[Challenges and Outcomes of the Process for Achieving Certification].

Clinical laboratory tests have been indispensable for medical services in recent years, and such a situation is associated with the offering of accurate test results by clinical laboratory units. A large number of facilities wishing to achieve ISO 15189 Certification follow preparatory procedures with support from consulting companies. However, in our facility, a limited budget did not allow us to use such services. As a solution, we participated in the Future Lab Session in OSAKA (FLS), a support group for the achievement of ISO 15189 Certification, when it was organized. Aiming to extensively cover and fulfill its responsibility for all processes, including clinical interpretations of the results obtained through patient preparation, in order to continuously offer high-quality test results to clinicians, our clinical laboratory unit underwent examination for certification, and consequently realized the necessity of third-party evaluation. The provision of laboratory services, fully complying with these standards, contributes to medical safety, in addition to accuracy improvement. Although the certification and its maintenance are costly, it is sufficiently cost-effective to achieve it, when focusing on improved efficiency and the enhanced quality and safety of medical services after work standardization.

[A 28-Week-Pregnant Woman at Twenty Years of Age, Who Had Been Hospitalized with Jaundice].

The Reversed Clinicopathological Conference (R-CPC) is a useful tool to analyze a patient's condition us- ing only laboratory data. An R-CPC was held at the 59th Regional Congress. One case presenter, two dis- cussers, and one commenter participated in this R-CPC. We report a 28-week-pregnant woman at twenty years of age, who had been hospitalized with jaundice. In laboratory data, AST, ALT, and bilirubin were ele- vated and the prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. Although the liver failure was improved after she delivered a baby by Caesarean section, postoperative intra- peritoneal bleeding persisted. The diagnosis based on liver biopsy was autoimmune hepatitis. Although the bleeding was stopped on the seventh postoperative day, the prolongation of PT and APTT remained. LA was positive in the diluted Russell's viper venom time. Anti-cardiolipin and anti-beta-2-glycoprotein anti- bodies were also positive. The prothrombin activity was reduced. A high titer of phosphatidylserine- dependent anti-prothrombin antibody (aPS/PT), which causes bleeding, was observed. Based on these data, she was diagnosed with lupus anticoagulant-hypothrombinemia syndrome (LAHS). The 2 discussers care- fully analyzed the laboratory data and the commenter gave appropriate opinions. [Review].

[Hemolytic Anemia with Excessively Elevated Lactic Dehydrogenase Levels].

It has become easier to acquire patients' clinical information from clinical laboratories using the electronic medical record system. However, it is possible that clinical laboratories do not consider abnormal laboratory data when elucidating the pathological mechanism of diseases in patients when their clinical information is obtained from the electronic medical records. In this reversed clinicopathological conference, we analyzed the laboratory data of a patient with elevated lactate dehydrogenase (LD) levels and anemia. Although the presence of hemolysis was clear from the elevated LD levels, anemia, and decreased haptoglobin levels, the ,excessive increase in the LD level suggested a particular mechanism of hemolysis. Drug intake was sus- pected on the basis of a prolonged prothrombin time with a normal activated partial thromboplastin time. At the conference, these findings led to in-depth discussions. We elucidated the pathological mechanism in this patient based only on the laboratory data, with intentionally restricted clinical information, and again recog- nized the importance of analyzing laboratory data thoroughly. Training modules for medical technologists and doctors in clinical laboratories that provide information regarding elucidating pathological mechanisms using laboratory data may prove useful for improving the nature of comments in laboratory data reports. In addition, clinicians should also receive training to elucidate the pathological mechanism of a disease on the basis of only laboratory data, as well as training for diagnosing patients on the basis of clinical information and physical examination findings. [Review].

[A Case of Lupus Anticoagulant-Hypoprothrombinemia Syndrome with Phosphatidylserine-Dependent Anti-Prothrombin Antibody].

