Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

INTRODUCTION: Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. METHODS: We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. RESULTS: The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. CONCLUSION: Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1.

Sonographic Detection of Subcutaneous Foreign Bodies in 3 Cases.

Subcutaneous masses caused by foreign bodies are frequently encountered in daily practice. Although the majority of foreign bodies such as metals can be detected by radiography, substances such as vegetative materials or wood are difficult to detect. To our knowledge, only a few studies have described the sonographic characteristics of foreign bodies. Herein, we report 3 cases where we studied the sonographic characteristics of the foreign bodies in the dermis and subcutaneous tissue. Our results revealed the following 3 foreign bodies: (1) glass, (2) vegetative material, and (3) a pencil core. Thus, sonographic examination is useful for the detection of foreign bodies.

[Effects of Aging and Sex Differences on the Median Nerve: Relationship Between Nerve Conduction Study and Ultrasonographic Cross-Sectional Nerve Area].

OBJECTIVE: The aim of this study was to evaluate the relationship between nerve conduction and sonographic measurements of the median nerve, and to investigate the effects of aging and sex on nerve structure. METHODS: Measurements from both hands of 82 healthy volunteers were included in this study (45 men and 37 women, 38.9 ?17.7 years). The cross-sectional area(CSA) of the median nerve was evaluated at the carpal tunnel inlet (MA) and at the midpoint of the forearm (MB). RESULTS: The CSA of the median nerve at the MA was significantly correlated with age (r=0.501, P< 0.001), and distal motor latency (r=0.269, P<0.001). Although this study demonstrated the effects of the sex dif- ferences and aging on the CSA of the median nerve at MA, there was no significant effect at the MB. CONCLUSIONS: Our study suggests that aging could affect median nerve structure, especially at the anatomical entrapment point. [Original].

[Change in Serum Levels of New Hepatic Fibrosis Marker "Mac-2 Binding Protein Glycosylation isomer (M2BPGi)" in Patients with Chronic Hepatitis C during the Treatment of Pegylated Interferon and Ribavirin].

The sustained virological response (SVR) rate in the patients with HCV has currently reached to 90% by the progression of anti-viral therapy. However, several reports demonstrated that hepatocellular carcinoma develops even in the patients with SVR. It is widely accepted that liver fibrosis plays a pivotal role in hepatocellular carcinogenesis. Thus, an accurate staging for liver fibrosis is necessary to improve long-term prognosis of hepatitis C patients. Recently, Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a novel hepatic fibrosis marker. In the present study, we compared the value of M2BPGi in serum before and after the anti-viral therapy in hepatitis C patients. The value of M2BPGi in patients with F2, F3, or F4 stagings was significantly higher than that in F1 staging. Moreover, the value of M2BPGi significantly decreased after the treatment with pegylated interferon plus ribavirin similarly to other liver fibrosis-related markers. In addition, the value of M2BPGi in patients with SVR was significantly decreased after the anti-viral therapy (P < 0.0001). The reduction of M2BPGi in SVR patients was thought to reflect the improvement of liver fibrosis, in conjunction with the reduction of viral load, after the treatment. In conclusion, the measurement of M2BPGi in serum might be useful in monitoring the improvement of liver fibrosis by anti-viral therapy.

Sonographic Findings of Subcutaneous Sarcoidosis in 3 Cases.

Subcutaneous sarcoidosis occurs infrequently among cases of cutaneous sarcoidosis. To our knowledge, few studies have described the sonographic characteristics of subcutaneous sarcoidosis. Here we report the sonographic characteristics of 3 cases of this condition. Our results revealed 4 features: (1) an irregular hypoechoic appearance, (2) heterogeneous echogenicity, (3) perilesional hyperechoic changes, and (4) abnormal Doppler signals. Sonography is a rapid, simple, and noninvasive procedure that is useful for initial evaluation of granulomatous lesions such as subcutaneous sarcoidosis.

[Evaluation of peripheral neuropathy in the patients with type 2 diabetes mellitus by laboratory examination: relationship between albuminuria and ankle-brachial index].

The aim of this study was to investigate the influence of peripheral neuropathy on laboratory examinations and to evaluate the relationship between nerve conduction velocity (NCV), albuminuria, and ankle-brachial index (ABI) results in patients with type 2 diabetes mellitus (DM). One hundred twenty-six patients with type 2 DM who had undertaken the nerve conduction study for an initial screening test of diabetic complications were included in our study. We divided patients to 4 groups according to the stage of microalbuminuria and ABI results. Two factors negative (2FN) group (n = 75), urinary albumin creatinine ratio (A/C) < 30 mg/gCr and ABI > or = 1.0; A/C group (n = 25), A/C > or = 30 mg/gCr and ABI > or = 1.0; ABI group (n = 14), A/C < 30 mg/gCr and ABI < 1.0; two factors positive (2FP) group (n = 12), A/C > or = 30 mg/gCr and ABI < 1.0. Neuropathy, retinopathy, hypertension, macroangiopathy, and hyperlipidemia were seen in 57.9%, 38.1%, 59.5%, 22.2%, and 56.3%, respectively. Lower leg NCV in 2FP group was significantly lower than other groups. Our study indicated that impaired diabetic peripheral neuropathy may be detected by combining decreased ABI with increased A/C results.

