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Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively.

Background In vitro diagnostic bilirubin reagents based on oxidation with bilirubin oxidase or vanadic acid for total and direct-reacting bilirubin are widely used in Japan; however, their reactivity to unconjugated and conjugated bilirubin and delta bilirubin has not been completely disclosed by manufacturers. We used artificially prepared bilirubin materials to investigate the reactivity with four in vitro diagnostic bilirubin reagents. Methods Porcine unconjugated bilirubin solution, chemically synthesized ditaurobilirubin solution, and chemically synthesized delta bilirubin solution were used as surrogates of naturally occurring unconjugated bilirubin, conjugated bilirubin, and delta bilirubin, respectively. The total bilirubin and direct-reacting bilirubin concentrations were measured by three bilirubin oxidase methods and one vanadic acid method, and the observed concentrations were compared with those obtained by the diazo-based reference measurement procedure. Results The unconjugated bilirubin and delta bilirubin concentrations were similar when any of the four in vitro diagnostic bilirubin reagents were used during total bilirubin measurement. This was consistent with reference measurement procedure and exhibited a converged inter-method variation. Compared with reference measurement procedure, significantly low ditaurobilirubin concentrations were observed by the in vitro diagnostic bilirubin reagents despite the converged inter-method variation. In delta bilirubin measurement, some reagents reacted doubtfully with unconjugated bilirubin, while showed lower ditaurobilirubin concentrations than its corresponding total bilirubin concentration. Reactivity with delta bilirubin was different for each method including reference measurement procedure. Some reagents were developed to react less with delta bilirubin and others to strongly react with delta bilirubin. Conclusions We revealed the reactivity of IVD-TB and IVD-DB reagents to artificially prepared bilirubin materials, and their consistency with reference measurement procedure. The delta bilirubin data results vary depending on the reagents used.

We experienced two cases of Hb Andrew-Minneapolis with high or low-normal HbA1c levels depending on the measurement method. Case 1 was a 25-year-old male, and case 2 was a 32-year-old pregnant woman. Both cases showed normal glucose tolerance levels and glycated albumin within the reference range. In both cases, the high-performance liquid chromatography (HPLC) method (standard mode) showed high HbA1c levels of 6.8% and 6.5%, respectively, while the HbA1c levels measured by immunoassay were low normal at 4.6% in both cases. Globin gene analysis detected heterozygous β-chain mutations (β144Lys → Asn) in both cases, which resulted in the diagnosis of Hb Andrew-Minneapolis. In case 1, a high-resolution HPLC chromatogram showed multiple abnormal peaks; two unknown peaks in addition to variant hemoglobin (HbX0) and glycation products of variant hemoglobin (HbX1c) were observed after in vitro glycation reaction. Although the details of unknown peaks were not identified, those might be modified hemoglobin associated with variant hemoglobin. The presence of unknown peaks could cause high HbA1c levels measured by HPLC (standard mode). Furthermore, the HbA1c level measured by immunoassay was increased to 4.9% within the reference range after adjustment for modified hemoglobin in case 1. Consequently, the high HbA1c levels measured by HPLC (standard mode) and the low-normal HbA1c level measured by immunoassay might be due to modified hemoglobin associated with variant hemoglobin.

Variant hemoglobin is often detected during the diagnosis and treatment of diabetes mellitus. We here describe a case of α2-chain variant hemoglobin (Hb Chad) that was identified as a result of differences in HbA1cs values determined by different assays. HbA1c measured by immunoassay was thus falsely high, whereas that measured by high-performance liquid chromatography (HPLC) was slightly low. Sequencing analysis revealed a heterozygous GAG (glutamic acid) → AAG (lysine) mutation at amino acid position 23 of the α2-globin gene. This residue is located at the surface of the α-chain in the crystal structure of hemoglobin. The high HbA1c value determined by immunoassay might have been the result of increased antigenicity of the variant hemoglobin, whereas the low value measured by HPLC reflected differential fractionation of the variant relative to the wild-type protein. Hb Chad has been reported in only three cases to date, and HbA1c was measured for the first time. This is the first case where falsely high HbA1c measured by immunoassay due to increased antigenicity in α-chain variant hemoglobin. This case highlights the importance of comparison with other parameters related to plasma glucose such as glycated albumin if an HbA1c abnormality is suspected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00529-y.

