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PubMed1986

Estimation of drug absorption rates using a deconvolution method with nonequal sampling times.

A method affording direct estimation of the drug absorption rate from blood level data using arbitrary time intervals has been derived based on the staircase input principle. In the derivation, the drug was assumed to follow linear kinetics where the plasma concentration of the drug after an impulse input is expressed by a multiexponential function. Drug absorption was assumed to occur at a constant rate during each subsequent sampling interval. The absorption rate profiles obtained by the method using several numerical examples were expressed as a set of rectangular pulses. Divergence in the profiles reflected blood sampling measurement errors rather than errors due to the deconvolution. Smoothing of the rate profiles by calculating the mean of the absorption rates between adjacent time intervals gave realistic results. Absorption rate profiles for theophylline obtained by the method using published data gave information on the initiation and termination of the absorption as well as the extent of absorption from the dosage form.

Humans↗
PubMed2006

Circulating tumoral cells lack circadian-rhythm in hospitalized metastasic breast cancer patients.

BACKGROUND: The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in observational studies. OBJECTIVES: Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients. MATERIAL AND METHODS: CTC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers. RESULTS AND DISCUSSION: No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients.

Antineoplastic Agents↗
PubMed1993

Reduction of conjugated dienes in lung transplantation: effect of BN 52021.

Oxygen-derived free radicals have been identified as the mediators of tissue injury during reperfusion in organ transplantation. Lipid peroxidation of cell membrane polyunsaturated fatty acids, generating conjugated dienes (CD), is a toxicity of oxygen-derived free radicals. The CD structure in fatty acyl moieties was measured by high-pressure liquid chromatography in samples of inferior pulmonary venous blood and pulmonary tissue to assess reperfusion injury and oxygen-derived free radical-mediated damage in a canine model of left lung allotransplantation. The cold ischemic preservation interval was 6 hours and the posttransplantation monitoring period was 6 hours. Twenty-eight size- and weight-matched adult male dogs underwent left lung allotransplantation and were randomized to receive pulmonary artery flush of modified Euro-Collins (EC) (40 mL/kg) or University of Wisconsin (UW) (40 mL/kg) solutions alone or with the addition of the platelet-activating factor antagonist BN 52021 (10 mg/kg). When employed, BN 52021 was administered to donors 30 minutes before harvest and recipients 30 minutes before reperfusion. Left and right inferior pulmonary venous blood samples were obtained at baseline before transplantation and at 1, 2, 4, and 6 hours after transplantation; tissue samples were obtained after euthanasia. Serum and tissue CD levels are expressed as mean fraction of the total hydroperoxide sample +/- standard error of the mean. At 6 hours after transplantation, the EC group's (n = 7) CD fraction was 0.28 +/- 0.03, whereas that of the EC + BN 52021 group (n = 7) was 0.12 +/- 0.03 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Canine neutrophil adhesion proteins and Fc-receptors in healthy dogs and dogs with adhesion protein deficiency, as studied by flow cytometry.

Murine monoclonal anti-human antibodies directed against neutrophil adhesion protein receptors CD35, CD18, CD11b, CD11c and the Fc-receptors CD64 (Fc gamma RI), CD32 (FC gamma RII) and CD16 (Fc gamma RIII) were evaluated regarding their ability to bind to the canine homologues. The antibodies against CD35, CD18, CD11b, CD11c and CD16 could be used to evaluate the expression of canine homologues. The routine of using frozen cells and thereby avoiding methodological errors, when samples are stained at different times, was evaluated by comparison of receptor expression in frozen and fresh samples from the same dogs. All receptors were expressed consistently on the cell surface on frozen and fresh neutrophils with the exception of CD16, which showed decreased expression in frozen cells. The expression of CD11c on neutrophils from dogs with canine leucocyte adhesion deficiency (CLAD) was analyzed and there was no difference in receptor expression between CLAD-puppies and healthy controls. CD11b/CD18 expression on neutrophil samples from three parents of CLAD-puppies, i.e. heterozygotes, did not differ from receptor expression in normal controls. Analysis of the Fc-receptor expression on neutrophils from CLAD-puppies showed that the expression of CD16 tended to be decreased in patients compared with controls.