Lupus anticoagulant-hypothrombinemia syndrome (LAHS) is a rare disease involving hemorrhagic diathe- sis due to hypothrombinemia with lupus anticoagulant. We report a 28-week-pregnant woman at twenty years of age, who had been hospitalized with jaundice. In laboratory data, AST, ALT, and bilirubin were elevated and the prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. Although the liver failure was improved after she delivered a baby by Caesarean section, postoperative intraperitoneal bleeding persisted. The diagnosis by liver biopsy was autoimmune hepatitis. Although the bleeding was stopped on the seventh postoperative day, the prolongation of PT and APTT remained. LA was positive in the diluted Russell's viper venom time. Anti-cardiolipin and anti-beta-2-glycoprotein anti- bodies were also positive. The prothrombin activity was reduced. A high titer of phosphatidylserine- dependent antiprothrombin antibody (aPS/PT), which causes bleeding, was observed. Based on these data, she was diagnosed with LAHS. The liver dysfunction and prolongation of PT and APTT were normalized following the administration of corticosteroids. In this case, aPS/PT may have contributed to the pathological physiology of LAHS. [Case Report].

Validation of two automatic devices: Omron HEM-7252G-HP and Omron HEM-7251G for self-measurement of blood pressure according to the European Society of Hypertension International Protocol revision 2010.

OBJECTIVE: The aim of this study was to validate the performance of Omron HEM-7252G-HP and Omron HEM-7251G for monitoring upper arm blood pressure (BP) in accordance with the European Society of Hypertension International Protocol revision 2010 (ESH-IP revision 2010). METHODS: Three trained medical doctors validated the performance of these devices by comparing data obtained from these devices with those obtained using a standard mercury sphygmomanometer. We included 33 participants (19 men and 14 women for the experiment using HEM-7252G-HP; 16 men and 17 women for the experiment using HEM-7251G). The mean age of the participants was 50±12 and 53±10 years in the respective studies. RESULTS: The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 76, 92, and 97% for systolic BP (SBP) and 83, 97, and 99% for diastolic BP (DBP), respectively, in the Omron HEM-7252G-HP and 77, 92, and 99% for SBP and 85, 94, and 98% for DBP, respectively, in the Omron HEM-7251G in the part 1 analysis; both SBP and DBP passed the part 1 and part 2 criteria.The mean differences between the device and mercury readings for SBP and DBP were as follows: HEM-7252G-HP, -1.5±5.1 and -1.2±3.9 mmHg, respectively; HEM-7351G, -0.6±4.7 and -0.2±4.4 mmHg, respectively. CONCLUSION: The Omron HEM-7252G-HP and HEM-7251G passed all the requirements of the ESH-IP 2010 revision.

Validation of two automatic devices for the self-measurement of blood pressure according to the ANSI/AAMI/ISO81060-2:2009 guidelines: the Omron BP765 (HEM-7311-ZSA) and the Omron BP760N (HEM-7320-Z).

BACKGROUND: Allowing patients to measure their blood pressure (BP) at home will be the standard for evaluating the disease state as the process of clinical diagnosis, and it is recognized as having great clinical utility. To measure BP as accurately as possible, innovative techniques have been incorporated into home BP measurement devices. OBJECTIVE: The present study aimed to evaluate the performance of the Omron BP765 (HEM-7311-ZSA) and the Omron BP760N (HEM-7320-Z), which are equipped with functions to detect irregular pulses and arm movement that lead to inaccurate BP readings. METHODS: A team of three trained medical doctors validated the performance of these devices by comparing the data alternatively obtained from both devices with those from a standard mercury sphygmomanometer. RESULTS: The magnitude of the difference in BP readings between the tested device and the standard mercury sphygmomanometer in the Omron BP765 and BP760N was within the range of ±3 mmHg (mean) allowed by the American National Standards Institute, Inc/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2009 guidelines. CONCLUSION: The Omron BP765 and BP760N were found useful for the self-measurement of BP at home, and their performance fulfilled the requirement of the ANSI/AAMI/ISO 81060-2:2009 guidelines.

Validation of three automatic devices for the self-measurement of blood pressure according to the European Society of Hypertension International Protocol revision 2010: the Omron HEM-7130, HEM-7320F, and HEM-7500F.