HbA1c is widely used as a therapeutic target marker and as a diagnostic marker for diabetes mellitus. This has led to an increasing frequency of HbA1c measurements in current health checkups throughout Japan. In the present study, we compared the HbA1c levels measured by an enzymatic assay (EA-HbA1c) off-site during health checkups with the HbA1c levels measured by on-site ion-exchange high-performance liquid chromatography (HPLC; HPLC-HbA1c) in a hospital. A total of 96 individuals (53 males and 43 females; age, 68.9 ± 8.4 years old; 70 diabetic and 26 non-diabetic individuals) whose HbA1c levels were measured by both the methods listed above were included in the study. Since no HPLC-HbA1c levels were measured on the day of the health checkup, HPLC-HbA1c levels were estimated using HPLC-HbA1c levels measured before and after the health checkup. A significant correlation of HbA1c levels was observed between the two groups (R = 0.973; p

Porcine unconjugated bilirubin solution, chemically synthesized ditaurobilirubin solution, and chemically synthesized delta bilirubin solution were used as surrogates of naturally occurring unconjugated bilirubin, conjugated bilirubin, and delta bilirubin, respectively. The total bilirubin and direct-reacting bilirubin concentrations were measured by three bilirubin oxidase methods and one vanadic acid method, and the observed concentrations were compared with those obtained by the diazo-based reference measurement procedure.The unconjugated bilirubin and delta bilirubin concentrations were similar when any of the fourWe revealed the reactivity of IVD-TB and IVD-DB reagents to artificially prepared bilirubin materials, and their consistency with reference measurement procedure. The delta bilirubin data results vary depending on the reagents used.

Background: While good glycemic control during hospitalization has been reported to have better outcomes and reduced complications, achieving this is difficult in hospitals where diabetes specialists are not present or understaffed. Diabetes ward round by an independent and specialized team (DMWR) is one of the solutions for regular monitoring of glycemic control in inpatients, few studies existed to assess its effectiveness. Material and Methods: A team composed of two diabetes specialists, one specialized nurse, one dietician, one pharmacist, and one assistant conducted DMWR from May 2017. Hospital inpatients who were at risk of poorly controlled glycemia were given adequate advice to prevent hyperglycemia and hypoglycemia. A total of 384,422 capillary blood glucose measurements were taken from all hospitalized patients from April 2015 to March 2019 and the changes in frequency of hyperglycemic and hypoglycemic episodes were analyzed. Infection control was evaluated by episodes of blood cultures. The mortality rate at discharge and within 90 days of discharge were also calculated. Results: The odds ratio (OR) for the frequency of pre-prandial hyperglycemia before and after DMWR was 0.430 (95% confidence interval (CI): 0.407, 0.454). The OR for that of severe hypoglycemia was 0.371 (95% CI: 0.265, 0.520). The number of blood cultures was significantly reduced by 26% after DMWR. The mortality rate within 90 days of discharge was also significantly decreased in patients aged less than 65 (OR 0.363, 95%CI: 0.216, 0.609) and from 65 to 79 (OR 0.689, 95%CI: 0.541, 0.856), respectively. Conclusion: DMWR resulted in improved glycemic control and reduced staff burden for managing severe hypoglycemia and preventable infection events. Moreover, the mortality rate of patients less than 80 years of age was also reduced over the same period, suggesting that stabilizing blood sugar was beneficial for lowering mortality rate in the younger patient population. Disclosure S. Chou: None. M. Haraguchi: None. M. Imai: None. M. Ishibashi: None. M. Masano: None. Y. Iwata: None. Y. Oda: None. T. Motogami: None. S. Nakamura: None.