Animals↗
PubMed1987

Analysis of ultratrace lithium and boron by neutron activation and mass-spectrometric measurement of 3He and 4He.

A new technique for analysis of lithium and boron at ultratrace concentrations (less than 10(-8)g g-1) is described. The method consists of mass-spectrometric assay of 3He from decay of tritium produced by thermal-neutron reaction on 6Li, and 4He produced by thermal-neutron reaction on 10B. Two neutron-irradiation facilities were used: the McMaster reactor, which is 235U-enriched and light-water moderated; and a graphite-moderated thermal column attached to the 235U-enriched, heavy-water-moderated core at the National Bureau of Standards (NBS) reactor. In the McMaster irradiations, fast neutrons (greater than 0.2 MeV) induce the reactions 14N(n, 3H)12C, 12C(n, alpha)9Be, 16O(n, alpha)13C, and 14N(n, alpha)11B. These reactions become serious sources of error in samples such as human blood which have very low concentrations of lithium and boron, and high concentrations of nitrogen, carbon and oxygen. In the NBS thermal column, fast-neutron reactions are virtually absent, and only corrections for thermal-neutron capture by deuterium, and thermal-neutron (n, alpha) reactions on oxygen, sulfur, chlorine, potassium, and calcium need to be taken into account. Results are presented for various actual samples including human blood and its components, and some standard biological reference materials, to provide a realistic base for other workers to judge the reliability of the method.

Boron↗
PubMed2003

Does transitional zone pull-through in Hirschsprung's disease imply a poor prognosis?

PURPOSE: Accurate frozen section interpretation of intraoperative biopsies is critical to the success of the Duhamel procedure. Errors during sampling or interpretation may result in an abnormal pull-through. The authors' aim was to determine the incidence and outcome of transitional zone pull-through (TZPT). METHODS: Ninety-six children who underwent a Duhamel procedure between January 1987 and May 2002 were followed up prospectively. The outcome of 18 children with TZPT was compared statistically with that of a cohort of 58 patients with a ganglionic pull-through. RESULTS: The incidence of TZPT was 18.8%. Concordance rate between frozen and paraffin-section analyses was 88.5%. The incidence of enterocolitis (P =.003) and intractable constipation (P =.02) was found to be significantly higher in TZPT. There was no significant difference in continence (P =.34), rectal sensation (P =.35), and control (P =.53). Five (27.8%) TZPT patients required a revisional surgery for failure of conservative management. The incidence of stoma placement and revision was significantly less in the ganglionic group (3.4%, P =.007). CONCLUSIONS: Up to one third of patients with TZPT will require revisional surgery for intractable symptoms. Vigilance is warranted in view of the greater risk of enterocolitis. Continence is not significantly affected.

Cohort Studies↗
PubMed2004

Overvalued ideation as a predictor of fluvoxamine response in patients with obsessive-compulsive disorder.

The presence of overvalued ideation (OVI) in patients with obsessive-compulsive disorder (OCD) has been theoretically linked to poorer treatment outcome. OVI has recently been shown to predict treatment outcome in OCD. The purpose of the present study is to determine whether OVI predicts medication treatment response, controlling for initial symptom severity and measurement error. The sample consisted of 34 outpatients diagnosed with OCD who completed an open-label clinical trial of fluvoxamine of 10 weeks' duration. Clinicians administered the Overvalued Ideas Scale (OVIS) at baseline. Symptom severity was rated at baseline and at the end of week 10 using the Yale-Brown Obsessive-Compulsive Scale. Of those who completed the trial, 68% showed a reliable change in obsessions and 62% showed a reliable change in compulsions. Analysis of variance showed that baseline OVIS predicted outcome for obsessions, but not compulsions. A key limitation was the relatively low number of individuals in the upper quartile on the OVIS, thus reducing the predictive power of the measure in relation to treatment outcome. Future research should examine medication treatment outcome with higher scoring patients.

