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Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR).

Arterial spin labeling (ASL) permits quantification of tissue perfusion without the use of MR contrast agents. With standard ASL techniques such as flow-sensitive alternating inversion recovery (FAIR) the signal from arterial blood is measured at a fixed inversion delay after magnetic labeling. As no image information is sampled during this delay, FAIR measurements are inefficient and time-consuming. In this work the FAIR preparation was combined with a Look-Locker acquisition to sample not one but a series of images after each labeling pulse. This new method allows monitoring of the temporal dynamics of blood inflow. To quantify perfusion, a theoretical model for the signal dynamics during the Look-Locker readout was developed and applied. Also, the imaging parameters of the new ITS-FAIR technique were optimized using an expression for the variance of the calculated perfusion. For the given scanner hardware the parameters were: temporal resolution 100 ms, 23 images, flip-angle 25.4 degrees. In a normal volunteer experiment with these parameters an average perfusion value of 48.2 +/- 12.1 ml/100 g/min was measured in the brain. With the ability to obtain ITS-FAIR time series with high temporal resolution arterial transit times in the range of -138 - 1054 ms were measured, where nonphysical negative values were found in voxels containing large vessels.

Adult↗

Optimum allocation of samples in strata-matching case-control studies when cost per sample differs from stratum to stratum.

We investigate the allocation of samples over strata in case-control studies with consideration of sampling costs. We consider two situations, typical of strata-matched case-control studies. Subject to a fixed total cost we derived optimum allocations that maximize the asymptotic efficiency of Cochran's test, that is, minimize the variance of the maximum likelihood estimator of the common odds ratio when the common odds ratio is one. Our results show that the standard design with equal numbers of cases and controls in each stratum is inefficient when costs per control differ greatly from stratum to stratum. We show that the optimum design suggested in this paper is robust for values of the odds ratio common in epidemiologic studies.

Case-Control Studies↗

Measurement of interproton, nuclear spin dipolar couplings in liquid crystalline samples by combining variable angle sample spinning, isotope dilution, and deuterium decoupling

The proton NMR spectra of liquid crystalline samples can be simplified by selective, partial deuteration followed by deuterium decoupling. This leaves strong peaks from the protons at the undeuterated sites, but also weak resonances from the coupling of these protons to those at low abundance (2% in the present case) at the deuterated sites. The weak resonances can be separated from the strong by recording spectra while spinning the sample at a series of angles to the magnetic field. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Prediction of two-sample (99m)Tc-diethylene triamine pentaacetic acid plasma clearance from single-sample method.

OBJECTIVES: To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). METHODS: Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. RESULTS: Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1.73 m2, the diagnostic sensitivity of a cut off value of aGFR = 45 ml/min/1.73 m2 was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM. CONCLUSION: When GFR > or =30 ml/min/1.73 m2, tGFR can be predicted from sGFR, which will simplify the reference GFR measurement in clinical trials. sGFR becomes widely scattered when tGFR is less than 30 ml/min/1.73 m2. To obtain reliable reference GFR values, it is recommended that DPSM be used in clinical trials when aGFR is less than 45 ml/min/1.73 m2.

Algorithms↗

Freon (CHF3)-assisted atomization for the determination of titanium using ultrasonic slurry sampling-graphite furnace atomic absorption spectrometry (USS-GFAAS): a simple and advantageous method for solid samples.

A simple and advantageous method for the determination of titanium using graphite furnace atomic absorption spectrometry with slurry sampling has been developed. Titanium is one of the refractory elements that form thermally stable carbides in the graphite tube, which leads to severe memory effects. Trifluoromethane (Freon-23) was applied in the purge gas during the atomization step or alternatively just prior to the atomization to successfully eliminate the problems of carbide formation and increase the lifetime of the furnace tube which could be used for more than 600 heating cycles. A flow rate of 40 mL min(-1) (5% of Freon in argon) was used to obtain symmetrical peaks with no tailing. However, when the gas flow rate was too high (250 mL min(-1)) the peak-tailing and memory effects reappeared. Ti was determined in various materials covering a wide range of concentrations, from 2.8 microg g(-1) to 12% (m/m) Ti. The accuracy of the method was confirmed by analyzing certified reference materials (CRMs) or by comparing the results with those obtained using inductively coupled plasma-atomic emission spectrometry (ICP-AES) after decomposition of the samples. The materials analyzed were soil, plant, human hair, coal, urban particulate matters, toothpaste, and powdered paint.