OBJECTIVE: The aim of the present study was to validate the Omron HEM-7130, HEM-7320F, and HEM-7500F for monitoring upper arm blood pressure (BP) according to the European Society of Hypertension International Protocol revision 2010 (ESH-IP revision 2010). METHODS: Three trained medical doctors validated the performance of these devices by comparing the data obtained from the devices with those of a standard mercury sphygmomanometer. We included 33 participants (20 men and 13 women for the HEM-7130 experiment; 18 men and 15 women for the HEM-7320F experiment; and 21 men and 12 women for the HEM-7500F experiment). The mean age of the participants was 49±15, 50±11, and 50±11 years in the respective studies. RESULTS: The mean differences between the device and the mercury readings for systolic and diastolic BP were as follows: HEM-7130, -1.8±5.3 and -0.1±4.0 mmHg, respectively; HEM-7320F, -0.9±4.7 and -1.9±4.4 mmHg, respectively; and HEM-7500F, -1.0±4.6 and -1.1±4.0 mmHg, respectively. These findings indicated that the device was reading lower than the mercury. However, the number of absolute differences between the devices and observers fulfilled the requirement of the ESH-IP revision 2010. CONCLUSION: The Omron HEM-7130, HEM-7320F, and HEM-7500F passed all the requirements of the ESH-IP 2010 revision. Therefore, we recommend these devices for the home measurement of BP in adults.

[A Case of Heparin-Induced Thrombocytopenia with Discrepancy in the Results of Anti-Platelet Factor 4/Heparin Antibodies between Latex-Particle-Enhanced Immunoturbidimetric Assay and Enzyme Immunoassay].

A female patient in her seventies with diabetes mellitus, hyper-lipidemia and mitral regurgitation was admitted because of the acute heart failure. She was treated with diuretics and vasodilators, however these were not effective. Therefore the CHDF using heparin was required for the patients. After the introduction of CHDF, the platelet count subsequently decreased to less than 7.0 x 10(4)/µl. After stopping CHDF, the platelet count recovered. In the second CHDF treatment, the platelet count decreased again. HIT was suspected because of both the usage of heparin and five points of 4T's score in the patient. Heparin was discontinued immediately and then her platelet count improved. The HIT antibody by latex-particle-enhanced immunoturbidimetric assay was performed simultaneously, however it was not detected. After re-using heparin by heparin lock, platelet count had been decreasing. Furthermore the thrombus was observed in the infusion tube. We considered that a clinical course did not accord with the result of HIT antibody. We measured HIT antibody by another method, an enzyme immunoassay (EIA), and the positive antibody was observed. We encountered a rare case with discrepancy in the results of HIT antibody between two methods. When HIT is suspected by the results from the clinical course and 4T's score, even though the negative HIT antibody, heparin should be discontinued and the different assay for HIT antibody such as an EIA in this case should be performed.

[The basic research on the high-sensitive troponin I assay, and the application to evaluation of chronic heart failure].

The mortality among patients with heart diseases increases steadily in an aging society like Japan. Among those, the patients with chronic heart failure (CHF) are thought to be increasing rapidly although the official report is missing. It is well-known that BNP or NT-proBNP is useful for a clinical diagnosis of CHF, but a role of the cardiac troponin (cTn) attracts attention as a novel biomarker of their prognosis. However, because the level of cTn in patients with CHF is far lower than that in cases of acute coronary syndrome (ACS), development of the high-sensitive method with precision is desired. In the present study, a new sensitive assay system with an analyzer, ARCHITECT STAT (cTnI hs-ARCH) was basically studied and found more sensitive than other conventional 2 sensitive methods. The performance of cTnI hs-ARCH was evaluated in patients with CHF by comparing it to findings with other 2 methods. When CHF patients are allocated into categories of NYHA classification according to their subjective symptoms, cTnI hs-ARCH was superior to other methods in discriminating subgroups. In addition, multivariable analysis disclosed that cTnI hs-ARCH is influenced by the level of renal function at the minimum among the 3 methods. Therefore, cTnI hs-ARCH may be a useful method for evaluation of prognosis in patients with CHF who often have impaired renal function.

Validation of Omron RS8, RS6, and RS3 home blood pressure monitoring devices, in accordance with the European Society of Hypertension International Protocol revision 2010.

