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PubMedDate not supplied

Accuracy of 3 diagnostic tests for anterior cruciate ligament tears.

CLINICAL QUESTION: In patients presenting with possible rupture of the anterior cruciate ligament (ACL), which diagnostic test can provide an accurate diagnosis during the physical examination? DATA SOURCES: Two reviewers searched MEDLINE (1966 to February 14, 2003) and EMBASE (1980 to February 14, 2003). Articles written in English, French, German, or Dutch were included. The key search terms were knee injuries, knee joint, and knee. These terms were combined with the headings joint instability and anterior cruciate ligament, as well as the text words laxity, instability, cruciate, and effusion. The results of these searches were combined with the subject headings sensitivity and specificity, physical examination, and not (animal not [human and animal]). Additional text words searched were sensitivit*, specificit*, false positive, false negative, accuracy, screening, physical examination, and clinical examination. The reference lists of included articles were examined. STUDY SELECTION: Inclusion criteria consisted of (1) investigation of at least one physical diagnostic test for assessment of ACL ruptures in the knee and (2) the use of a reference standard of arthrotomy, arthroscopy, or magnetic resonance imaging. DATA EXTRACTION: Two independent reviewers extracted data from each included study. The methodologic quality of each test was assessed and recorded on a checklist for the screening of diagnostic tests (www.cochrane.de/cochrane/sadtdoc1.htm). The 3 diagnostic tests validated in this review were the pivot shift test, the anterior drawer test, and the Lachman test. A summary receiver operating characteristic curve was performed for each test, and the sensitivity, specificity, and predictive values were reported. MAIN RESULTS: The search strategy produced 1090 potentially eligible studies, of which 17 studies were selected. One study was included via reference list examination and 2 reports referred to the same study. Thus, 17 studies met the inclusion criteria and were used for this review. For the included studies, the sample size ranged from 32 to 300 patients. As for the age of the subjects, the authors of 4 studies failed to report it. Thus, the average age of patients across 13 of the 17 studies was 28.6 years. Authors of all studies failed to measure the clinical test and reference standard separately and with blinding. In addition, all but two studies had a significant degree of verification bias. Arthrotomy was the lone reference standard in 4 studies whereas arthrotomy/arthroscopy was the reference standard in 5 studies. Arthroscopy alone was the reference standard in 6 studies where only 2 studies used MRI as the reference standard. Authors of 8 studies examined the anterior drawer test and reported sensitivity values ranging from 0.18-0.92 and specificity values ranging from 0.78-0.98. When pooled together using the bivariate random effects model (BREM), the sensitivity value of the 8 studies was 0.2 and the specificity value was 0.88. Authors of 9 studies examined the Lachman test and reported sensitivity values ranging from 0.63-0.93 and specificity values ranging from 0.55-0.99. Pooled together using the BREM, the sensitivity value was 0.86 and the specificity value was 0.91. Lastly, authors of 6 studies examined the pivot shift test and reported sensitivity values ranging from 0.18-0.48 and specificity values ranging from 0.97-0.99. Data for the pivot shift test could not be pooled using the BREM because of the low number of available studies. Predictive values were reported graphically, with the pivot shift test having the highest positive predictive value and the Lachman test having the best negative predictive value. CONCLUSIONS: Based on predictive value statistics, it can be concluded that during the physical examination, a positive result for the pivot shift test is the best for ruling in an ACL rupture, whereas a negative result to the Lachman test is the best for ruling out an ACL rupture. It can also be concluded that, solely using sensitivity and specificity values, the Lachman test is a better overall test at both ruling in and ruling out ACL ruptures. The anterior drawer test appears to be inconclusive for drawing strong conclusions either way.

Journal Article↗
PubMed1999

Proficiency test for screening mammography: results for 117 volunteer Italian radiologists.