Journal Article↗

Orthogonal signal correction applied to the classification of wine and molasses vinegar samples by near-infrared spectroscopy. Feasibility study for the detection and quantification of adulterated vinegar samples.

The most common fraudulent practice in the vinegar industry is the addition of alcohol of different origins to the base wine used to produce wine vinegar with the objective of reducing manufacturing costs. The mixture is then sold commercially as genuine wine vinegar, thus constituting a fraud to consumers and an unfair practice with respect to the rest of the vinegar sector. A method based on near-infrared spectroscopy has been developed to discriminate between white wine vinegar and alcohol or molasses vinegar. Orthogonal signal correction (OSC) was applied to a set of 96 vinegar NIR spectra from both original and artificial blends made in the laboratory, to remove information unrelated to a specific response. The specific response used to correct the spectra was the extent of adulteration of the vinegar samples. Both raw and corrected NIR spectra were used to develop separate classification models using the potential functions method as a class-modeling technique. The previous models were compared to evaluate the suitability of near-infrared spectroscopy as a rapid method for discrimination between vinegar origin. The transformation of vinegar NIR spectra by means of an orthogonal signal-correction method resulted in notable improvement of the specificity of the constructed classification models. The same orthogonal correction approach was also used to perform a calibration model able to detect and quantify the amount of exogenous alcohol added to the commercial product. This regression model can be used to quantify the extent of adulteration of new vinegar samples.

Acetic Acid↗

A capillary electrophoresis chip with hydrodynamic sample injection for measurements from a continuous sample flow.

A microchip-based capillary electrophoresis device supported by a microfluidic network made of poly(dimethylsiloxane), used for measuring target analytes from a continuous sample flow, is presented. The microsystem was fabricated by means of replica molding in combination with standard microfabrication technologies, resulting in microfluidic components and an electrochemical detector. A new hydrodynamic sample injection procedure is introduced, and the maximum number of consecutive measurements that can be made with a poly(dimethylsiloxane) capillary electrophoresis chip with amperometric detection is investigated with respect to reproducibility. The device features a high degree of functional integration, so the benefits associated with miniaturized analysis systems apply to it.

Biosensing Techniques↗

Direct solid sample analysis of geological samples with SS-GF-AAS and use of 3D calibration.

These results from direct solid-sample trace-element analysis, with 3D calibration, follow those of earlier publications. Cd, Cr, Cu, Ni, Pb, and Zn have been determined in complex inorganic powder samples, e.g. sediments, soils, rocks, and minerals. The measurements were performed with two SS-GF-AAS spectrometers which differ in the type of graphite furnace (transverse and longitudinal tube) and the background-correction technique (with and without the Zeeman system). The performance of the 3D calibration method was optimized by systematic investigation and the 2D- and 3D calibration techniques were compared. Another feature is the determination of confidence limits of the 3D calibration. This calibration error was calculated by the statistical bootstrap method. The results of calibration experiments and the precision and accuracy of the determination of trace elements in CRMs show that 3D calibration becomes increasingly essential as the refractory character of the analyte increases. Although there are large differences between the state of development and technical performance of the instruments used, 3D-calibration works with both SS-GF-AAS spectrometers.

Journal Article↗

Use of saliva and capillary blood samples as substitutes for venous blood sampling in pharmacokinetic investigations of artemisinin.