BACKGROUND: Allowing patients to measure their blood pressure at home is recognized as being of clinical value. However, it is not known how often these measurements are taken correctly. Blood pressure monitors for home use fall into two types based on the position of the cuff, ie, at the upper arm or the wrist. The latter is particularly convenient, as measurements can be taken fully clothed. This study aimed to evaluate the performance of the wrist-type blood pressure monitors Omron RS8 (HEM-6310F-E), Omron RS6 (HEM-6221-E), and Omron RS3 (HEM-6130-E). METHODS: A team of three trained doctors validated the performance of these devices by comparing the measurements obtained from these devices with those taken using a standard mercury sphygmomanometer. All the devices met the validation requirements of the European Society of Hypertension International Protocol revision 2010. RESULTS: The difference in blood pressure readings between the tested device and the standard mercury sphygmomanometer was within 3 mmHg, which is acceptable according to the European Society of Hypertension guidelines. CONCLUSION: All the home devices tested were found to be suitable for measuring blood pressure at home because their performance fulfilled the requirement of the guidelines.

[Performance and clinical utility of a high-sensitivity troponin T assay].

In the present study, we evaluated the performance and clinical utility of a high-sensitivity troponin T (hs-cTnT) assay. The within- and between-assay variations (coefficients of variation: CV) in the low and high concentrations of troponin T in serum samples were 0.84% to 3.34%, respectively. Analysis of interferents showed that only hemoglobin negatively influenced the assay results. Blank assay was < 0.001 ng/mL, and a limit of quantification (10% CV) was found at 0.005 ng/mL. The correlation coefficient (r) between hs-cTnT and the conventional assay was 0.997 (p < 0.000). The high-sensitivity assay system could detect cTnT in 88% of samples in which the conventional assay could not detect any immunoreactivity. The 99th percentile in healthy subjects, determined using 559 samples from medical checkups, was 0.011 ng/mL. There was a gender difference (hs-cTnT levels were higher in men than in women), and hs-cTnT levels increased with age. Because hs-cTnT level exceeded 0.011 ng/mL approximately 2 hours after the onset of chest pain in patients with acute myocardial infarction, hs-cTnT can serve as a biomarker for early detection of myocardial infarction. There was a positive correlation (r = 0.491, p < 0.001) between hs-cTnT and NT-proBNP, and hs-cTnT levels increased with the progression of the disease state, as assessed using New York Heart Association (NYHA) classification. These findings indicate that the hs-cTnT assay is sensitive enough to diagnose early-stage acute myocardial infarction and congestive heart failure.

Ca2+ entry mode of Na+/Ca2+ exchanger as a new therapeutic target for heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of heart failure with preserved ejection fraction (HFPEF). Plasma level of digitalis-like factors (DLFs) is increased in patients with hypertension, a principal underlying cardiovascular disease of HFPEF. Digitalis-like factors inhibit ion-pumping function of Na(+)/K(+)-ATPase and activate the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger (NCX). Digitalis-like factors are known to promote collagen production in fibroblasts. The aim of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in the prevention of LV fibrosis and in the development of HFPEF. METHODS AND RESULTS: (i) Dahl salt-sensitive rats fed 8% NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24 h urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (ii) Continuous administration of ouabain for 14 weeks developed LV fibrosis without affecting blood pressure in Sprague-Dawley rats. (iii) Ouabain elevated intracellular Ca(2+) concentration through the entry of extracellular Ca(2+), increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced (3)H-proline incorporation in cardiac fibroblast; and SEA0400, the inhibitor of the NCX entry mode, suppressed these effects. (iv) In the HFPEF model, administration of SEA0400 at subdepressor dose improved the survival rate in association with the attenuation of LV fibrosis and stiffening. CONCLUSION: Digitalis-like factors and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin-angiotensin-aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na(+)-ENaC-RAAS-EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.

An ouabain-like factor is secreted from immortalized hypothalamic cells in an aldosterone-dependent manner.