OBJECTIVE: To analyse the performance of a large sample of Italian radiologists undergoing a proficiency test for screening mammography. DESIGN: Evaluation of performance indicators according to reference standards determined by a panel of experts (sensitivity (reference standard > or = 80%), recall rate (reference standard < or = 15%)). SETTING: 117 Italian radiologists of varying experience (years of practice 0.5-18, average 5.9; mammograms read 500-51,000, average 13,000), all currently reporting clinical mammography and planning to take part in screening in the near future. RESULTS: Eighty four of 117 (72%) radiologists reached the standard for sensitivity, 88 (75%) reached the standard for recall rate, and only 59 (50%) reached both standards and passed the proficiency test. The probability of passing the test was significantly correlated with mammographic practice (p = 0.015), mammograms read (p = 0.024), and mammograms read/year (p = 0.043). DISCUSSION: The performance of a large sample of Italian radiologists currently reporting clinical mammography was disappointing, indicating the need for proper training of at least 50% of the tested subjects. When implementing organised screening the health authority should set up a proper process for training and accrediting radiologists, and a proficiency test should be part of such a process.

Chi-Square Distribution↗
PubMed1991

Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: I. Without exogenous activation.

There has been an increasing need in genetic toxicology to progress from strictly qualitative tests to more quantitative tests. This, in turn, has increased the need to develop better quality assurance and comparative bioassay methods. In this paper, two laboratories tested 10 Salmonella mutagens in order to determine the usefulness of selected chemicals as potential reference materials to calibrate the Salmonella assay. If variance within a bioassay is sufficiently low and the rankings of the compounds are of acceptable consistency, the chemicals later could be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The results demonstrated that the chosen chemicals (with the possible exception of dimethylcarbamylchloride) provide such consistent results in the Salmonella mutagenicity bioassay that they can be used for semi-quantitative calibration and as possible bioassay controls, special audit chemicals, and potentially as reference standards in comparative bioassay efforts. Reference standards, whether used as audit materials or in comparative bioassays, must be used concurrently with the test substances of interest; used without bias; used in a standardized, highly controlled bioassay; and be tested across an appropriate dose range. The study also shows that when these compounds are used as reference standards much care must be given to the number and spacing of doses if highly reproducible slope values are to be generated. We recommend use of a pilot test to establish a dose range for definitive tests and the placement of doses for the definitive tests within the first half of the linear dose-response curve. For appropriate comparisons, one should replicate the tests using the defined dose range and analyze the results in a non-biased statistical manner.

Calibration↗
PubMed1997

Observer agreement about laryngoscopic assessment of papilloma.

BACKGROUND: Observer bias may confound the assessment of therapies utilized for recurrent respiratory papilloma, a recidivistic fluctuating disease. Any convincing change in a patient's disease must exceed the imprecision of the measuring system. MATERIALS AND METHODS: Videotapes of ten children, who had airway endoscopy for care of laryngeal papilloma, were edited. The videotapes were independently reviewed by six otolaryngologists, of whom five repeated their assessments 5 to 20 weeks later. The 'reference standard' was the operating surgeon's categorization of his patient's videotape. Agreement was calculated by the kappa statistic, the observed proportions of positive and negative agreement, and the proportion categorized as exact opposites, for each of twelve anatomic sites. RESULTS: Moderate agreement was found for both (a) the operative findings versus the later-determined 'reference standard', and (b) the 'reference standard' versus categorizations by other otolaryngologists. Intra-observer agreements were better than inter-observer agreements. Agreement as to whether or not papilloma involved each of twelve sites was within about 20% for the five pediatric otolaryngologists vs the 'reference standard', and within about 10% for the same reviewer. CONCLUSION: Videotapes may add objectivity to the assessment of laryngeal papilloma. For changes to be considered significant, an observer should identify a 10% change in the number of sites involved, or a 30% change in the extent of overall airway obstruction. For different observers, changes would have to be even greater to be meaningful.

Child↗
PubMed2003

Dependence of malaria detection and species diagnosis by microscopy on parasite density.