Adult↗
PubMed2000

Laboratory standardization of a large international clinical trial: the DAIS experience. DAIS Project Group. Diabetes Atherosclerosis Intervention Study.

OBJECTIVE: To implement a quality control program for the standardization and harmonization of lipid and lipoprotein analyses as performed at two core laboratories (St. Paul's Hospital, UBC [Vancouver], and NPHI [Helsinki]) for the Diabetes Atherosclerosis Intervention Study (DAIS). DESIGN AND METHODS: A DAISSOFT computer program was designed to minimize the occurrence of data and sample management errors during the course of the study. Fresh human serum was used for the provision of an accuracy based external quality control program that monitored the analytical performance of lipid testing at these two laboratories. A separate program was designed for monitoring hemoglobin A1c (HbA1c). At the outset of the study, allowable total error goals were established for each analyte. Ongoing performance was monitored using bimonthly blinded challenges of fresh human serum. The two EQA programs routinely monitored the analysis of total cholesterol, calculated LDL-cholesterol, HDL-cholesterol, net triglycerides, apoprotein A-1, apoprotein B, and HbA1c. RESULTS: The EQA precision and accuracy data for the measurement of total cholesterol at the two core laboratories over the last 5 years indicated both laboratories operated with good precision, approximately 1% CV over the time period. The accuracy at both laboratories was similar initially. Part way through the study, the accuracy of the cholesterol method at NHPI tended to drift upward with an operating positive bias (+3%) relative to the Abell Kendall reference method. Triglyceride measurements were the most problematic for the study. By EQA cycle 8, the accuracy of the method at UBC had stabilized and was meeting the accuracy goals of the study. NPHI's method was negatively biased relative to the accuracy base of the DAIS study. In spite of recalibrating their method, NPHI found it difficult to maintain consistent accuracy for the measurement of triglycerides during the study. Both laboratories operated their HDL methods with excellent precision. Accuracy at NHPI was well maintained over the course of the study whereas the accuracy of HDL measurements at UBC was more problematic. There was an inconsistent variation in the accuracy of apoprotein A-1 measurements at both laboratories. In most cases, the bias would be corrected by the time of the next EQA challenge. In the case of apo B, one laboratory was standardized to the CDC while the other laboratory was standardized to IFCC/WHO. The discrepancy between these two accuracy bases was >20%. Recalibration to a common accuracy base rectified the problem. Only minor problems were encountered with the precision and accuracy of the DIAMAT assay for hemoglobin A-1c. The two DAIS core laboratories consistently operated within the 9% total error goals of the study for HbA1c. CONCLUSIONS: Through the use of this program, the two DAIS core laboratories were able to maintain their lipid analyses within the limits of allowable total error that had been established for the study.

Apolipoprotein A-I↗
PubMed1991

Automated phenylthiocarbamyl amino acid analysis of carboxypeptidase/aminopeptidase digests and acid hydrolysates.

A fully automated exopeptidase digestion procedure for the partial determination of N- and C-terminal peptide/protein sequence is described. The digestion of various substrates with aminopeptidase M, carboxypeptidase A, P or Y was accomplished with the Varian 9090 autosampler's robotic automix routines. The released free amino acids, in addition to free amino acids from acid hydrolysates, were derivatized with phenylisothiocyanate in an automated fashion and subsequently chromatographed on a C18 column for separation and quantitation. The advantages of automating this precolumn phenylisothiocyanate derivatization are the virtual elimination of sample manipulation errors and very reproducible data due to the precise control of the reaction conditions both of which, facilitate the interpretation of the exopeptidase reaction kinetic data.

Amino Acids↗
PubMed1985

Cervical dysplasia: cytology class III D and CIN I-II.

Some aspects of class III D-smears (suggesting slight to moderate dysplasia) have been investigated. Results of a cytological follow-up in 481 patients and of the histological findings immediately or during the follow-up in 142 patients are presented. In 112 patients a triple cervical smear approach has been used to determine the rate of false negative smears and errors of sampling. This approach includes the preparation of three slides with cellular material obtained separately from the anterior cervical lip, the posterior lip and from the endocervical canal, using three cotton applicators. To compare the results of cytology with the grade of CIN in different areas of the conization specimens triple cervical smears have been taken preoperatively. Finally 28 patients with a conization following a class III D-smear have been investigated for HPV-induced cell changes which were found in six cases.