Ouabain-like factor (OLF) modulates blood pressure via sodium pump inhibition in the central nervous system and in the peripheral circulation. Ouabain-like factor (OLF) is thought to be produced in the adrenal gland and hypothalamus, and it may relate locally to the renin-angiotensin-aldosterone system. However, the evidence for the latter was obtained from in vivo experiments using animals. In the present study, we investigated ouabain production in the immortalized hypothalamic cell line N1. First, cell culture supernatant was collected from the immortalized hypothalamic cell line N1 at 0.5, 4, 8, and 24 h. A newly developed enzyme-linked immunosorbent assay (ELISA) that used anti-ouabain antibody showed that immunoreactivity in the supernatant was increased significantly at 24 vs. 0.5 h (0.01±0.004 vs. 0.16±0.033 pmol/mg protein, p<0.01). A combination of HPLC and ELISA was used to characterize N1 cell-derived OLI, showing that the highest peak of OLI had the same retention time as authentic ouabain. Thereafter, N1 cells were cultured with (1-10 µM) aldosterone, and supernatant was collected after 24 h of culture. In addition, N1 cells were cultured with 5 µM eplerenone, a mineralocorticoid receptor blocker, plus aldosterone. OLI was significantly increased in the supernatant of the cells cultured with 10 µM aldosterone (0.40±0.078 pmol/mg protein), and this increase was abolished by the addition of the aldosterone antagonist eplerenone (0.12±0.030 pmol/mg protein). These data suggest that the immortalized hypothalamic N1 cells secrete OLF and that aldosterone stimulates its secretion via mineralocorticoid receptors.

Validation of home blood pressure-monitoring devices, Omron HEM-1020 and Omron i-Q132 (HEM-1010-E), according to the European Society of Hypertension International Protocol.

OBJECTIVE: Allowing patients to measure their blood pressure (BP) at home is recognized as being of clinical value. However, it is not known whether BP measurement is usually taken correctly outside of a clinical setting. Automated proper wrapping of the cuff and correction of wrong posture will help in taking BP measurement properly. This study aimed to evaluate the performance of the Omron HEM-1020 and the Omron i-Q132 devices, which are equipped with those functions. METHODS: A team of three trained doctors validated the performance of these devices by comparing data obtained from both devices with those from a standard mercury sphygmomanometer. Both devices passed the validation requirements of the European Society of Hypertension International Protocol. The magnitude of the difference in BP readings between the tested device and the standard mercury sphygmomanometer was within the range of ± 3 mmHg, which is allowed by the European Society of Hypertension guidelines. CONCLUSION: Both the Omron HEM-1020 and the Omron i-Q132 devices were found to be useful for measuring BP at home because their performance fulfilled the requirement of the guidelines.

Isolation of marinobufotoxin from the supernatant of cultured PC12 cells.

1. Digitalis-like factors (DLFs) are believed to be involved in sodium metabolism via inhibition of Na(+) /K(+) -ATPase and may cause hypertension. Yet, the source and regulation of secretion of DLFs remain unknown. Recently, marinobufagenin (MBG) was isolated in mammals and implicated in renal sodium and water metabolism. More recently, we isolated marinobufotoxin (MBT), a suberoyl arginine ester of MBG, in Y-1 cells. We have developed an ELISA to measure MBG-like immunoreactivity (MBG-IR) and have characterized MBG-IR using chromatography. We have also identified a ouabain-like factor in cultured PC12 cells from a phaeochromocytoma cell line. In the present study, we examined whether MBT was produced in the adrenal medulla. 2. PC12 cells were cultured in serum-free medium and culture supernatants were collected over a period of 24 h. The supernatants were analysed by ELISA and HPLC to determine MBG-IR content. The HPLC fraction containing the main peak of MBG-IR was characterized by LC/MS. 3. Compared with samples collected at 0.5 h, the concentration of MBG-IR in culture supernatants increased significantly after 2 h and continued to increase until 24 h. The fraction with the highest ELISA peak for MBG-IR had the same HPLC elution time as authentic MBT. Furthermore, tandem mass spectrometry indicated that each fraction of MBT and MBG had the correct specific daughter ions. 4. The results indicate that MBT and MBG are produced and/or secreted by adrenomedullary cells.

A difficult diagnosis case of prolonged thrombocytopenia with sepsis and disseminated intravascular coagulation.

A 19-year-old male was admitted because of the trauma due to sepsis-induced disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). We treated with antibiotics, danaparoid, and continuous hemodiafiltration (CHDF). Once he recovered, but after several days, he had septic shock and MOF again. With treatment, the inflammation and MOF improved but the platelet count was less than 1.0 × 10( 4)/µL. Because of the usage of heparin, we suspected heparin-induced thrombocytopenia (HIT) and measured the HIT antibody and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Heparin-induced thrombocytopenia antibody was positive in the second sepsis but negative in the first sepsis. ADAMTS13 activity was low in both sepses. After stopping CHDF and the usage of heparin, his platelet count improved. Thrombocytopenia is the common and occasional condition for DIC. Heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura is rare but they must be ruled out in thrombocytopenia with nontypical clinical course, and the assays for HIT antibody and ADAMTS13 activity are useful tools.