Giemsa-stained blood smears from each of 2,190 patients from Thai government-operated clinics on the Thailand-Myanmar border were independently examined by the on-duty microscopists at the clinics and by 2-3 research microscopists, each blinded to the clinics' and each other's reports. Using a strictly defined protocol, a consensus reference-standard blood smear interpretation for each sample was produced by the research microscopists. This result was compared with the clinic's diagnostic interpretation for the corresponding sample with respect to detection of parasitemia and diagnosis of infecting species. Reference-standard results reported parasitemia in 13.2% of the samples reported negative by the clinic. Reference-standard results were negative in 24.3% of the samples reported parasite-positive by the clinic. For samples in which both the reference-standard result and the clinic result reported parasitemia, species identification differed for 13.7% of the samples. The likelihood of parasite detection and correct diagnosis at the clinic varied in accordance with the reference-standard estimates of parasite density.

Adolescent↗
PubMed1993

Effect of solvent type on the determination of total iodine in milk powder and human serum by inductively coupled plasma mass spectrometry.

A method for the determination of the total iodine content in milk powder and human serum by inductively coupled plasma mass spectrometry is described. It is shown that the oxidation state of the analyte has a strong impact on the analytical performance. If iodine is present as iodide and nitric acid is used for acidification, the observed ion signal is not stable and samples spiked with iodide yield erroneous recoveries up to 750%. Hence, as the iodine in milk powder is present almost exclusively as iodide, destruction of the sample with nitric acid is not suitable. It was found that such an excessive spike recovery does not occur if ammonia solution instead of nitric acid is used as the diluent. The proposed sample preparation was tested by analysing three reference milk powders, namely Certified Reference Materials 150 and 151 Spiked Skim Milk Powder (from the Community Bureau of Reference) and Standard Reference Material 1549 Non-Fat Milk Powder (from the National Institute of Standards and Technology). Good agreement with the certified values was obtained, indicating that no significant errors are introduced. For human serum, samples treated with nitric acid or with ammonia solution gave results that were not significantly different from each other. Results are given for both a 'second-generation' biological reference material, Freeze-Dried Human Serum (University of Ghent), and for sera from healthy individuals.

Animals↗
PubMed2002

Analysis of clinical brain SPECT data based on anatomic standardization and reference to normal data: an ROC-based comparison of visual, semiquantitative, and voxel-based methods.

UNLABELLED: The technique of anatomic standardization and comparison with normal templates is increasingly used in clinical brain SPECT practice and allows automated, operator-independent volume-of-interest (VOI) or voxel-based analysis of whole-brain data. In 2 distinct clinical populations with severe traumatic brain injury and cognitive impairment, this study compared 3 widely available approaches that use normal templates to evaluate SPECT brain perfusion deficits. METHODS: In total, 74 subjects were studied. These included 14 patients with severe, traumatic brain injury (group 1; 10 males, 4 females; mean age +/- SD, 27.6 +/- 8.2 y) and 15 patients with cognitive impairment (group 2; 7 males, 8 females; mean age, 75.8 +/- 8.6 y). These data were compared with those from, respectively, 25 and 20 age- and sex-adjusted healthy volunteers. All data were analyzed in 4 ways. Three semiquantitative statistical algorithms were used: statistical parametric mapping (SPM) using SPM99, brain registration and analysis of SPECT studies (BRASS) using a voxelwise region-growing technique, and a predefined VOI approach. These results were compared with visual analysis based on consensus reading by 3 experienced nuclear medicine physicians. Receiver operating characteristic (ROC) analysis was performed at various statistical cutoffs. Moreover, as a measure of regional agreement, relative regional agreement between methods was assessed. RESULTS: In both study groups, BRASS voxel-based analysis was most accurate, as defined by the area under the ROC curve (0.97 for group 1 and 0.96 for group 2). VOI assessment was slightly more accurate than visual consensus analysis, whereas SPM showed, overall, a lower area under the ROC curve. SPM analysis was also significantly less sensitive at thresholds corresponding to low false-positive fractions. Regional analysis showed 83%-92% agreement between all methods. CONCLUSION: Under clinical conditions, classification of brain SPECT studies can greatly be aided by anatomic standardization techniques and reference to normal data. Under the investigated circumstances, SPM was found to have a lower sensitivity than VOI or voxelwise region-growing techniques, especially at low false-positive fractions.

