that contrasted the phonemes /s/ and /S/. In this test, adults, normal speaking 5-year-olds, and some articulation-disordered 5-year-olds identified the words seat and sheet appropriately and reliably. However, a subgroup of articulation-disordered children were unable to identify the test stimuli appropriately. Experiment 2 required a second group of subjects to identify words that contrasted the phonemes /s/ and /theta/. Although both adults and normal speaking children responded appropriately to the words sick and thick, in this test, none of the articulation-disordered children was able to identify these words appropriately. It is concluded that, for a subgroup of children who have a functional articulation disorder, production errors may reflect speech perception errors.

Adult↗

The effects of corrective lenses on various behaviors of mentally retarded persons.

A questionnaire was developed to measure changes in certain behaviors at various intervals after correction of refractive errors in a sample of mentally retarded persons. The sample comprised three age groups: 0 to 6 years, 7 to 17, and 18 and above. In each age group, four subgroups were selected--one experimental (new-glasses) group and three control groups. In the group which received new spectacles, changes were recorded in social behaviors, gross and fine motor skills, and reading and writing skills. These changes were most evident in the youngest age group.

Adolescent↗

Visible and near-infrared calibrations for quality assessment of fresh phase I and II mushroom (Agaricus bisporus) compost.

Previous studies have shown that visible and near-infrared spectra (Vis-NIR) of dry and milled compost can be used for generating partial least squares (PLS) calibrations of phase II compost parameters including ammonia, nitrogen dry matter (NDM), dry matter (DM), pH, conductivity, carbon, microbial population, and potential productivity. The objective of this study was to develop robust calibrations for some of the key parameters from the spectra of fresh phase I and II composts. Samples of substrates from six commercial production yards were obtained during winter and summer months of 2000-2004 to monitor changes in quality and were analyzed for the test factors. Vis-NIR reflectance measurements of fresh samples (740) were made over the range of 400-2500 nm. After mathematical pretreatments, PLS calibrations of the key parameters were developed using the NIR (1100-2500 nm) and visible and NIR (400-2500 nm) regions and subsequently validated using an independent sample set of 123 phase I and II samples obtained during 2004-2005. The phase I and II standard errors of laboratory measurements of ammonia, pH, conductivity, DM, NDM, and ash were lower than the standard error of predictions of the same parameters, respectively, by the best NIR or Vis-NIR models. The degree of precision for some of the calibrations, especially ammonia, NDM, and DM, is suitable for composters to monitor changes in quality parameters during production. The laboratory measurement errors for phase I samples were greater than those of the phase II samples, except for ash, due to a higher degree of heterogeneity in the substrate. The calibrations, especially for pH, conductivity, and ash, need to be improved with new sample sets. A major advantage of NIR spectroscopy is the ability to assess substrate quality for a range of target parameters simultaneously, within a few hours of receiving the samples. The main drawbacks are the expensive instrumentation, expertise, and training necessary for operating the spectrometer and a dedicated chemometrician required for maintaining the equations compared to the reference methods.

Agaricus↗

Laboratory error undetectable by customary quality control/quality assurance monitors.

The preanalytical, analytical, and postanalytical rates of laboratory error have not been studied extensively. We evaluated the preanalytical, analytical, and postanalytical components of laboratory error in 438 consecutive samples submitted to a clinical chemistry laboratory for measurement of creatinine concentrations in plasma. We performed red blood cell antigen determinations to establish patient-sample identity, repeated analysis of creatinine in duplicate to detect analytical error, and tracking of patient specimens from receipt by the laboratory to entry of the laboratory result in the patient's information system record. We found a total error rate of 9.36%. A breakdown of the total error rate into its preanalytical, analytical, and postanalytical components revealed error rates of 0.00%, 8.90%, and 0.46%, respectively. These results suggest that preanalytical and postanalytical error, which are not usually detectable by common quality control strategies, are not major sources of laboratory error. Further work is needed to reduce the unacceptably high rate of analytical errors.