Background It is known that an immunoglobulin abnormality affects various clinical laboratory measurements and leads to abnormal values. We experienced a case of monoclonal gammopathy of undetermined significance (MGUS) showing a falsely low plasma glycated albumin (GA) level. Case report The patient was a 75-y-old male who visited our hospital for thrombocytosis identified during a medical checkup. Based on further examinations, he was diagnosed with MGUS (IgM-κ type). Laboratory examinations revealed that the plasma GA level was significantly low at −1.3% but the serum GA level was reasonable at 15.5%. We investigated the cause of the falsely low plasma GA level. Results The patient's plasma became turbid after mixing with the first reagent for GA measurement. The plasma GA level was increased by dilution of the plasma. The plasma GA level was falsely decreased only at the time of measurement on a sample collected using a blood-collecting tube with heparin sodium. The GA level was decreased by adding heparin sodium to the patient's serum, whereas the GA level was increased by neutralization of the patient's plasma with protamine sulfate. The GA level was increased after adding polyethylene glycol to the patient's plasma. Serum GA levels in healthy controls were decreased by adding purified M protein from the patient's serum. Conclusions We report a patient with MGUS whose plasma GA concentration was falsely decreased by M protein when blood was drawn in a heparin sodium-containing tube.

HbA1c is a widely utilized biomarker for the management of diabetes mellitus. The presence of variant hemoglobins might interfere with HbA1c measurement using different methods. We herein describe Hb Agenogi (β90Glu → Lys) with type 2 diabetes mellitus whose HbA1c measured by immunoassay (IA) showed falsely high levels while HbA1c measured by high-performance liquid chromatography (HPLC) in the standard mode (SM) showed falsely low levels. To clarify the cause of the falsely high-IA-HbA1c levels, HbA1c was measured by various methods. Glycated albumin was slightly higher than the reference range. HbA1c measured by HPLC in the variant mode, affinity assay and enzymatic assay showed the range (mean ± 2SD: 6.0–6.8%) in this case. However, HbA1c measured by several HPLC-SMs showed falsely low levels (4.1–4.4%). IA-HbA1c using an antibody manufactured by Fujirebio Inc. showed falsely high levels (7.3–8.2%); whereas, IA-HbA1c using an antibody manufactured by Roche Ltd. showed the expected range (6.2–6.5%). In the case of Hb Agenogi, IA-HbA1c using an antibody manufactured by Fujirebio yielded falsely high levels. The mutation at codon 90 of the β-globin chain might enhance antigenicity of the N-terminal peptide region and, therefore, lead to falsely high-HbA1c levels in IA-HbA1c.

Although HbA1c measurement by enzymatic assay (EA-HbA1c) is widely used in health-screening settings in Japan, recent studies have suggested lower EA-HbA1c levels as compared with HbA1c levels measured by high-performance liquid chromatography (HPLC-HbA1c). Hypothesizing that falsely low levels of EA-HbA1c are attributable to hemolysis caused by sample transport and/or storage, we measured EA-HbA1c in blood cells and whole blood after sample transport and compared them with HPLC-HbA1c levels. Blood samples were collected from ten non-diabetic individuals into sodium fluoride-containing blood collection tubes and immediately measured for EA-HbA1c in blood cells. After transport, the blood samples were again subjected to measurement of EA-HbA1c levels in blood cells and whole blood the following day. These EA-HbA1c levels were compared with HPLC-HbA1c levels. EA-HbA1c levels in blood cells measured immediately after sample collection did not significantly differ from HPLC-HbA1c levels. Transported blood samples showed hemolysis and significantly lower EA-HbA1c levels in blood cells, as compared with HPLC-HbA1c levels, whereas no significant difference was observed between EA-HbA1c levels in whole blood and HPLC-HbA1c levels. Transported blood samples showed hemolysis and falsely low EA-HbA1c levels in blood cells. Hemolysis caused by sample transport and/or storage might be responsible for the falsely low EA-HbA1c levels. This should be kept in mind, because falsely low HbA1c levels may lead to a false-negative diagnosis of diabetes.

Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initial setting, most of the laboratories answered to play a leading role in preparing the necessary matters to implementation of panic values and revise them corresponding to physician's request on each occasion. In almost all laboratories, they did not verify whether the notification procedure does work to exert appropriate clinical action. The numbers of critical values answered by the 18 laboratories distributed widely in the test items (8-39) and their critical limits (10-68). As to the critical limits, the lower limits of serum K and blood glucose converged among the laboratories, however, the limits of other test items diverged. The results of the present survey regarding to critical values, although being in small scale, may submit the im- portant issue to be solved in near future. [Short Communication].