OBJECTIVES: Artemisinin concentrations in venous plasma, capillary plasma and saliva were compared. METHODS: Eighteen Vietnamese adults with uncomplicated falciparum malaria were treated with artemisinin. Saliva, capillary and venous plasma were sampled and analysed for artemisinin using high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). RESULTS: Artemisinin capillary plasma concentrations were highly correlated to its venous plasma levels (correlation coefficient r = 0.92). Capillary/venous concentration ratios were significantly higher than unity at 30 min and 60 min after drug intake, indicating an arterial-venous concentration difference. Artemisinin unbound fraction in plasma averaged 0.14 (SD = 0.03) and was independent of drug concentration (114-1001 ng/ml). Artemisinin concentrations in saliva were comparable to its unbound levels in plasma. Saliva levels were more highly correlated to unbound capillary plasma (r = 0.85) than to unbound venous plasma concentrations (r = 0.77). No statistically significant differences were found between the saliva, unbound venous and unbound capillary area under the curve (AUC) values. CONCLUSIONS: Capillary plasma or saliva may replace venous plasma in pharmacokinetic investigations of artemisinin. Due to the ease of collection and handling, saliva sampling can be a simple approach in field studies of artemisinin, although the lower saliva concentrations require more sensitive analytical methods.

Adolescent↗

Discrepancies in bacterial recovery from dental unit water samples on R2A medium and a commercial sampling device.

Monitoring the number of bacterial colony-forming units is an important step in assuring compliance with the recommendation that water from dental units contain <200 CFU mL(-1). Media that have been used for this purpose include R2A, a standard plate counting medium for water samples, and the Millipore HPC Sampler device, designed to facilitate sampling in dental offices. Discrepancies between the two media have been observed. This study tested the hypothesis that differences in counts on the two media were due to the failure of some bacteria to grow on the HPC sampler or to grow at less efficiency than on R2A. Of four different bacterial colony phenotypes tested in three independent experimental trials, one phenotype did not grow on the HPC device, and another grew inconsistently and at lower efficiency. These results confirmed the hypothesis. From these findings, users of the HPC sampler should be aware that microbial undercounts may occur.

Bacteria↗

Isotope dilution ammonia chemical ionization mass fragmentographic analysis of urinary 3-O-methylated catecholamine metabolites. Rapid sample clean-up by derivatization and extraction of lyophilized samples.

We developed a method for simultaneous quantification of the urinary 3-O-methylated catecholamine metabolites 3-methoxytyramine, normetanephrine and metanephrine by stable isotope-dilution ammonia chemical ionization mass fragmentography. Prepurification of lyophilized samples was done by simultaneous deconjugation and pentafluoropropionylation, followed by extraction and rederivatization. Compared with our previously described method, based on acid hydrolysis, alkaline extraction, derivatization and electron-impact mass fragmentography, the present method was found to be less laborious, more sensitive and presumably more accurate. New urinary excretion values were established for apparently healthy adults. The present prepurification method may prove applicable for profiling of a variety of naturally occurring mono-, di- and polyamines in biological samples.

Adult↗

The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.

BACKGROUND: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant. METHODS: We assessed a potential association between 5-HTTLPR and MDD, using the largest reported sample to date (466 patients, 836 control subjects). Individuals were all of German descent. Patients were systematically recruited from consecutive inpatient admissions. Control subjects were drawn from random lists of the local Census Bureau and screened for psychiatric disorders. RESULTS: The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26). CONCLUSIONS: These results support an involvement of 5-HTTLPR in the etiology of MDD. They also demonstrate that the detection of small genetic effects requires very large and homogenous samples.

Adult↗

Optimized preparation of urine samples for two-dimensional electrophoresis and initial application to patient samples.

