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At least 883 records · Page 49Linked to original sources
PubMed2006

Identification of a new C28H14 polycyclic aromatic hydrocarbon as a product of supercritical fuel pyrolysis: Tribenzo[cd,ghi,lm]perylene.

Tribenzo[cd,ghi,lm]perylene has been identified as a product of the supercritical pyrolysis of both toluene and Fischer-Tropsch synthetic jet fuel. This identification is based on HPLC/UV/MS data, which show that compound I, eluting immediately after five other C28H14 isomers, is also a C28H14 PAH. The UV spectrum of compound I has features of a benzenoid PAH, of which there are only eight C28H14 isomers. Four of these isomers--benzo[a]coronene, phenanthro[5,4,3,2-efghi]perylene, benzo[cd]naphtho[3,2,1,8-pqra]perylene, and benzo[pqr]naphtho[8,1,2-bcd]perylene--have already been identified as supercritical pyrolysis products by matching their UV spectra with those of respective reference standards. A fifth C28H14 PAH--benzo[ghi]naphtho[8,1,2-bcd]perylene, which does not have a reference standard--has also been recently identified through MS and UV data, use of annellation theory to predict UV spectral characteristics, and length-to-breadth ratio/retention time data. Of the remaining three isomers, bisanthene (IUPAC name phenanthro[1,10,9,8-opqra]perylene) has been determined not to be present in our product mixture, as its UV spectrum does not match that of any of our product PAH. Using annellation theory, we predict the UV spectral characteristics of the two remaining C28H14 benzenoid isomers, for which there are no reference standards (tribenzo[cd,ghi,lm]perylene and naphthaceno[3,4,5,6,7-defghij]naphthacene). Results from this analysis show that the predicted UV spectral features of tribenzo[cd,ghi,lm]perylene match those of compound I--and that those of naphthaceno[3,4,5,6,7-defghij]naphthacene are inconsistent with those of compound I. The length-to-breadth ratio of tribenzo[cd,ghi,lm]perylene also agrees with compound I's HPLC elution behavior. This is the first time that tribenzo[cd,ghi,lm]perylene (IUPAC name phenanthro[2,1,10,9,8,7-pqrstuv]pentaphene) has been identified as a product of fuel pyrolysis or combustion.

Chromatography, High Pressure Liquid↗
PubMed2004

D-dimer testing for deep venous thrombosis: a metaanalysis.

BACKGROUND: The use of D-dimer assays as a rule-out test for deep venous thrombosis (DVT) is controversial. To clarify this issue we performed a systematic review of the relevant literature. METHODS: We identified eligible studies, using MEDLINE entries from February 1995 through October 2003, supplemented by a review of bibliographies of relevant articles. Studies reporting accuracy evaluations comparing D-dimer test results with lower extremity ultrasound or venography in symptomatic patients with suspected acute DVT were selected for review. Two reviewers critically appraised each study independently according to previously established methodologic standards for diagnostic test research. Those studies judged to be of highest quality were designated Level 1. RESULTS: The 23 Level 1 studies reported data on 21 different D-dimer assays. There was wide variation in assay sensitivity, specificity, and negative predictive values, and major differences in methodology of reviewed studies. A multivariate analysis of assay performance, controlling for sample size, DVT prevalence, reference standard, and patient mix, found few differences among the assays in effect on test performance as measured by diagnostic odds ratio. Increasing prevalence of DVT was associated with poorer test performance (P = 0.01), whereas the choice of venography as the reference standard was associated with better test performance (P <0.005). CONCLUSIONS: Explanations for the wide variation in assay performance include differences in biochemical and technical characteristics of the assays, heterogeneity and small size of patient groups, and bias introduced by choice of reference standards. Assay sensitivity and negative predictive value were frequently <90%, uncharacteristic of a good rule-out test. General use of D-dimer assays as a stand-alone test for the diagnosis of DVT is not supported by the literature.

Biomarkers↗
PubMed1993

Colour flow and spectral Doppler imaging after papaverine-induced penile erection in 220 impotent men: study of temporal patterns and the importance of repeated sampling, velocity asymmetry and vascular anomalies.