The promotion of self-medication was announced in the "strategy for the reconstruction of Japan", which was approved in June 2013 by the cabinet, with the concepts of "extending healthy life expectancy" and estab- lishing "pharmacy-based laboratory testing services". In April 2014, the "guideline for pharmacy-based laboratory testing" was published, and approximately 1,000 pharmacies were registered as service providers as of the end of May 2015. Issues of providing pharmacy-based laboratory testing services were as follows: 1) appropriate techniques for fingertip blood sampling, 2) quality control including the maintenance and management of devices and reagents, 3) infection prevention, and 4) provision of information on examination results and factors affecting the examination to examinees. The improvement of health screening rates remains to be resolved in order to achieve "extension of healthy life expectancy" and reduce medical costs. The involvement of clinical testing specialists is essen- tial to resolve the above issues for the appropriate management of pharmacy-based laboratory testing ser- vices. [Review].

ObjectivesThree multicentre studies of reference intervals were conducted recently in Japan. The Committee on Common Reference Intervals of the Japan Society of Clinical Chemistry sought to establish common reference intervals for 40 laboratory tests which were measured in common in the three studies and regarded as well harmonized in Japan.MethodsThe study protocols were comparable with recruitment mostly from hospital workers with body mass index ≤28 and no medications. Age and sex distributions were made equal to obtain a final data size of 6345 individuals. Between-subgroup differences were expressed as the SD ratio (between-subgroup SD divided by SD representing the reference interval). Between-study differences were all within acceptable levels, and thus the three datasets were merged.ResultsBy adopting SD ratio ≥0.50 as a guide, sex-specific reference intervals were necessary for 12 assays. Age-specific reference intervals for females partitioned at age 45 were required for five analytes. The reference intervals derived by the parametric method resulted in appreciable narrowing of the ranges by applying the latent abnormal values exclusion method in 10 items which were closely associated with prevalent disorders among healthy individuals. Sex- and age-related profiles of reference values, derived from individuals with no abnormal results in major tests, showed peculiar patterns specific to each analyte.ConclusionCommon reference intervals for nationwide use were developed for 40 major tests, based on three multicentre studies by advanced statistical methods. Sex- and age-related profiles of reference values are of great relevance not only for interpreting test results, but for applying clinical decision limits specified in various clinical guidelines.

Background Glycated albumin is an intermediate glycaemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing glycated albumin measurements. Methods The isotope dilution liquid chromatography/tandem mass spectrometry method was developed as a reference measurement procedure for glycated albumin. The stable isotopes of lysine and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by liquid chromatography/tandem mass spectrometry, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of glycated albumin were prepared from pooled patient blood samples. Results The isotope dilution–tandem mass spectrometry calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The inter-assay and intra-assay coefficient of variation values of glycated albumin measurement were 1.2 and 1.4%, respectively. The glycated albumin values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of glycated albumin values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples. Conclusion The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the isotope dilution liquid chromatography/tandem mass spectrometry method as a reference measurement procedure, and JCCRM611 as a certified reference material for glycated albumin measurement. In addition, we recommend the traceability system for glycated albumin measurement.

Background The aim of the present study was to evaluate standard reference material (SRM) 1955 commutability as a reference material for serum folate using automated methods. We also designed so as to reduce the intermethod variability present in different automated methods. Methods Using a microbiological assay related to the ‘information value’ of SRM 1955 as a comparison method, we investigated the possibility of standardization for the assay values of serum folate as measured by the automated methods (Access, Centaur and Elecsys). In the assay of 50 patient sera by these automated methods, we corrected observed values by the SRM 1955 and compared with comparison values. Results The observed values of SRM 1955 Levels I, II and III were within or outside (but near) a 95% prediction interval obtained from patient sera by the automated methods. The normalized residuals obtained from SRM 1955 were within ±3.0 (in SD units), which enabled us to conclude that the SRM 1955 had a physicochemical characterization similar to native serum. Twelve patients were assessed as hypofolataemia (Conclusions The use of SRM 1955 would help to reduce the intermethod variability present in different automated methods for serum folate measurement.