Adolescent↗
PubMed1980

Relative potencies of four reference endotoxin standards as measured by the Limulus amoebocyte lysate and USP rabbit pyrogen tests.

Four commonly used reference endotoxin standards, Escherichia coli O113:H10:K0, E. coli O55:B5, Salmonella abortusequi, and Shigella dysenteriae were compared by the USP rabbit pyrogen and the Limulus amoebocyte lysate tests. By the rabbit pyrogen test, S. abortus equi was identified as the most potent endotoxin, followed closely by E. coli O113:H10:K0 and E. coli O55:B5.

Animals↗
PubMed2005

Quantification of trabecular bone structure using magnetic resonance imaging at 3 Tesla--calibration studies using microcomputed tomography as a standard of reference.

The purpose of this study is to use high-resolution magnetic resonance (MR) imaging at 3 Tesla (3T) to quantify trabecular bone structure in vitro using femoral head specimens, and to correlate the calculated structure measures with those that were determined using microcomputed tomography (microCT), the standard of reference. Fifteen cylindrical cores were obtained from fresh femoral heads after total hip arthroplasty. MR images were obtained at 3T using a transmit-receive wrist coil. High-resolution coronal images were acquired using a modified three-dimensional (3D) fast-gradient echo sequence. From these data sets two-dimensional (2D) structural parameters analogous to bone histomorphometry were derived by using both mean intercept length (MIL) methods based on the plate model and the more recent model-assumption free 3D distance-transformation (DT) methods. The parameters measured by the 2D plate model-based MIL method and the DT method included apparent (App). BV/TV (bone volume/total volume), App. Tb.Th (trabecular thickness), App. Tb.Sp (trabecular separation), and App. Tb.N (trabecular number). Identical regions of interest were analyzed in the MR images and the microCT data sets, and similar structure measures were derived. The means and standard deviations of the parameters over all slices were calculated and MR-derived measures were correlated with those derived from the microCT data sets using linear regression analyses. Structure measures were overestimated with MRI, for example, the mean App. BV/TV was 0.45 for MRI and 0.20 for microT, and the slope of the graph was 1.45. App. Tb.Th was overestimated by a factor of 1.9, whereas App. Tb.Sp was underestimated; Tb.N showed the smallest effect. Correlations between the individual parameters were excellent (App. BV/TV, r2 = 0.82; App. Tb.Sp, r2 = 0.84; App. Tb.N, r2 = 0.81), except for App.Tb.Th (r2 = 0.67). The results of this study show that trabecular bone structure measures may be obtained using 3T MR imaging. These measures, although higher than the standard of reference, show a highly significant correlation with true structure measures obtained by microCT.

Aged↗
PubMed2006

A comparison of the accuracy of two minimally invasive breast biopsy methods: a systematic literature review and meta-analysis.

OBJECTIVE: The primary objective was to quantify and compare the accuracy and failure rates of directional vacuum assisted biopsy (DVAB) and core needle biopsy (CNB) when used under stereotactic (ST) guidance to biopsy suspicious breast lesions identified with screening mammography. METHODS: We performed a systematic review of the literature published from January 1996 to July 2004, reporting all-comers populations in Western-style health care systems (i.e., North America, Europe, Australia or New Zealand), referred after screening mammography for breast biopsy using DVAB or CNB under ST guidance. Meta-analyses were conducted for DVAB and CNB, using open surgical biopsy and/or long-term clinical and/or mammogram follow-up as the diagnostic reference standard. The main outcomes of interest were those of greatest clinical relevance, i.e., miss rates and underestimation rates for malignancy. Also, technical failure rate and non-diagnostic rate were assessed for each biopsy method. RESULTS: Thirty-five studies qualified for the review. There were 12 studies with a DVAB group (n=5,119 patients), and 25 studies with a CNB group (n=6,236). There were no studies including both a DVAB and a CNB group, thus precluding any direct, within-study comparisons of accuracy. Overall agreement rate between DVAB and the reference standard was 97.3%, and between CNB and the reference standard, 93.5%. The frequency of technical failures with CNB was slightly higher than DVAB (5.7 vs. 1.5%), as was the frequency of non-diagnostic samples (2.1 vs. 0%). Of the non-diagnostic CNB samples, 23% were subsequently found to be malignant on reference standard. In multivariate analyses using four covariates (procedure type, geographic location, reference standard, and patient position), there were no significant predictors of agreement rates, but some variables were significant predictors of miss rates. For benign to malignant upgrades, study location was a significant predictor, with more upgrades in non-NA locations. For atypia to malignant upgrades, the type of procedure was a significant predictor, with more underestimations in CNB studies. CONCLUSION: The best available evidence suggests that, in screening populations referred for minimally invasive breast biopsy biopsy requiring ST guidance, DVAB may provide lower miss and underestimation rates for clinically relevant diagnoses than does CNB.