Of 220 impotent men studied, 52 demonstrated venous leakage, 85 had arterial insufficiency and 65 showed normal vascular response. Persistent diastolic velocity > 7 cm/s diagnosed venous leakage with a sensitivity of 94% and a specificity of 69%, using cavernosography as the reference standard. Using clinical response as the reference standard maximal systolic velocity of 30 cm/s identified normal penile arterial response with a sensitivity of 96% and specificity of 82%. There was a good correlation between penile arterial insufficiency and a strong history of arteriopathy. Time to peak systole > 0.1 s was a reliable predictor of arteriogenic impotence and Pulsatility Index (PI) < 300 was discovered only in patients with either venous leakage or arteriogenic impotence. Peak systolic velocity (Tmax) occurred between 5.2 and 6.5 min after injection, and diastolic velocity was minimal at 9 min with only the normal responders showing reversed diastolic flow. However, 22% had a delayed response (Tmax range 1-18 min). Velocity asymmetry was equally common in the three groups and unilateral sampling would have misdiagnosed 6% of patients studied. Vascular anomalies were seen in 13%, particularly a single feeding artery, dorsal vein flow or collateral arterial flow.

Adult↗
PubMed2005

The true treatment benefit is unpredictable in clinical trials using surrogate outcome measured with diagnostic tests.

BACKGROUND AND OBJECTIVES: Clinical trials increasingly use results of diagnostic tests as surrogate outcomes. Our objective was to answer the following questions: (1) is the parameter measured by the reference standard a valid surrogate? (2) How does the tests accuracy influence the estimate of the treatment benefit on surrogate? (3) Is it possible to correct the measured treatment effect given by results of inaccurate tests? METHODS AND SETTING: We reviewed the literature on asymptomatic deep venous thrombosis (DVT), detected by the reference standard and other imaging techniques, as surrogate for venous thromboembolism. The influence of test inaccuracy on the measurement of treatment benefit was calculated as a function of the patient baseline risk, the treatment effect model, and test performances. RESULTS: We show that: (1) asymptomatic DVT is correlated with clinical outcomes but is yet to be established as a surrogate; (2) inaccurate diagnostic test underestimates the treatment effect on surrogate; (3) the prevalence of the disease, the treatment effect model, and the accuracy of the test and the reference standard used to evaluate it need to be known to correct this underestimation. CONCLUSION: Even when the surrogate end point is valid, without a reliable study of the diagnostic test we cannot quantify the true treatment effect.

Biomarkers↗
PubMed1984

[Standardization of reference points in gynecologic radiotherapy].

It was the intention of the members of the study group to develop a high-accuracy reference point system for remote-controlled afterloading therapy of the uterine and vaginal cancer with high dose rates. This enables comparisons to be drawn between the results obtained in various hospitals. This standardization should be used as a general basis for computer calculation.

Female↗
PubMed1997

Carotid artery volume flow: in vivo measurement with time-domain-processing US.

PURPOSE: To evaluate carotid artery volume-flow measurements with time-domain-processing ultrasonography (US). MATERIALS AND METHODS: Volume-flow measurements were obtained in the carotid arteries of nine swine with time-domain-processing US. Four swine were prepared with a model of an arteriovenous shunt. Flow through the carotid artery was varied by means of a number of physiologic and pharmacologic interventions. The reference standard for volume flow consisted of measurements with transit-time US flowmetry. At a limited number of measurement points, this reference standard was validated against true volume flow measured with timed collection. RESULTS: For flow rates less than 500 mL/min, a linear correlation existed between measurements with time-domain processing and the US flow meter (r2 = .96, P < .001, slope = 1.117). Values above 500 mL/min were less well correlated with the reference standard. True flow was underestimated with both methods, less so with time-domain processing than with US flowmetry (underestimation, 10% versus 21%). Measurements were significantly less reproducible with time-domain processing than with US flowmetry (P < .001). Interobserver variability was negligible. CONCLUSION: Because of operator errors, measurements with time-domain processing should be repeated at least three times to ensure accuracy and may be inaccurate in flow rates over 500 mL/min.

Animals↗
PubMed2002

Development and validation of a PCR-based enzyme-linked immunosorbent assay with urine for use in clinical research settings to detect Trichomonas vaginalis in women.