The cost, speed, and quality are the three important factors recently indicated by the Ministry of Health, Labour and Welfare (MHLW) for the purpose of accelerating clinical studies. Based on this background, the importance of laboratory tests is increasing, especially in the evaluation of clinical study participants' entry and safety, and drug efficacy. To assure the quality of laboratory tests, providing high-quality laboratory tests is mandatory. For providing adequate quality assurance in laboratory tests, quality control in the three fields of pre-analytical, analytical, and post-analytical processes is extremely important. There are, however, no detailed written requirements concerning specimen collection, handling, preparation, storage, and shipping. Most laboratory tests for clinical studies are performed onsite in a local laboratory; however, a part of laboratory tests is done in offsite central laboratories after specimen shipping. As factors affecting laboratory tests, individual and inter-individual variations are well-known. Besides these factors, standardizing the factors of specimen collection, handling, preparation, storage, and shipping, may improve and maintain the high quality of clinical studies in general. Furthermore, the analytical method, units, and reference interval are also important factors. It is concluded that, to overcome the problems derived from pre-analytical processes, it is necessary to standardize specimen handling in a broad sense.

Currently, the NGSP value for HbA1c is widely used as the global standard. In Japan, the JDS value was replaced with the NGSP value in clinical practice on April 1, 2012. From April 2013, the NGSP value will also be used in health examinations. In April 2014, the HbA1c value will be consolidated into the NGSP value. Since the JDS did not finalize the timeline for the replacement until the last moment, clinical laboratories and manufacturers were left behind with little time for preparation; however, introduction of the NGSP value caused little confusion in clinical practice. It is speculated that the reason for the lack of confusion was either because dissemination of the NGSP replacement among clinicians, patients, and co-medicals was effective, or JDS and NGSP values were listed side by side in current clinical practice. Real confusion might occur when consolidation of the NGSP value becomes effective in April 2014. The final goal of international standardization of the HbAlc value will be achieved by enabling the measurement of HbA1c, which will be traced back to SI units in the future.

Chronic inflammation is involved in the pathogenesis of cardiovascular diseases (CVD). Several prospective studies have indicated that an elevated high sensitive C-reactive protein (hs-CRP) level is a risk factor for CVD. These results were also confirmed by prospective studies in Japan both for primary and secondary prevention. A randomized control study using statins also revealed that lower levels of both LDL cholesterol and hs-CRP were independently related to the incidence of CVD. Recent meta-analysis revealed that hs-CRP was a risk factor not only for CVD but for other diseases including cancers. It revealed that the absolute value of hs-CRP varied among the study populations. The mechanism of how hs-CRP is associated with the pathogenesis of CVD is not fully understood. Generally, inflammation in the vascular wall and the release of inflammatory cytokines from macrophages was considered to the main mechanism, but infection with such as chlamydia or Helicobacter pylori, and periodontal disease have been postulated as the causes of systemic inflammation. Recently, visceral fat accumulation and its cross-interaction with inflammatory cells have been proposed as the cause of systemic inflammation as "innate inflammation". Our original cross sectional studies also showed the correlations of hs-CRP with BMI and triglyceride. Although there is no specific therapy for the reduction of hs-CRP, we have to consider hs-CRP as a risk factor for CVD which complements other classical risk factors.

The purpose of this study was to contribute to the quality management in the fields of clinical studies and clinical trials. To accomplish this purpose we tried to make guidelines for nationwide standardization of clinical tests. This study was performed by multidisciplinary personnel such as medical doctors, medical technologist, CRC, and representatives of pharmaceutical companies and/or clinical laboratory testing companies. The study was also focused on two fields of clinical tests such as pre-analytical and post-analytical phase. Each member shared various incidents and tried to make solutions. In post-analytical area in particular, further discussion concerning CDISC and SS-MIX was done. Based on these efforts, a tentative guideline was made.

