Utilization of common inflammatory markers in new, symptomatic, primary care outpatients based on their cost-effectiveness.

Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.     

Leukocyte-Endothelium Interaction in the Rat Mesenteric Microcirculation during Halothane or Sevoflurane Anesthesia

Background: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules.

Methods: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins.

Results: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29.     

Extracardiac Direct Total Cavopulmonary Connection

We report a successful extracardiac direct total cavopulmonary connection without prosthetic materials performed in a 3-year-old boy with tricuspid atresia, infundibular pulmonary stenosis, and normally positioned great arteries. The transected pulmonary trunk was bought down posterolaterally with respect to the right atrium and was anastomosed end-to-end with the inferior vena cava.     

Genomic analysis in Candida albicans]

With the recent advances in DNA sequencing technology, a succession of entire genome sequences have been published. A number of genome projects are underway in pathogenic fungi. From these, we present the history and current status of the genomic analysis of Candida albicans. The sequencing project for this organism has been undertaken at Stanford University, and is now nearing the end.     

A new quality control method based on a moving average of "latent reference values" selected from patients' daily test results

The average of normals(AON) method is a quality control(QC) method that uses measured values of patients' samples instead of QC samples. Because this method is easily affected by fluctuations in the patient population and is insensitive to short-term changes in test values, we developed an alternative method based on the moving average(MA) of latent reference values(LRVs) which are the test results of patients whose other related test results are all within reference intervals. We evaluate the new methodology(MALRV) using seven commonly measured biochemical tests. The LRV of each test were selected with reference to four other items that had the highest coincidences of abnormality. The optimum amount of data needed to compute the MA is determined as that making the coefficient of variation(CV) of the consecutive MA over a study period less than 5.0%. The MALRV is computed each time a new LRV is encountered to monitor quality status continuously. The MALRV CV was within 5.0% when sample sizes were between 20 and 110. When shift and trend simulations were performed with the patient data, the corresponding alterations were detected. MALRV is a useful measure for detecting short-term alterations in patient test results, supplementing the conventional QC chart method.     

Involvement of nitric oxide in glucose toxicity on differentiated PC12 cells: prevention of glucose toxicity by tetrahydrobiopterin,a cofactor for nitric oxide synthase

Effects of high concentrations of glucose on cell survival of differentiated PC12 cells were examined. Seven day-culture with D-glucose (9.0-27.0 mg/ml as 2-6-fold of the optimal level) induced cell death in a dose-related manner but 3-day culture with high concentrations of glucose had no effect on cell viability. L-glucose had no effect on viability of PC12 cells, suggesting that D-glucose toxicity was independent of its osmolarity effect. Seven-day culture with D-glucose (13.5 mg/ml as 3-fold of the optimal level) increased nitric oxide metabolites (NOx) in the culture medium. Glucose-induced increase in NOx was eliminated by 0.1 mM L-nitro-arginine methylester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Intracellular Ca(2+) concentration was increased by D-glucose in a dose-related manner, suggesting that D-glucose activated NOS by increasing intracellular Ca(2+) concentration in PC12 cells. Glucose-induced cell death was blunted by 0.1 mM L-NAME, showing that nitric oxide (NO) was involved in the glucose toxicity to PC12 cells. Tetrahydrobiopterin (BH(4)), a cofactor for NOS, attenuated both glucose-induced cell death and NOx production at 1 microM but not at 10 microM. The effects of BH(4) on glucose-induced cell death and NOx production were not mimicked by reducing agents such as ascorbate and cysteine. These results taken together suggest that high concentrations of glucose induced cell death via NO production and that low concentration of BH(4) had a protective effect against glucose neurotoxicity in differentiated PC12 cells.     

Analysis of the dilution deviation in CA19-9 measurement

CA19-9 widely used as a tumor marker of the pancreas and a bile duct. There are a number of reports which describes the measured value discrepancies between RIA and non-RIA kits. RIA results also have shown lack of the linearity over 70 U/ml when the samples are diluted. The pH condition at assay reaction for RIA had been suggested as the major reason, it has been denied by the results from the same pH condition at assay reaction used by COBAS CORE CA19-9 EIA II. On the other hand, the lack of RIA antibody titer is indicated for the discordant results by changing the sample volume to reagent volume ratio in the reaction. Our further investigation also indicates that the specific Lewis blood type, i.e. Le (a-b+), shows the linearity issues by RIA. The discrepancies are not caused by the reaction pH, but the amount of the antibody used in the RIA kit is closely associated. Considering the CA19-9 antibody nature used in RIA kit, which covers broad molecular range, users need to pay more attention to setting up each laboratory's measuring range.     

Lyotropic mesophase of imogolite, 1. Effect of polydispersity on phase diagram

The acidic aqueous solution of imogolite is proposed to be an ideal lyotropic system. No temperature dependence was marked on the two phase boundary concentrations (A and B points) of imogolite solutions as predicted by the theories of Flory and Onsager. A satisfactory quantitative agreement was observed with Onsager's theory. The polydispersity of rod lengths was found to shift the A point towards lower concentrations than expected from theory.     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.