Trichomonas vaginalis infection is highly prevalent worldwide and is associated with poor birth outcomes and enhanced human immunodeficiency virus transmission. Traditional detection methods rely on microscopic examination of vaginal specimens (wet mount) and culture, which can be insensitive and time-consuming. More than 3,000 women attending two sexually transmitted disease clinics were enrolled in this cross-sectional study to evaluate urine-based PCR for detection of T. vaginalis using a combined reference standard of wet mount and culture from vaginal swab. The prevalence of trichomoniasis in the population was 16.7% (502 of 3,009 women) using the reference standard. PCR with urine combined with agarose gel-based detection was 66.9% sensitive and 98.3% specific compared to the reference standard. Detection of PCR products using an unlabeled enzyme-linked immunosorbent assay (ELISA) improved the sensitivity to 86.4%, but specificity fell to 86.1%. Using a digoxigenin-labeled ELISA for detection of amplified T. vaginalis DNA from urine, the sensitivity and specificity of the PCR improved to 90.8 and 93.4%, respectively, compared to wet mount or culture from vaginal swabs. For clinical research settings in which vaginal specimens are not available and culture conditions are not feasible, urine-based PCR-ELISA may be useful for the detection of trichomoniasis in women.

Adolescent↗
PubMed2000

Quantitative measurements of medical images for pharmaceutical clinical trials: comparison between on-site and off-site assessments.

OBJECTIVE: In pharmaceutical clinical trials, quantitative measurements on medical images are often conducted to confirm drug efficacy. This study aims to compare the quantitative image analysis performance of an off-site core laboratory with the performance of investigators from multiple clinical sites. MATERIALS AND METHODS: In a phase I clinical trial, 25 healthy subjects underwent dynamic brain single-photon emission computed tomography (SPECT) scintigraphy with 123I-Altropane, a cocaine analogue with high affinity and selectivity for dopamine transporter sites in the striatum. In 20 patients examined on-site and off-site, a total of 80 measurements were made to calculate the drug's binding potential. A trained technologist off-site at a central core laboratory and on-site investigators at different clinical sites performed the image analysis. These results were compared with measurements made by a subspecialty radiologist whose assessments were the reference standard. Statistical analysis was performed using multiple regression analysis. RESULTS: Measurements from the central core laboratory (off-site) highly correlated (r = 0.95) with measurements of the reference standard. Measurements from the clinical sites (on-site) grouped together had lower correlation (r = 0.84) with the reference standard. This difference was statistically significant (p < 0.05). CONCLUSION: Training and experience in the specific type of image analysis are critical in obtaining consistent data. Quantitative analysis by dedicated personnel at a core laboratory provides highly reproducible results. The findings support off-site assessment of medical images in pharmaceutical clinical trials.

Adult↗
PubMed2006

A detailed study of thermal decomposition, amalgamation/ atomic absorption spectrophotometry methodology for the quantitative analysis of mercury in fish and hair.

The analytical method for determining the concentration of mercury in fish by thermal decomposition, amalgamation/ atomic absorption spectrophotometry was thoroughly studied. Specific issues addressed were accurate modeling of instrumental response, the use of quartz and nickel boats, carryover effects, software limitations, and troubleshooting. The DMA-80 Direct Mercury Analyzer instrument was calibrated using a total of 22 points, and the resultant curves statistically analyzed. At minimum, second-order polynomials were required to adequately model the data. TORT-2 standard reference material was analyzed in both quartz and nickel boats and found to give equivalent performance in both types of vessels and well within the 95% confidence interval. DOLT-3 standard reference material also yielded values well within the 95% confidence interval, but the DORM-2 standard reference material did not. Carryover effects were found to be minimal with a new catalyst tube but increased with catalyst age. Blanks should be run after the analysis of high mercury content samples; however, when the catalyst has aged, two blanks are required to reduce apparent mercury signals to nominal blank values. Comparable results between thermal decomposition, amalgamation/atomic absorption spectrophotometry and cold-vapor atomic absorption spectrophotometry were demonstrated. The feasibility of using this instrument to analyze hair was also explored and found to be suitable. Software problems and limitations have been noted when attempting to implement a high-throughput methodology. Instrumental drift was found to be minimal when operated over long periods. Blank values can provide important diagnostic indicators.

Animals↗
PubMed2005

Renal artery stenosis evaluated with 3D-Gd-magnetic resonance angiography using transstenotic pressure gradient as the standard of reference. A multireader study.