Objectives To determine the usefulness of alpha 1 -antichymotrypsin-prostate-specific antigen (PSA) complex (PSA-ACT)-based parameters in predicting bone metastasis in patients with prostate cancer. Methods PSA-ACT, total PSA, free PSA, their volume-adjusted values, and alkaline phosphatase were evaluated in 220 consecutive patients with newly diagnosed prostate cancer. Results Bone metastases were detected by bone scan in 27 (12.3%) of the 220 patients. The serum levels of PSA-ACT, total PSA, free PSA, PSA density, PSA adjusted for transition zone volume, PSA-ACT density, PSA-ACT adjusted for transition zone volume, alkaline phosphatase, PSA-ACT/PSA ratio, and Gleason score in patients with bone metastases were each significantly greater than in those without bone metastases. On receiver operating characteristic analyses, PSA-ACT had the greatest area under the curve (0.88), but the receiver operating characteristic curve demonstrated that the sensitivity and specificity of PSA-ACT were marginally better than those of total PSA at only a few selected cutoff points. At a sensitivity of 93% (2 patients with bone metastasis missed), unnecessary bone scans would have been avoided in 107 and 102 patients using a PSA-ACT cutoff value of 10 ng/mL and total PSA cutoff value of 11.5 ng/mL, respectively. Multivariate logistic regression analysis demonstrated that PSA-ACT and Gleason score were significant independent predictors of bone metastasis. Conclusions PSA-ACT is as useful as total PSA for identifying patients with a low probability of having bone metastasis. PSA-ACT could replace PSA for predicting negative bone scans in a clinical setting in which PSA-ACT is used for monitoring and screening patients for prostate cancer.

Objective: Cardiopulmonary bypass (CPB) affects hepatocellular integrity and occasionally results in liver dysfunction after cardiac surgery. Performing coronary artery bypass graft surgery without CPB may help to reduce the risk of this complication and better preserve perioperative liver function. This study compared perioperative hepatocellular damage in patients undergoing on-pump and off-pump bypass surgery. Design: Prospective study. Setting: University hospital. Participants: Patients scheduled for elective on-pump (n = 21) and off-pump (n = 17) coronary artery bypass surgery. Measurements and Main Results: Liver function was assessed by serum levels of alcohol dehydrogenase (AD) and α-glutathione S-transferase (α-GST), which serve as more sensitive indices of hepatocellular injury than do conventional transaminases. Arterial blood was sampled at 6 stages: after induction of anesthesia (baseline); at the end of CPB in the on-pump group or on completion of the last distal anastomosis in the off-pump group; at the end of surgery; and 6 hours, 12 hours, and 24 hours after the end of anesthesia. The off-pump patients showed significantly lower increases in serum AD and α-GST levels than did the on-pump group. AD and α-GST values increased in the on-pump patients after the initiation of CPB and peaked at the end of surgery, with a return to baseline at 12 hours and 24 hours after the end of anesthesia. No clinically relevant liver dysfunction was observed in either group. Conclusions: CPB induced transient subclinical hepatocellular damage, whereas off-pump revascularization attenuated this damage.

The standardization of the total PSA assay was considered internationally after 1992, when the first Stanford Conference was organized by Prof. Dr. T. Stamey (Stanford University). In Japan, an analytical survey was carried out three times in the past six years by the committee of PSA standardization. The discrepancy in PSA values among each assay system was determined and the cause of discrepancy was studied. As a result, the principal cause of each discrepancy between kits was revealed, and 34% of all kits in the 1997 survey, 73% in the 2000 survey and 84% in 2003 were classified as equimolar response kits. The inter-kit variability of total PSA assay value was improved drastically. The standardization of the PSA assay has made great progress based on the establishment of purification of PSA from the seminal fluid pool and the guideline of value assignment approved by the NCCLS. In Japan, the special committee of PSA standardization was formed by the JCCLA in 2002. In this committee, we are considering the establishment of a reference measurement system including serum-based reference material, which is inactivated protease inhibitor, due to the traceability of the PSA concentration from the primary reference material that was certified by the WHO for patient serum.

With the increase in clinical examination items, and with the specialization of clinical medicine, physicians' requests for consultations on laboratory medicine is getting more evident. However, at present in many hospitals laboratory staff do not always make appropriate answers to the questions from physicians in various fields because the laboratories are divided in terms of examination fields. In our hospital, we established a consultation division responding to every inquiry from clinical staff with a full-time technologist. At present the division is functioning very well, suggesting that laboratory technologists must build close relations with clinical staff and that the technologist's task is very diverse, not confined to just analyzing samples.