Biopsy↗
PubMed1985

Turbidimetric method for quantifying serum inhibition of Limulus amoebocyte lysate.

This study describes a method to quantify the inhibition of lipopolysaccharide (LPS) activity by serum with a turbidimetric Limulus amoebocyte lysate assay. Assays were performed in multiwell microplates, and turbidity was measured as the optical density at 380 nm with a microplate spectrophotometer. LPS potency was measured as the 50% maximal Limulus amoebocyte response (LR50) of LPS diluted with saline. By comparing LR50s in saline, LPSs from various species of bacteria were standardized against the U.S. Reference Standard Endotoxin, lot EC-5. The potency of Escherichia coli O113 and O18 and Serratia marcescens LPSs was found to be equal to that of the reference standard EC-5, whereas LPSs from two salmonella species were half as potent. The least potent LPSs tested, obtained from Klebsiella pneumoniae and E. coli rough mutant J5, were 5- and 10-fold less potent, respectively, than EC-5. As a measure of inhibition, the LR50 of LPS in serum was compared to the LR50 of LPS in saline. Serum inhibited the potency of LPS 103- to 6,400-fold compared with saline. A positive correlation was found between standardized potency in saline and serum inhibition of the various LPSs tested. Thus, LPSs from E. coli O113, O18, and EC-5 and S. marcescens, which exhibited the highest potency in saline, were inhibited the most by serum. Likewise, E. coli J5 and K. pneumoniae LPSs, which were the least potent tested, were the least inhibited. The degree of inhibition of all types of LPS tested increased with increasing serum concentration.

Blood↗
PubMed2003

[Measurement of the AT and the CCD angle of macerated cadaver femora: a comparative study between CT and MRI measurements].

PURPOSE: To compare measurements of the real AT (femoral antetorsion) and CCD (caput-collum-diaphysis) angle by computed tomography (CT) and magnetic resonance imaging (MRI) of hip specimen using direct measurements as reference standard, and to show that measurement by MRI can replace CT measurements and may help avoiding X-ray exposition. MATERIALS AND METHODS: CT and MRI measurements were obtained on 25 in water-arrested macerated human femora. Postprocessing was done by 4 independent readers on a workstation using a dedicated 3D-software. Direct measurements of the real AT and the CCD angle were used as reference standard. The analysis included Student's t test for paired values, interobserver variability using intra-class correlation coefficients (ICC), maximum and middle divergence of the angles, and Bland-Altman plots. RESULTS: For determining AT and the CCD angle with CT and MRI, good correlation was found between the 4 readers and with measurements using the reference standard. ICCs were 0.97 and 0.90 for measuring AT and CCD angle with CT, and 0.95 and 0.71 for measurements with MRI, respectively. Mean divergence between CT measurements and those of the reference standard was 0.8 degrees for AT and 0.7 degrees for the CCD-angle. Mean divergence between MRI measurements and those of the reference standard was 0.3 degrees for AT and -0.4 degrees for the CCD-angle. Mean divergences between CT and MRI measurements of AT and CCD-angle were 0.5 degrees. Neither systematic errors nor dependences on the qualitative size of the reference data were evident in the divergences of measurements. CONCLUSION: Measurements of the real AT and CCD angle by CT and MR imaging revealed a good correlation with direct measurements of the femoral specimen and consequently can be recommended for clinical use. MRI measurements can replace CT measurements, avoiding X-ray exposure especially in young patients undergoing preoperative evaluation for hip dysplasia.