PURPOSE: To evaluate 3D-Gd-magnetic resonance angiography (MRA) in detecting hemodynamically significant renal artery stenosis (RAS). MATERIAL AND METHODS: Thirty patients evaluated for atherosclerotic RAS by MRA and digital subtraction angiography (DSA) were retrospectively included. Standard of reference for hemodynamically significant RAS was a transstenotic gradient of 15 mmHg. DSA visualized 60 main renal arteries and 9 accessory arteries. Pressure gradient measurement (PGM) was available from 61 arteries. Three radiologists evaluated all examinations independently in a blinded fashion. RESULTS: RAS was present in 26 arteries. On MRA, each reader identified 4 of 9 accessory renal arteries, a detection rate of 44%. The three readers correctly classified 22/25/22 of the 26 vessels with a significant gradient as > or =60% RAS and 31/25/32 of the 35 with no significant gradient as < 60% RAS on MRA. Interobserver agreement was substantial. MRA image quality was adequate for RAS evaluations in all patients. ROC curves indicated that MRA is an adequate method for evaluating RAS. When screening for RAS, a 50% diameter reduction cut-off is better than 60%. RAS with 40-80% diameter reductions accounted for 65% of discrepancies. CONCLUSION: MRA is an adequate method for evaluating RAS limited mainly by poor detection rate for accessory renal arteries.

Aged↗
PubMed2003

Stability of multidose, preserved formulation epoetin alfa in syringes for three and six weeks.

The integrity and biological activity of multidose, preserved formulation epoetin alfa stored in syringes at 2-8 degrees C were studied. Three independent 1.0-mL hubless syringes of epoetin alfa 20,000 units/mL were aseptically prepared and refrigerated for three and six weeks (a total of six syringes). Protein integrity was assayed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and glycoprotein detection. Biological activity was determined through a cell-based proliferation assay. The presence or absence of microbial contamination was observed after a one-week culture. A multidose, preserved formulation of epoetin alfa that was opened only at the time of assay served as the reference standard. SDS-PAGE silver-stained gels and immunoblots demonstrated no evidence of erythropoietin degradation after three and six weeks of storage when compared with the reference standard. In addition, SDS-PAGE, immunoblotting, and direct glycoprotein detection found that protein glycosylation was unaffected by the storage. Student's t test detected no significant difference between stored samples and the reference standard in biological activity (p > 0.05). A culture of epoetin alfa in bacterial and eukaryotic cell growth media showed no evidence of contamination. The results suggest that epoetin alfa can be dispensed to patients in prefilled syringes every four to six weeks to coincide with their peritoneal dialysis schedule. The integrity and biological activity of 20,000 units/mL epoetin alfa in prefilled syringes remain intact after three and six weeks when stored at 2-8 degrees C.

Cell Division↗
PubMed2001

Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

CONTEXT: Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU. OBJECTIVES: To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients. DESIGN AND SETTING: Prospective cohort study testing the Confusion Assessment Method for ICU Patients (CAM-ICU) in the adult medical and coronary ICUs of a US university-based medical center. PARTICIPANTS: A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1, 2000, to July 15, 2000, of whom 96 (86.5%) were evaluable for the development of delirium and 15 (13.5%) were excluded because they remained comatose throughout the investigation. MAIN OUTCOME MEASURES: Occurrence rate of delirium and sensitivity, specificity, and interrater reliability of delirium assessments using the CAM-ICU, made daily by 2 critical care study nurses, compared with assessments by delirium experts using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: A total of 471 daily paired evaluations were completed. Compared with the reference standard for diagnosing delirium, 2 study nurses using the CAM-ICU had sensitivities of 100% and 93%, specificities of 98% and 100%, and high interrater reliability (kappa = 0.96; 95% confidence interval, 0.92-0.99). Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older, 0.99 for those with suspected dementia, or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 (all P<.001). Comparing sensitivity and specificity between patient subgroups according to age, suspected dementia, or severity of illness showed no significant differences. The mean (SD) CAM-ICU administration time was 2 (1) minutes. Reference standard diagnoses of delirium, stupor, and coma occurred in 25.2%, 21.3%, and 28.5% of all observations, respectively. Delirium occurred in 80 (83.3%) patients during their ICU stay for a mean (SD) of 2.4 (1.6) days. Delirium was even present in 39.5% of alert or easily aroused patient observations by the reference standard and persisted in 10.4% of patients at hospital discharge. CONCLUSIONS: Delirium, a complication not currently monitored in the ICU setting, is extremely common in mechanically ventilated patients. The CAM-ICU appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes.

APACHE↗
PubMedDate not supplied

Evaluation of a computerized diagnostic decision support system for patients with pneumonia: study design considerations.