Chemistry, Clinical↗

Stature reconstruction from long bones in ancient population samples: an approach to the problem of its reliability.

Stature estimates provided by the application of the anatomical method of Fully and Pineau (1960) to well preserved Neolithic skeletons (39 males and 27 females) from seven different European countries are compared with those drawn from lower-extremity components by means of regression equations commonly used to predict stature of earlier European populations. The analysis of data, carried out with reference both to the sample of origin of the skeletons and to stature classes, suggests that the equations of Pearson (1899) and of Trotter and Gleser for Negroes (1952, 1977) yield very good estimates in female samples, leading to errors below 2 cm in most of the cases. These equations, and those of Olivier et al. (1978), prove useful for stature reconstruction in males too, with the exception of very low (below 154 cm) and very tall (over 179 cm) individuals. Formulae of Breitinger (1938) yield values consistent with those resulting from the anatomical method only within a range including medium-high statures, while the corresponding Bach (1965) formulae for females provide poor approximations. The Trotter and Gleser formulae for Whites (1952) yield very unsatisfactory evaluations, except in specimens taller than 180 cm, and usually overestimate stature both in male and in female skeletons. The results obtained from the long bones by means of alternative approaches to the least-squares regression formulae (Model II regression, and femur/stature ratio) and their efficacy in predicting stature of the samples under study is discussed in the final part of the paper.

Anthropometry↗

[Study on the characteristics and compositions of fine particles left in the solution after decomposition of plant samples].

After decomposition of plant standard reference materials bush twigs and leaves (GBW07602, GBW07603), poplar leaves (GBW07604) and tea (GBW07605) with either dry ashing method or wet digestion method, all kinds of fine particles left in the solution were collected and examined carefully by a scanning electron microscope (SEM), and their chemical composition were investigated by a SEM-affiliated energy-dispersive X-ray spectrometer at the same time. Moreover, the concentrations of some metal elements distributed among four different tea SRM-originated particle fractions extracted following the BCR sequential extraction procedure were determined by AAS and ICP-AES. It was found that decomposition methods have a great influence on the structure of fine particles. When dry ashing method is used, grey-colored, fluffy and porous partices can be produced, whereas fewer white-colored, compact particles can be produced when another method is used. As for chemical composition, all kinds of fine particles are almost the same, with silicon and aluminium as their main constituents, and calcium, iron, potassium, titanium and so on as their minor ones. The elementaI distribution percentages in four different particle fractions in two kinds of plant-originated particles differ from element to element, which can result in severe negative errors when plant samples are decomposed and determined for elemental concentrations.

Camellia sinensis↗

Comparison of four sib-pair linkage methods for analyzing sibships with more than two affecteds: interest of the binomial maximum likelihood approach.

Family samples collected for sib-pair linkage studies usually include some sibships with more than two affecteds (multiplex sibships). Several methods have been proposed to take into account these multiplex sibships, and four of them are discussed in this work. Two methods, which are the most widely used, are based on the number of alleles shared by the sib-pairs constitutive of the multiplex sibship, with the first using the total number of these shared alleles ("all possible pairs" method) and the second considering a weighted number of these alleles (weighted method). The two other approaches considered the sibship as a whole, with in particular a likelihood method based on a binomial distribution of parental alleles among affected offspring. We theoretically show that, in the analysis of sibships with two affecteds, this likelihood method is expected to be more powerful than the classical mean test when a common asymptotic type I error is used. The variation of the sibship informativeness (assessed by the proportion of heterozygous parents) according to the number of affected sibs is investigated under various genetic models. Simulations under the null hypothesis of no linkage indicate that the "all possible pairs" is anticonservative, especially for type I errors < or = 0.001, whereas the weighted method generally provides satisfactory results. The likelihood method shows very consistent results in terms of type I errors, whatever the sample size, and provides power levels similar to those of the other methods. This binomial likelihood approach, which accounts in a natural way for multiplex sibships and provides a simple likelihood-ratio test for linkage involving a single parameter, appears to be a quite interesting alternative to analyze sib-pair studies.