Adult↗
PubMed2001

Filtration artifacts caused by overloading membrane filters.

The conventional practice of using 0.45 or 0.40 microm membranes to distinguish between the particulate and dissolved phases in natural waters neglects the importance of colloids. Many of the colloids in natural waters pass through 0.45 or 0.40 microm membranes, but a significant fraction at the upper end of the colloidal particle size range is retained. Membrane clogging during filtration decreases the effective pore size and can cause the retention of increasing amounts of colloids. This filtration artifact can cause serious errors in sampling and in assigning trace metals to various particle size classes. We evaluated the effect of membrane loading for two common membrane types (0.45 microm Millipore Durapore and 0.40 microm Nuclepore) on the retention of colloidal Fe, Al, Mn, and OM in three Connecticut rivers. In addition, we used a 1.0 microm Nuclepore membrane to estimate the amount of colloids in the 0.40-1.0 microm size fraction that are retained by membranes during conventional filtration. All samples were collected with clean techniques, and all filtrations were carried out in a class 100 clean room. A peristaltic pump, set at an initial flow rate of 120 mL/min, was used to pump samples through 47 mm diameter inline Teflon filter holders. Back pressure and flow rate were monitored during filtration, and both are good indicators for the onset of membrane clogging. The results show a consistent correlation between increasing back pressure and decreasing concentration of colloidal Fe and sometimes Al, Mn, and OM in the filtrate for all membrane types. Although the shape of the loading-retention curves varied dramatically by site and by membrane type, the essential relationship between back pressure, flow rate, and filtration artifacts during membrane clogging remained the same.

Artifacts↗
PubMed2003

Interatomic distance measurement in solid-state NMR between a spin- 1/2 and a spin- 5/2 using a universal REAPDOR curve.

A universal curve for the solid-state NMR REAPDOR experiment on an isolated spin-1/2-spin-5/2 pair is proposed that provides a simple means to measure their interatomic distance. REAPDOR data were obtained at three separate REAPDOR experiments using different values of the rotor spinning frequency. All points were fitted simultaneously to the universal formula without a need for full density matrix calculations. The 13C-17O distance of 2.45 A was measured between the C6 carbon and the 17O label in a tyrosine sample. The error of 8% in the dipolar coupling (Dfit = 278 Hz) is well within the 15% theoretical tolerance of this curve.

Journal Article↗
PubMed1998

Comparison of reliability of manual and computer-intensive methods for radiodensity measures of alveolar bone loss.

OBJECTIVE: To compare the reliability of radiodensity measurements made from dental radiographs with manual and a novel computer-intensive methods. METHODS: As part of a prospective study of postmenopausal women, a series of seven vertical bitewing radiographs were taken of 36 patients. One of each set of radiographs was repeated. The original and the corresponding duplicate radiographs were used in this study. Radiographs were digitized at 50 microns spatial resolution and 12-bit gray-scale resolution. For the Manual Method, original and duplicate radiographs were manually cropped to improve image homology, histogram matched and mean pixel gray-scale values determined for an alveolar bone ROI within each image. For the computer-intensive method, images were put into registration with ANALYZE software (Mayo Foundation, Rochester, MINN, USA), cropped automatically, histogram matched and color-coded on the basis of the per cent difference. Alveolar bone ROIs adjacent to clinical crowns and root surfaces whose color code indicated less than a 5% change were sampled. Method error (ME) and the coefficient of variation of method error (CVME) were calculated. RESULTS: With the Manual Method the SD between original and duplicate measures was 95.21 out of 4096 gray scale values; ME = 67.32; CVME = 3.78%. For the computer-intensive method, the corresponding values were 54.74, 38.71, and 2.29%. CONCLUSIONS: The new computer-intensive method resulted in a 40% improvement over the Manual Method in the precision of radiodensity measurements.