Pitavastatin further decreases serum high-sensitive C-reactive protein levels in hypertensive patients with hypercholesterolemia treated with angiotensin II, type-1 receptor antagonists.

Lipid-lowering therapy with a statin not only powerfully lowers cholesterol but also exerts anti-inflammatory effects by decreasing serum C-reactive protein (CRP). Since an angiotensin II, type-1 receptor antagonist (ARB) also decreases CRP levels, the add-on effect of statins on CRP may be worth exploring. We determined the effect of pitavastatin on serum levels of highly sensitive CRP (hs-CRP) in 30 patients with hypercholesterolemia undergoing treatment with anti-hypertensive medication including ARBs. Pitavastatin, 2 mg daily, was given. The control group consisted of hypertensive patients without hyperlipidemia. The low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hs-CRP were measured at baseline, 1, 3, 6, and 12 months after treatment. For the atherosclerotic index, LDL-C/HDL-C ratios at 12 months were calculated. The LDL-C level was markedly reduced at 1 month and thereafter. The baseline level of hs-CRP in the hyperlipidemia group was significantly higher than that in the control group (1.647 ± 0.210 mg/L vs. 0.666 ± 0.097 mg/L p < 0.0001). After 3 months, the percentage of reduction of hs-CRP was significantly higher than that in the control group. The absolute values of hs-CRP were significantly decreased to a level similar to the control group, and the hs-CRP in both groups was remained at the same level for 12 months. Although the LDL-C/HDL-C ratios of the pitavastatin group was significantly reduced from 3.3 to 1.8, those of the control group were not changed. In conclusion, pitavastatin was found to have powerful anti-inflammatory, add-on effects over the similar effects of ARB as assessed by hs-CRP.

[Study on the diagnostic role of NT-proBNP assay for assessment of cardiac function, and the effect of renal function--comparable study with BNP].

We, in the present study, studied the stability, operability, and economy as a whole of NT-proBNP assay, and further on the performance of diagnosing cardiac failure as a laboratory test. It was found to be superior to BNP assay not only as a reagent but also as a clinical test to diagnose cardiac functions. On the other hand, it is reported that NT-proBNP is influenced by the renal function more than BNP, and we investigated it precisely. As a result, NT-proBNP was equally influenced as BNP when the estimated glomerular filtration rate (eGFR) was more than 60 ml/min. When eGFR decreased further, BNP was also increased by the decreased renal clearance. Thereby, NT-proBNP was increased relatively more than BNP because BNP was catabolized by other mechanisms than renal clearance. Therefore, NT-proBNP may be superior to BNP in regard to estimate secretion of BNP from the heart particularly when renal function was decreased. In conclusion, NT-proBNP is an excellent biomarker to diagnose heart failure.

[Case of spuriously high level of squamous cell carcinoma antigen in patient without carcinoma--HPLC and ultrafiltration are useful to analyze the true value].

Squamous cell carcinoma antigen (SCCA) is a diagnostic tumor marker for the advanced uterine, cervix and lung tumor. Although SCCA is a prognostic indicator for some tumors, recent progress of this marker has shown that the SCCA could also be found in the serum of nonmalignant disease such as renal failure and others. Here, we report a case of spuriously high level of SCCA in patient without carcinoma, renal failure, head-and-neck disease and lung disease. An early fifties female who had been undergone the diagnostic conization for high-grade cervical intraepithelial neoplasia ten years ago and observed without special treatment with around 20ng/ml level of SCCA. She has no signs of tumor, renal failure, head-and-neck disease or lung disease until now. The high performance liquid chromatography with Superdex 200 showed the molecular weight of the major part of SCCA of the patient is more than 160 kDa and the part of 45 kDa, the same molecular weight as lung tumor, is trace amount. Moreover, the ultrafiltration analysis showed the SCCA of the present case did not penetrate the 100 kDa cut-filter, but SCCAs with other patients with uterine, cervix, lung tumor and renal failure did penetrate the filter. In this case, the analysis of molecular weight of SCCA using HPLC gel filtration and ultrafiltration is useful to rule out spuriously elevated SCCA.