To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy.One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy.Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer.alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

C-Reactive protein (CRP) is a well-known indicator of inflammation. Advances in laboratory technology have enabled its quantification at lower concentrations by an automated analyzer (1)(2)(3). Because an increase in serum CRP concentration, even within the reference intervals of conventional analytic methods, has been related to increases in the risk of atherothrombotic events (4)(5)(6)(7), efforts for CRP quantification are currently directed toward healthy, elderly individuals or populations at risk of atherosclerotic diseases. When measured with a high-sensitivity analytic method, CRP may have diagnostic value in neonatal infection because newborns are unable to produce sufficient amounts of acute-phase proteins (8) and respond to infection with a smaller increase in CRP compared with that in adults (9). The utility of CRP for the diagnosis of neonatal infection has been the subject of lengthy controversy because of its unsatisfactory sensitivity for early-onset neonatal infection (10)(11)(13). The CRP concentration increases physiologically in newborns within the first few days after birth (9)(13). This increment seems to be related to the low diagnostic accuracy of CRP measurements in neonatal infection, particularly when measured shortly after birth. Similarly, other indicators of inflammation, such as procalcitonin and interleukin-6, demonstrate increases in noninfected babies within a few days after birth (14)(15)(16). In addition, very low CRP concentrations are found in the cord blood and sera of neonates in the immediate postnatal period (17). Therefore, the postnatal physiologic changes in CRP remain poorly understood. In this context, elucidation of serum CRP kinetics and an understanding of the mechanism(s) that cause its increase in the immediate postnatal period in noninfected babies would improve its diagnostic accuracy for early-onset neonatal infection. Using a high-sensitivity analytic method, we analyzed the serial changes in …

BACKGROUND Several methods for the identification of patients with prostate carcinoma have been proposed to enhance the clinical usefulness of prostate specific antigen (PSA). However, it remains unclear which method is superior in practical use. The authors attempted prospectively to identify the most powerful method with which to detect prostate carcinoma, especially among patients with intermediate PSA levels. METHODS Between October 1997 and August 1999, systematic sextant biopsies were performed on 281 patients, including 147 with PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA density of the transition zone (PSATZD) for the detection of prostate carcinoma were compared by using receiver operating characteristic (ROC) curves and logistic regression analyses. RESULTS According to ROC curve analysis, PSATZD had the greatest area under the curve in the overall patient population and in patients with intermediate PSA levels. In patients with intermediate PSA levels, at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68 of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25 patients, respectively. Stepwise logistic regression analysis showed that PSATZD and findings on digital rectal examination were significant independent predictors. CONCLUSIONS PSATZD had the most useful validity in the differentiation between prostate carcinoma and benign prostatic enlargement in the overall patient population and in patients with intermediate PSA levels. Cancer 2000;89:842–9. © 2000 American Cancer Society.

The landscape of prostate cancer has changed since the appearance of the first prostate-specific antigen (PSA) assay. PSA testing has gained rapid recognition since M. Kuriyama et al. (1) of Roswell Park first reported clinical studies using an enzyme immunoassay with anti-PSA rabbit antibody. Mikolajczyk and coworkers (2)(3) reported the presence of several free PSA isoforms and the potential application of free PSA isoforms as serum markers. Today, more than 30 types of total PSA assay reagent sets and ∼10 types of free PSA and PSA–α1-antichymotrypsin (ACT) assays, based on various principles, are available. Key elements in PSA measurement are interchangeability of assays and stability of serum samples before tests (4)(5). Efforts to standardize PSA assays were initiated in 1992 at the First Stanford Conference, organized by T. Stamey. At the Second Stanford Conference on International Standardization of Prostate-Specific Antigen (1994), Stamey et al. (6) proposed a primary calibrator consisting of 90% purified PSA-ACT and 10% free PSA (90:10) on a molar basis. Subsequently, the Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) issued a document (7) recommending a set of 3 distinct materials containing 100% free PSA, 100% PSA-ACT, and 90% PSA-ACT:10% free PSA. This document led to further activity in the harmonization of PSA assays. In 1999, Robert M. Nakamura, a member of the International Consultation Committee on Prostate Cancer, made recommendations, with his colleagues (8), on standardization and quality assessment of …