Absorptiometry, Photon↗
PubMed2003

Alternate site blood glucose testing: do patients prefer it?

AIMS: To examine patients' perspectives on ease of use and pain with the MediSense alternate site blood glucose testing device (Soft-Sense) compared with their current glucose testing method, and to evaluate the analytical performance of the MediSense device with the laboratory reference method. METHODS: Study participants were shown how to use the Soft-Sense glucose device and asked to perform two tests on their forearm. A capillary sample was collected from their finger and tested on the external port of the Soft-Sense meter and a laboratory method (YSI Glucose Analyser). Finally, one drop of blood was also directly tested from the finger onto the external port. Patients completed a questionnaire comparing ease of use and associated pain of their current testing method with the Soft-Sense meter. RESULTS: Patients preferred the Soft-Sense device to their own for ease of use and for less pain (93% found it easier to use and 96% less painful; P < 0.001). Glucose results correlated closely with the laboratory method (mean absolute percentage bias for the forearm 11.0%, finger 6.0%, and collected capillary sample 5.7%). Error grid analysis showed that all Soft-Sense results were clinically acceptable. CONCLUSIONS: Patients prefer the Soft-Sense alternate site testing device to their existing measuring method. The device accurately measures whole blood glucose.

Adolescent↗
PubMed1978

A new personal sampler for organic vapors.

This paper describes the evaluation of a new personal sampler for organic vapors which is totally different from traditional sampling techniques using pumps and adsorption tubes. Sampling of organic vapors is effected by collection on an adsorption substrate contained within a small passive sampler worn by the worker. The collection element is removed from the sampler and subsequently analyzed for organic vapors. The results are equated with the time-weighted-average concentration of contaminants in air. This new sampling device circumvents inherent errors generally associated with sampling pumps and tubes; e.g., changes in pumping rates and variable pressure drops across adsorption tubes. Applications of the sampler were demonstrated on various concentrations of benzene, methyl isobutyl ketone, isooctane, butyl acetate, methyl chloroform, trichloroethylene, butanol and solvent mixtures. Variables studied included the effects of temperature, charcoal lot, and air velocities. In addition, the occurrence of "breakthrough" and effect of time on sample stability were investigated.

Air Pollutants↗
PubMedDate not supplied

Remembering the past and foreseeing the future while dealing with the present: a comparison of young adult and elderly cohorts on a multitask simulation of occupational activities.

Thirty-five young adult and 38 elderly cybernauts, matched for education, sex, alcohol consumption, and time/day of computer use were compared on a computerized simulation of professional activities of daily living (ADLs). The program quantified performance in terms of speed and accuracy on four major constructs: (1) planning (a 30-item office party script); (2) prospective memory (injections, sleep, phone); (3) working memory (PASAT, D2, and CES analogs); and (4) retrospective memory. Participants had to organize an office party, self inject insulin and go to bed at requisite times of day, do "office work" at unpredictable times of day, and answer the phone that blinked but did not ring (near threshold stimulus). The elderly were markedly and equally impaired on all four constructs (F = 24.3, p < .000). The elderly were also equally and markedly impaired on slave and central executive systems (c.f. Baddeley's model) and on event-based and time-based prospective memory (c.f. McDaniel's model)-findings arguing against a "frontal" model of cognitive decline. This supports Salthouse's concept of a "general factors" decline in normal aging due to diffuse deterioration of the brain. On the other hand, as expected from previous findings, the balance of omissiveness/commissiveness was significantly increased in the elderly sample's error profile. Furthermore, the balance of speed and accuracy was significantly increased in the elderly. This defines limits of the "general factors" model. The elderly also markedly underused a clock icon which had to be clicked on to get the virtual time of day necessary for integrating all the required actions. Prospective memory explained 11% of the aging variance despite partialing out of the three other constructs, making it appear as a golden standard of sensititivity to normal aging-though perhaps provided it be implemented in a distracting, multitask, strategically demanding context.

Activities of Daily Living↗