OBJECTIVE: We optimized of the preparation of urinary samples to obtain a comprehensive map of urinary proteins of healthy subjects and then compared this map with the ones obtained with patient samples to show that the pattern was specific of their kidney disease. DESIGN AND METHODS: The urinary protein excretion patterns of 49 healthy men and 4 patients with renal disease were obtained by 2D electrophoresis. Silver nitrate stained protein spots were identified by mass spectrometry. RESULTS: Reproductive 2D gels identified 5 classes of proteins systematically found in healthy subjects, irrespective of age. The proteins evidenced included serum albumin and its specific proteolytic products, Tamm-Horsfall, transferrin, zinc-alpha2-glycoprotein, alpha1-microglobulin, haptoglobin, and Ig light chains. CONCLUSIONS: This study of a large panel of healthy individual showed that 2D urinary pattern was constant over time and reveal for the first time the relative abundance of albumin fragments in healthy subjects' urine. The profiles of the 4 patients, were specific of their renal disease.

Biomarkers↗

Automated zone-electrophoretic sample treatment for the analysis of biological samples by high-performance liquid chromatography.

The automation of zone-electrophoretic sample treatment for liquid chromatography is described. The procedure is completely controlled from a liquid chromatograph. The carry-over of proteins from human serum under different experimental conditions was studied. The influence of the presence of proteins in the sample is illustrated with the anionic compound salicylic acid and the increase in selectivity for cationic compounds is demonstrated with the determination of ephedrine, norephedrine and amphetamine in urine.

Amphetamine↗

Sample cleanup and reversed-phase high-performance liquid chromatographic analysis of polar aromatic compounds in groundwater samples from a former gas plant.

A method for the analysis of the polar aromatic compounds 1H-quinolin-4-one (Q), 10H-acridin-9-one (A), 5H-phenanthridin-6-one (P) and 9H-fluoren-9-one (F) in aqueous solutions has been developed. The method comprises steps for sample preparation (solid-phase extraction, cleanup) and analytical determination by means of reversed-phase high-performance liquid chromatography (RP-HPLC). For the cleanup step the suitability of two different sorbents (alternative A: silica gel, alternative B: LiChrolut EN) was investigated. Alternative B depicted several advantages, in particular higher sorbent capacity, faster and less complicated handling, higher recovery and better reproducibility. For Q, A and P, reproducibility of all method steps is better than 13%, with recovery rates ranging from 76% to 105% (n=3). Alternative B was applied to groundwater samples from a former gas plant. The analytes A and P could be detected at concentrations in the micro/l range.

Chemical Phenomena↗

Endoscopic exploration and lymph node sampling of the axilla. Preliminary findings of a randomized pilot study comparing clinical and anatomo-pathologic results of endoscopic axillary lymph node sampling with traditional surgical treatment.

OBJECTIVE: To describe the technique of endoscopic exploration of the axilla. To compare this technique to open surgical treatment by comparing the following variables: operative time, peri-operative complications, duration of hospital stay, node's histology and morphologic aspects and esthetic results. MATERIALS: Standard instruments for traditional operative laparoscopy plus a lipo-aspirator (0.8 Bar). PATIENTS: Forty patients, 20 (group A) undergoing open surgery and 20 (group B) undergoing axilloscopy. All patients with early invasive breast cancer are eligible for conservative operative treatment. METHOD: Randomized study. The technique is described and preliminary results are presented. RESULTS: The operative time for axilloscopy is approximately double that for open surgery. A comparable number of lymph nodes is collected by axilloscopy and open surgery. The nodes collected by axilloscopy are more likely to be fractured. What is the clinical consequence? Two loco-regional relapses are observed in the endoscopic group. DISCUSSION: Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling. Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure. CONCLUSION: Operative time is increased for axilloscopy compared with open surgery. The techniques yield comparable anatomo-pathologic results. It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach.

Adult↗

A multi-sample liquid scintillation counting system for weak beta-emitting samples with single phototube detectors

The relative merits of low-level liquid scintillation counters with one and two phototubes, respectively, are discussed and an analysis of their background components is presented. A simple and compact system with manual sample changing is described. It counts four samples simultaneously, and it is based on the single-phototube arrangement where conical vials sit on the top of 28 mm diameter phototubes. A PC computer collects and processes the pulses from a specially designed electronic unit. The system is operated in a small underground counting room, a closet in the wall of a road tunnel under a fjord. Its performance is described.

Journal Article↗