Bone Malalignment↗
PubMed1998

Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation.

OBJECTIVE: To construct an adjusted nomogram for the echocardiographic screening of aortic root diameter in children with possible Marfan disease. DESIGN: In 91 children (42 boys, 49 girls, age range 3.2 to 18.4 years) undergoing Marfan screening from 1983 until 1996, the diagnosis Marfan syndrome and any other aortic pathology was definitely ruled out. These served as a control population to set appropriate reference standards. RESULTS: Compared with a standard Dutch reference population, body surface area of the control subjects (mean (SD)) was above the 50th centile (boys 0.09 (0.20) m2, range -0.28 to 0.69 m2; girls 0.09 (0.17) m2, range -0.17 to 0.69 m2). Echocardiographically determined aortic root diameter and body surface area showed a linear relation and a greater variability of aortic root diameter in these relatively tall subjects (n = 91, R2 = 0.62) than in the standard nomogram (n = 56, R2 = 0.93). In 24% of cases (n = 22), the aortic root exceeded the upper limit of normal in the standard nomogram, by 2.2 (2.0) mm. An adjusted nomogram was constructed with a higher upper limit. CONCLUSIONS: A Marfan screening population differs from the unselected population in body surface area and aortic root size variability. An adjusted nomogram should therefore be used to detect a truly enlarged aortic root.

Adolescent↗
PubMed1991

Growth and milk intake of exclusively breast-fed Myanmar infants.

Twenty-nine exclusively breast-fed infants from moderate and low socio-economic groups were followed-up from birth to 6 months of age. Breast milk intake and body weight of the infants were measured at monthly intervals and morbidity recorded. It is interesting to note that although the mean birth weight of 2.76 kg was only 85 per cent of the NCHS reference standard, catch-up growth occurred whereby the exclusively breast-fed infants attained 94 per cent and 101 per cent of the reference standard at 1 and 2 months of age respectively. At 3 months of age, the mean weight of the infants was 99 per cent of the reference standard and then the growth curve began to falter between 4 and 5 months of age, from 97 per cent at 4 months to 93 per cent of the reference standard at 5 months, the mean weight increment (kg/month) between 4 and 5 months being (less than -1 SD) of the reference value. On the other hand, milk intake of these infants increased from 453 g/d at 1 month to 621 g/d at 4 months reaching a value of 655 g/d at 5 months. It was also observed that the morbidity pattern did not seem to differ, especially at 3-4 months and 4-5 months. The faltering of growth between 4 and 5 months of age was probably due to the fact that the increase in breast milk intake was not sufficient to meet the increase in nutritional requirements needed for the growth of these infants after the age of 4 months.

Birth Weight↗
PubMed2005

Diagnostic value of sonography in patients with suspected carpal tunnel syndrome: a prospective study.

OBJECTIVE: To determine the diagnostic value of sonography in patients with suspected carpal tunnel syndrome (CTS). METHODS: We conducted a prospective study of 110 wrists in 74 consecutive patients with suspected CTS who had been referred to a tertiary care center. We determined the largest cross-sectional area of the median nerve at the carpal tunnel. Because of the lack of a universally accepted reference standard, we first examined the association of sonography with nerve conduction. Then, we compared sonography with a reference standard based on the combination of nerve conduction studies and signs and symptoms. Sonography and reference standard tests were performed independently and interpreted under blinded conditions. Based on a fitted receiver operating characteristic curve, we estimated likelihood ratios (LRs) and posttest probabilities for different cutoffs. RESULTS: There was a high concordance between sonography and nerve conduction. Based on the combined reference standard, a cutoff of 10 mm(2) resulted in approximately equal sensitivity and specificity, but only moderate LRs. A cutoff of <8 mm(2) had satisfactory power to rule out CTS: the fitted-negative LR was 0.13. Conversely, a cutoff of > or =12 mm(2) had excellent power to rule in CTS, with a fitted-positive LR of 19.9. For nerves > or =12 mm(2) and a pretest probability of 70% expected in patients with suspected CTS in tertiary care, we found a posttest probability of CTS of 98%. CONCLUSION: Depending on setting and purpose, different cutoff values for the largest cross-sectional area may be used to accurately rule in or rule out CTS. Using sonography as a first-line test may cost-effectively reduce the number of nerve conduction studies in patients with suspected CTS. A large-scale, randomized controlled trial is required to determine the effects of sonography on clinical outcomes, the number of nerve conduction studies performed, and the total cost.

