Yuji Sawabe

Changes in serum erythropoietin and the reticulocyte count during chemotherapy for leukemias

Abstract:  We serially determined serum erythropoietin (Epo) and the reticulocyte count in patients with various types of leukemia during chemotherapy. Serum Epo increased soon after the initiation of chemotherapy and decreased after the termination of therapy irrespective of the types of leukemia or treatment regimen. However, it did not stay at low level but fluctuated. The reticulocyte count, on the other hand, showed a transient rise while serum Epo level descended. The value of serum Epo when increased was higher than the value expected from hemoglobin concentration; this finding was similar to that in aplastic anemia. These results suggest that myelosuppression is a major factor for the increase in serum Epo level during leukemia chemotherapy.

Reducing the Incidence of Pseudohyperkalemia by Avoiding Making a Fist During Phlebotomy: A Quality Improvement Report

BACKGROUND Pseudohyperkalemia is uncommon, but important. Local release of potassium caused by contraction of the forearm muscles from a tightly clenched fist or repeated fist clenching during phlebotomy is a recognized cause of pseudohyperkalemia. We investigated the use of a standard protocol to avoid fist clenching during phlebotomy. STUDY DESIGN Quality improvement report. SETTING & PARTICIPANTS In 7 healthy volunteers, 10 blood samples were collected over 10-second intervals after 20 repeated fist clenching and unclenching movements. In 86 healthy volunteers, 3 blood samples were collected with and without prior fist clenching. Between September 1, 2006, and June 30, 2007, peripheral venous blood samples were collected from 73,846 outpatients at Chiba University Hospital without a protocol to avoid fist clenching. Between July 1, 2007, and March 31, 2009, blood samples were collected from 171,053 outpatients using the protocol. QUALITY IMPROVEMENT PLAN After July 1, 2007, blood samples were collected from the basilic or cephalic vein without making a fist or by making a fist using minimal gripping strength. Also, when multiple specimens were obtained from 1 patient, the specimen for measuring serum electrolytes was obtained after the other specimens. OUTCOMES & MEASUREMENTS Pseudohyperkalemia, defined as unexplained serum potassium level ≥6.5 mmol/L. RESULTS In the 7 volunteers, the decrease in serum potassium levels after cessation of fist clenching ranged from 8.4%-25.9%. In the 86 volunteers, the percentage with a decrease in serum potassium level ≥0.2 mmol/L between the first and third samples was 25.6% versus 6.7% with or without prior fist clenching, respectively. In clinical practice, we observed 8 cases of pseudohyperkalemia before implementing the protocol (0.0081%) and 1 case (0.00058%) after implementing the protocol (P = 0.001). LIMITATIONS Causes of hyperkalemia before using precautions were assessed using retrospective analyses. CONCLUSIONS Avoiding fist clenching during phlebotomy and not using the first specimen for electrolyte measurements when obtaining multiple specimens from a single patient can reduce the occurrence of pseudohyperkalemia.

Decreases in the serum VLDL-TG/non-VLDL-TG ratio from early stages of chronic hepatitis C: alterations in TG-rich lipoprotein levels.

Background The liver secretes very-low-density lipoproteins (VLDLs) and plays a key role in lipid metabolism. Plasma total triglyceride (TG) level variations have been studied in patients with hepatitis C virus (HCV)-related chronic hepatitis (CH-C). However, the results of these studies are variable. A homogenous assay protocol was recently proposed to directly measure the TG content in VLDL (VLDL-TG) and VLDL remnants. Methodology/Principal Findings Using the assay protocol, we determined serum VLDL-TG levels in 69 fasting patients with biopsy-proven HCV-related chronic liver disease and 50 healthy subjects. Patients were classified into stages F0–F4 using the 5-point Desmet scale. Serum total TG levels in patients with non-cirrhotic (F1–F3) CH-C did not demonstrate significant differences compared with healthy subjects, but serum VLDL-TG levels did demonstrate significant differences. Mean serum VLDL-TG levels tended to decrease with disease progression from F1 to F4 (cirrhosis). Compared with healthy subjects, serum non-VLDL-TG levels significantly increased in patients with stages F2 and F3 CH-C; however, we observed no significant difference in patients with liver cirrhosis. Furthermore, the serum VLDL-TG/non-VLDL-TG ratio, when taken, demonstrated a significant decrease in patients with CH-C from the mildest stage F1 onward. Conclusions/Significance The decrease in serum VLDL-TG levels was attenuated by increase in non-VLDL-TG levels in patients with non-cirrhotic CH-C, resulting in comparable total TG levels. Results of previous studies though variable, were confirmed to have a logical basis. The decrease in the serum VLDL-TG/non-VLDL-TG ratio as early as stage F1 demonstrated TG metabolic alterations in early stages of CH-C for the first time. The involvement of TG metabolism in CH-C pathogenesis has been established in experimental animals, while conventional TG measurements are generally considered as poor indicators of CH-C progression in clinical practice. The serum VLDL-TG/non-VLDL-TG ratio, which focuses on TG metabolic alterations, may be an early indicator of CH-C.

Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes.

Abstract Background: Diabetic nephropathy (DN) is a significant cause of hemodialysis, and its early detection is extremely important to prevent or delay end-stage renal disease. The significance of the renal function marker serum cystatin C (sCysC) and its relationship with glomerular filtration rate in chronic kidney disease (CKD) and DN in Japanese patients with type 2 diabetes remains uncertain. In this study, we examined the effectiveness of sCysC as a marker of early DN and CKD in Japanese subjects. Methods: A total of 325 Japanese patients with type 2 diabetes and 88 healthy subjects were studied retrospectively. sCysC concentration (mg/L) was determined by a latex turbidmetric immunoassay using a BioMajesty 8040 analyzer. The renal function of the diabetic patients was evaluated using the albumin-creatinine ratio (ACR) and Kidney Disease Outcome Quality Initiative-Kidney Disease Improving Global Outcomes (K/DOQI-KDIGO) classification. Results: There was a significant increase in sCysC but not in serum creatinine (sCr) or serum β2-microglobulin (sβ2M) in patients with grade 2 DN (ACR 30–300 mg/g) compared to grade 1 patients. Receiver operating characteristic analysis in grade 2 and 3 DN patients showed that sCysC had superior sensitivity and specificity than sCr and sβ2M for early detection of DN. In addition, sCysC showed particularly high sensitivity and specificity in DN patients with stage 2 CKD. Conclusions: sCysC was effective for detection of grade 2 DN and would be especially useful for screening stage 2 CKD patients (K/DOQI-KDIGO).

The abnormal reaction data-detecting function of the automated biochemical analyzer was useful to prevent erroneous total-bilirubin measurement and to identify monoclonal proteins

BACKGROUND Recently, to detect abnormal reactions and failures of the device in biological analysis, a reaction data monitoring system has been provided for automated biochemical analyzers. We investigated the usefulness of this function for total-bilirubin (T-Bil) measurement in routine testing. METHODS Abnormal reactions of T-Bil were detected in the reaction data over time based on the following items: whether the absorbance variance after mixing of the first reagent and sample exceeds the cut-off value. RESULTS In the cases in which the abnormal reaction was observed, the absorbance rapidly rose because of turbidity after mixing the sample with Reagent-1. The measured value was higher than the actual T-Bil level, for which the analyzer showed a warning mark with the output data. When this particular serum sample was subjected to immunofixation electrophoresis, the presence of a monoclonal protein was confirmed. We encountered seven similar cases out of 30,731 samples. CONCLUSIONS The reaction data monitoring system of the automated biochemical analyzers was useful to prevent false reports (misdiagnosis) due to unpredictable problems during T-Bil measurement. It was also suggested that detection of false reaction with a reagent may be a clue to find a new pathology, such as monoclonal gammopathy.

Serum erythropoietin values and serum iron status during chemotherapy for leukemia

To the Editor: In a recent paper (l), a correlation between serum erythropoietin (Epo) levels and reticulocyte counts during chemotherapy was shown. We have also found that changes in serum iron level are similar to those in Epo level. We studied 10 patients with acute leukemia, one with chronic myelogenus leukemia and one with macroglobulinemia. These patients underwent various treatments with multiple chemotherapeutic agents. Serum Epo was measured with an enzyme immunoassay (2) and serum iron and unsaturated iron binding capacity (UIBC) were measured with a colorimetric method in which a chelating agent 2-nitro-S-(N-propyl-N-sulfopropylamine) phenol was

Accelerated oligosaccharide absorption and altered serum metabolites during oral glucose tolerance test in young Japanese with impaired glucose tolerance

Impaired glucose tolerance (IGT) is a subtype of prediabetes, a condition having high risk for development to diabetes mellitus, but its pathophysiology is not fully understood. In the present study, we examined metabolic changes in IGT by using two types (D‐glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with emphasis on serum incretins and metabolites.

Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library

The present study was planned to identify novel serum antibody markers for digestive organ cancers. We have used screening by phage expression cloning and identified novel fourteen antigens in this experiment. The presence of auto-antibodies against these antigens in serum specimens was confirmed by western blotting. As for auto-antibodies against fourteen antigens, AlphaLISA (amplified luminescence proximity homogeneous assay) assay was performed in the sera of gastrointestinal cancers patients to confirm the results. Serum antibody levels against these fourteen recombinant proteins as antigens between healthy donors (HD) and esophageal squamous cell carcinoma (ESCC) patients, gastric cancer (GC), or colon cancer (CC) were compared. The serum levels of all fourteen auto-antibodies were significantly higher in ESCC and GC than those of HD. Among those auto-antibodies, except ECSA2 and CCNL2, were also detected significantly higher levels in CC than those of HD. Receiver operating curve (ROC) revealed similar results except CCNL2 in CC. AUC values calculated by ROC were higher than 0.7 in auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, HS3ST1, TUBA1B, TACSTD2, AKR1C3, BAMBI, DCAF15 in ESCC, auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, TACSTD2, AKR1C3, BAMBI, DCAF15 in GC, and auto-antibodies against TPI1, HOOK2, PUF60 in CC. AUC of the combination of HOOK2 and anti-p53 antibodies in ESCC was observed to be as high as 0.8228. Higher serum antibody levels against ten antigens could be potential diagnostic tool for ESCC. Higher serum antibody levels against eight antigens could be potential diagnostic tool for GC, and serum antibody levels against three antigens could be potential diagnostic tool for CC.

Development of a simple indocyanine green measurement method using an automated biochemical analyser

Background The indocyanine green retention rate is important for assessing the severity of liver disorders. In the conventional method, blood needs to be collected twice. In the present study, we developed an automated indocyanine green method that does not require blood sampling before intravenous indocyanine green injections and is applicable to an automated biochemical analyser. Methods The serum samples of 471 patients collected before and after intravenous indocyanine green injections and submitted to the clinical laboratory of our hospital were used as samples. The standard procedure established by the Japan Society of Hepatology was used as the standard method. In the automated indocyanine green method, serum collected after an intravenous indocyanine green injection was mixed with the saline reagent containing a surfactant, and the indocyanine green concentration was measured at a dominant wavelength of 805 nm and a complementary wavelength of 884 nm. Results The coefficient of variations of the within- and between-run reproducibilities of this method were 2% or lower, and dilution linearity passing the origin was noted up to 10 mg/L indocyanine green. The reagent was stable for four weeks or longer. Haemoglobin, bilirubin and chyle had no impact on the results obtained. The correlation coefficient between the standard method (x) and this method (y) was r=0.995; however, slight divergence was noted in turbid samples. Conclusion Divergence in turbid samples may have corresponded to false negativity with the standard procedure. Our method may be highly practical because blood sampling before indocyanine green loading is unnecessary and measurements are simple.

Estimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese patients with Graves׳ disease.

Glomerular filtration rate (eGFR) by serum creatinine (eGFRCr) or standardized cystatin C (eGFRCysC) were estimated in Japanese patients with Graves׳ disease (GD) of different sex. Clinical samples were collected from patients with GD with normal renal function to accurately validate eGFRCr and eGFRCysC levels and evaluate how hyperthyroidism affects renal function. Levels of eGFRCr and eGFRCysC showed clinical usefulness in successfully treated euthyroid patients with GD regardless of sex. The article includes detailed experimental methods and data used in our analysis. The data relates to the “Paradoxical effect of thyroid function on the estimated glomerular filtration rate by serum creatinine or standardized cystatin C in Japanese Graves’ disease patients” (Suzuki et al., 2015) [1]