Planning the clinical evaluation of a computerized decision support system requires a strategy that encompasses the different aspects of the clinical problem, the technical difficulties of software and hardware integration and implementation, the behavioral aspects of the targeted users, and the discipline of study design. Although clinical information systems are becoming more widely available, only a few decision support systems have been formally evaluated in clinical environments. Published accounts of difficulties associated with the clinical evaluation of decision support systems remain scarce. The authors report on a variety of behavioral, logistical, technical, clinical, cost, and work flow issues that they had to address when choosing a study design for a clinical trial for the evaluation of an integrated, real-time decision support system for the automatic identification of patients likely to have pneumonia in an emergency department. In the absence of a true gold standard, they show how they created a credible, clinically acceptable, and economical reference standard for the diagnosis of pneumonia, to determine the overall accuracy of the system. For the creation of a reference standard, they describe the importance of recognizing verification bias and avoiding it. Finally, advantages and disadvantages of different study designs are explored with respect to the targeted users and the clinical setting.

Cross-Over Studies↗
PubMed2000

The in vitro percutaneous penetration of chlorpyrifos.

Chlorpyrifos is a widely used organophosphate pesticide. In order to study the pharmacokinetics of the penetration of chlorpyrifos through human skin we measured the percutaneous penetration of chlorpyrifos through human skin using an in vitro flow through apparatus. The chlorpyrifos was applied to the skin as a commercial concentrate or as a reference standard dissolved in ethanol. There was a significant difference (P=0.03) between the rate of penetration from the commercial concentrate (9.0 nmoles cm(-2) h(-1)) and that from the reference standard (4.9 nmoles cm(-2) h(-1)). Each experiment was run for 24 h. The recoveries from experiments where chlorpyrifos was applied to the skin as a commercial concentrate and as a reference standard dissolved in ethanol were, respectively, in total 91 and 87% of the applied dose of which 15 and 10% was recovered from the skin, 56 and 66% was recovered from the surface of the skin and 20 and 11% was recovered from the receptor fluid. There was a significant difference in the recoveries from the skin but there was no significant difference in the recoveries from the surface of the skin. We concluded that the majority of a dermal dose of chlorpyrifos was still present at or in the surface of the skin 24 h after application of a dermal dose. Because chlorpyrifos was recovered from the skin after 24 h, it is possible that the skin could act as a reservoir and release chlorpyrifos over a longer period. We also conclude that the solvent vehicle for chlorpyrifos can affect the rate of penetration of the pesticide.

Administration, Cutaneous↗
PubMed2001

Computed tomography scan versus ventilation-perfusion lung scan in the detection of pulmonary embolism.

This study compared the sensitivity and specificity of computed tomography (CT) scan and ventilation-perfusion (V-P) scan in detecting pulmonary embolism (PE) with pulmonary angiogram (AG) as the reference standard. Following a comprehensive search of the indexed medical literature, CT scan studies related to PE diagnosis were systematically evaluated to select those using AG as the reference standard and meeting specified methodologic criteria. Studies were further grouped by those reporting results for central PE findings only versus central and peripheral PE combined. A composite analysis of data derived from seven selected publications yielded sensitivity and specificity estimates for CT scan in detecting PE, which were statistically compared to the published results of a multi-center study reporting the sensitivity and specificity of the V-P scan with pulmonary AG as the reference standard. The calculated CT scan sensitivity was 77% for central PE only data and 81% for central and peripheral PE combined data, and the CT scan specificity was 91% and 98%, respectively. High-probability V-P scan sensitivity was 41% and specificity 97%; high- and intermediate-probability V-P scans combined yielded sensitivity 83% and specificity 52%. The sensitivity for PE detection was significantly greater for CT scan than for high-probability V-P scan; CT scan sensitivity was equivalent to V-P when high- and intermediate-probability scans were considered together. CT scan specificity for central and peripheral PE combined was equivalent to that of the high-probability V-P scan, but significantly greater than that of high- and intermediate-probability V-P scans considered together. Considering that only a small proportion of patients with suspected PE yield high-probability V-P scan results (which are usually indicative of PE), while as many as one-half of patients may yield intermediate-probability results (which are commonly not useful in PE diagnosis), our results suggest the CT scan may be an appropriate study for use by Emergency Physicians in the clinical evaluation of suspected PE.

Adult↗