Adult↗

Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36.

UNLABELLED: The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent. The average family size was 11.1 individuals and was composed of 2.7 generations. Recruitment criteria specified that each family contain at least two myopic members. The mean spherical equivalent refractive error in the sample was -3.46D (SD=3.29) and 87% of individuals were myopic. Microsatellite genotyping with 387 markers was performed on 411 individuals. We performed multipoint regression-based linkage analysis for ocular refraction and a log transformation of the trait using the statistical package Merlin-Regress. Empirical genomewide significance levels were estimated through gene-dropping simulations by generating random genotypes at each of the 387 markers in 200 replicates of our pedigrees. Maximum LOD scores of 9.5 for ocular refraction and 8.7 for log-transformed refraction (LTR) were observed at 49.1 cM on chromosome 1p36 between markers D1S552 and D1S1622. The empirical genomewide significance levels were P=0.065 for ocular refraction and P<0.005 for LTR, providing strong evidence for linkage of refraction to this locus. The inter-marker region containing the peak spans 11 Mb and contains approximately 189 genes. CONCLUSION: We found genomewide significant evidence for linkage of refractive error to a novel QTL on chromosome 1p36 in an Ashkenazi Jewish population.

Alleles↗

An evaluation of errors in the determination of blood flow by the indicator fractionation and tissue equilibration (Kety) methods.

In this report, the effects of various errors and plasma time courses of indicator concentration on the accurate determination of cerebral blood flow (F) are theoretically analyzed for the tissue equilibration and the indicator fractionation techniques. For the indicator fractionation technique, the impact of sample timing and tissue assaying errors and of indicator backflux were examined; for the tissue equilibration method, errors in the value of the partition coefficient (lambda), sample timing, and tissue assaying were considered. The recommended ways to decrease the effects of errors in the indicator fractionation technique are to administer the indicator by an intravenous bolus and to sample the tissue about 10 s thereafter. Possible errors in the assessment of F by the tissue equilibration technique are diminished by using an indicator infusion schedule which yields a continuous rise in arterial concentration and by selecting a 30-s experiment duration. Surprisingly, the impact of sample timing errors is greater on the determination of F with the tissue equilibration method than with the indicator fractionation technique. For the chosen plasma time courses, there is always a backflux error in an indicator fractionation estimation of F, and this error increases as the flow rate increases. Thus, provided the sample timing and tissue assay errors are small and the value of lambda is known, the tissue equilibration method is the more accurate of the two. If lambda is unknown, then the indicator fractionation technique should be used. In many cases, the indicator fractionation method will provide as accurate an estimate of F as will the tissue equilibration method.

Animals↗

A comparison of single blood sample and multiple blood sample methods to measure GFR in a pediatric population.

Several single-sample, Cr-51 EDTA based methods of estimating glomerular filtration rate in children have been proposed. The authors retrospectively reviewed our experience in 467 pediatric patients using Tc-99m DTPA and 4 ultrafiltered serum samples drawn 2-4 hours postinjection. The authors used the 2-hour specimens for the single-sample method. Regression analysis of the 2 techniques revealed significant scatter. Mathematically, it was shown that the error of the single-sample method was minimized when the clearance t 1/2 equalled the sampling time x 0.693. This model predicted a 300% error when the t 1/2 was varied to its observed extremes. The observed error of the single-sample method fit this theoretical prediction very well. Analysis of a two-sample method versus the four-sample method showed no improvement in results. In a subset of 18 unfiltered plasma samples, the glomerular filtration rate was falsely low in 12 patients. The authors conclude that multiple blood samples and serum ultrafiltration are required to accurately measure glomerular filtration rate when using Tc-99m DTPA.

Adolescent↗

Incidental sampling of branchial remnants: a potential source of error in fine-needle aspiration of neck lesions-a case report.