Adult↗
PubMed2006

Calibration of migration times of variable salinity samples with internal standards in capillary electrophoresis.

A practical approach is presented for identifying the analyte peaks stacked by transient ITP (TITP) in samples of uncontrolled salinity. For TITP with chloride ions acting as the leading electrolyte, the effect of matrix chloride of an unknown concentration was calibrated using multiple internal standards to predict the migration times of weakly acidic anionic analytes behaving as strong electrolytes to an accuracy of over 99.9%. The calibration equations for the migration time of an analyte are given as a function of the migration times of internal standards using the mobilities of the relevant ions as parameters. The effects of matrix chloride and various separation conditions such as the temperature, plug length, ionic strength, and pH of the BGE were completely eliminated from the calibration equations. In addition, the actual mobilities, determined for a standard saline sample under the working conditions, were used, and thus, there was no need to conduct supplementary experiments to determine the absolute mobilities at infinite dilution. The internal standards were dyes, which were easily identified in an auxiliary channel monitoring the absorbance at a longer wavelength. For five standard saline matrices containing 100-300 mM NaCl at intervals of 50 mM, the mean absolute error (MAE) in migration times calibrated with two internal standards was 0.4 s (n=5x13). For an electropherogram of a real standard reference urine sample, peaks of spiked analytes were identified with an MAE of 0.9 s (n=13) without conductivity normalizing or desalting of the sample.

Calibration↗
PubMed1990

Outlier detection in bioavailability/bioequivalence studies.

This paper concerns techniques for detection of a potential outlier or extreme observation in a bioavailability/bioequivalence study. A bioavailability analysis that includes possible outlying values may affect the decision on bioequivalence. We consider a general crossover model that takes into account period and formulation effects. We derive two test procedures, the likelihood distance and the estimates distance, to detect potential outliers. We show that the two procedures relate to a chi-square distribution with three degrees of freedom. The main purpose of this paper is to exhibit and discuss these two general approaches of outliers detection in the context of a bioavailability/bioequivalence study. To illustrate these approaches, we use data from three-way crossover experiment in the pharmaceutical industry that concerned the comparison of the bioavailability of two test formulations and a standard (reference) formulation of a drug. This example demonstrates the influence of an outlying value in the study of bioequivalence.

Analysis of Variance↗
PubMed2000

Determination of blood folate using acid extraction and internally standardized gas chromatography-mass spectrometry detection.

Whole blood folate level is a superior indicator of folate nutritional status than serum/plasma level. Problems with and lack of confidence in results of current whole blood folate assays have limited its popularity for assessing folate nutritional status. Here, an acid extraction GCMS detection method that measures total folate whole blood is presented. Folates are released from the matrix of whole blood and cleaved to para-aminobenzoic acid (pABA) by acid hydrolysis in the presence of [(13)C(6)]pABA as internal standard (IS). The hydrolysate is passed over a C18 resin to remove heme. The pABA isotopomers are ethyl esterified, isolated on C18 resin, and trifluoroacetylated. Following normal-phase HPLC separation, the isotopomers are silylated to their tBDMS derivatives. The abundance of these derivatives are measured at m/z 324 for [(13)C(6)]pABA as IS and m/z 318 for pABA from whole blood folate. Our method uses readily available chemicals and our results agree well with those using Lactobacillus casei, the current gold standard reference assay. The presence of folate analogs (methotrexate) or antibacterials (sulfonamines) does not affect our method. This feature makes it useful in monitoring folate status of patients undergoing chemotherapy. Before using our method, pABA supplements must be discontinued for a few days.

Acids↗