Remnants of the branchial apparatus can produce lesions in the head and neck region in later life, often amenable to fine-needle aspiration (FNA) diagnosis. Yet such remnants or rudimentary lesions can remain clinically undetected and can later interfere with the cytologic interpretation of other deep lesions of the neck, as the present case demonstrates. In this case the lesion, which by a subsequent resection turned out to be a neurilemmoma, had been adequately sampled by the FNA, yet the cytologic diagnosis was sidetracked by the presence in the specimen of immature squamous epithelial tissue fragments and other elements (multinucleated histiocytes, calcifications), on the basis of which the diagnosis of an epithelial lesion, likely malignant, was made. The neck surgery and a preceding endoscopic examination of the mouth, pharynx, and larynx did not identify such a lesion, but a detailed microscopic examination of the fibroadipose tissue between the tumor and the peripharyngeal region revealed the presence of epithelial microfragments with morphology partly corresponding to that of the FNA cytology, highly indicative of a branchiogenic lesion in the peripharyngeal region. The basic embryology of the branchial apparatus resulting in such defects is presented, as well as tentative guidelines for recognizing material deriving from accidental sampling of such lesions during FNA investigations of deep-seated masses of the neck. Diagn. Cytopathol. 2000;22:157-160.

Aged↗

Refractive error, IQ and reading ability: a longitudinal study from age seven to 11.

Children from a population sample whose cycloplegic refractive errors included myopia, pre-myopia and hypermetropia were compared on measures of IQ and reading with a group of children without significance refractive errors. At age 11 both those with myopia and with pre-myopia had increased verbal and performance IQ, while those with hypermetropia had slightly reduced verbal and performance IQ, in comparison with the children without refractive errors. The differences in verbal IQ were not attributable simply to earlier differences, but the differences in performance IQ were attributable to earlier differences. No significant differences in reading scores were found at either age. It is concluded that differing abilities of myopic and other children at age 11 are not fully explained by differences in family background or in pre-existing ability.

Child↗

Interpreting age, period and cohort effects in plasma lipids and serum insulin using repeated measures regression analysis: the CARDIA Study.

Observed changes in health-related behaviours and disease risk factors may arise from physiological or environmental changes, or from biases due to sampling or measurement errors. We illustrate problems in the interpretation of such changes with longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Mean plasma cholesterol was 14 mg/dl higher in 27- than in 20-year-old black men cross-sectionally, but longitudinally it declined by 4 mg/dl during the 7 years. To sort out these contradictory assessments of the effect of age/passage of time, we estimated age and period effects under the assumptions that age effects are a smooth function of age independent of period, and that period effects are changes common to persons across all ages. Simple estimates the age effect, such as the cross-sectional age slopes, may be confounded by cohort effects, by interactions of time and age after baseline, or by the occurrence of non-linearities in response after baseline. We note examples of each potential type of bias. The data and background literature support the assumption that cohort effects do not seriously compromise interpretation for these variables in the CARDIA study. Strong secular decreases in plasma cholesterol, apparently due to population-wide dietary change, mask increases with ageing. Age increases in triglycerides are largely explained by increases in body fatness. For these data, we cautiously accept the cross-sectional age slope as an estimate of ageing and the age-matched time trend as an estimate of secular trend.

Adolescent↗

An evaluation of Jochim's PT Scale in the prediction of premature termination from outpatient psychotherapy.

Premature termination from psychotherapy has been a persistent problem to therapists. In an effort to identify potential premature terminators, Jochim (1974) examined the items on the Social History Questionnaire and their capacity to differentiate those patients (N = 103) who terminated treatment prematurely from those who remained. The result was a 23-item instrument that was able to identify accurately 91% of the remainers and 92% of the terminators. The purpose of this research was to determine the generalizability of Jochim's PT scale. Using the recommended cut-off scores, 50% of the Ss were classified inaccurately or unclassifiable. The best cut-off score for this sample produced an error rate of 36.9%.

Adult↗