[Diagnostic ability of ultrasonography for the rotator cuff tear: comparison with ultrasonography and MRI findings].

Ultrasonography (US) is a non-invasive method which can assess not only solid tissue organs but also soft tissues such as tendons and nerves. However, it has not been fully understood that US is a useful tool for the depiction of periarticular structure. We compared the diagnostic accuracies between US and magnetic resonance imaging (MRI) in the patients with rotator cuff tear (RCT). Seventy patients, who underwent arthroscopic surgery, preoperative US and MRI examinations at Gifu University Hospital from January 2010 to April 2013 (49 male, 21 female, mean age 59.7 +/- 15.9) were included in this study. The diagnostic accuracy, sensitivity and specificity of US and MRI were 94.3% and 94.3%, 95.8% and 97.9%, 90.9% and 84.6%, respectively, when the intraoperative finding was regarded as a gold standard. These results suggest that US is useful for the diagnosis of RCT as equal as MRI.

[A retrospective study of the relationship between bacterial numbers from central venous catheter tip cultures and blood cultures for evaluating central line-associated bloodstream infections].

Catheter-related bloodstream infection (CRBSI) is an infectious disease requiring special attention. It is a common cause of nosocomial infections; catheter insertion into the central veins particularly increases the risk of infection (CLA-BSI: central line-associated bloodstream infection). We examined the relationship between the number of bacterial colonies cultured from shredded central venous catheter (CVC) tips and from blood cultures in our hospital from 2011 to 2012. Coagulase-negative staphylococci topped the list of microbe isolated from the CVC tip culture, followed by Pseudomonas aeruginosa, Staphylococcus aureus, and Candida spp. S. aureus and Candida spp., with growth of over 15 colony-forming units in the CVC tip culture, were also detected at high rates in the blood culture. However, gramnegative bacilli (Enterobacteriaceae and P. aeruginosa) did not show a similar increase in colony number in the CVC tip culture. Because microbes adhering to shredded catheter tips are readily detected by culture, this method is useful as a routine diagnostic test. In addition, prompt clinical reporting of the bacterial number of serious CLA-BSI-causing S. aureus and Candida spp. isolated from CVC tips could contribute to earlier CLA-BSI diagnosis.

[Clinical significance of hyaline casts in the new CKD risk classification (KDIGO 2009)].

Chronic kidney disease (CKD) significantly contributes to the increased number of dialysis patients with end stage renal disease. A new CKD risk classification (KDIGO 2009) established in 2011, which is defined by albuminuria and estimated glomerular filtration rate (eGFR) values, demonstrates the relative risks of CKD in great detail. In this study, we evaluated the clinical significance of urinary casts by categorizing a risk Group 1 to 5 according to the KDIGO 2009 classification. In the high risk CKD group (risk group 3 and over), we found a significantly higher number of patients who had > 100 hyaline casts/whole field (WF) in their urine than those that had < 100 hyaline casts/WF. Further, we determined the diagnostic accuracy for the high risk CKD group when the cutoff value for the number of hyaline casts was set at > or = 100 hyaline casts/WF (sensitivity: 44.7%, specificity: 96.5%). The eGFR value was significantly lower in the group with > or = 100 hyaline casts/WF, particularly in hypertensive patients, than that in the group with < 100 hyaline casts/ WF. Of interest is that the eGFR value was significantly lower in patients with 100-999 hyaline casts/WF and > or = 1,000 hyaline casts/WF than that in patients with < 100 hyaline casts/WF in A1 stage. Thus, our present study suggests that the presence of > or = 100 hyaline casts/WF indicates decreased eGFR, and the urinary casts counting may be important and useful for the screening and early detection of high-risk CKD.

Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients.

OBJECTIVES: Serum creatinine (Scr) is not a reliable marker of renal function in critically ill patients because of an enhancement of protein catabolism, which makes it difficult to adjust the dosage of renally eliminated drugs such as antibiotics. This study aimed to investigate whether serum cystatin C (Scys-C) could be used as a reliable marker of renal function. METHODS: We investigated whether Scys-C was a reliable marker of renal function in 56 critically ill patients. Subsequently, the usefulness of Scys-C to determine the initial loading and the maintenance dose of vancomycin was examined in 18 patients. Crea- tinine clearance (Ccr) was assessed from Scr and creatinine in urine collected over 24 h (24-h Ccr). KEY FINDINGS: There was a good correlation between 24-h Ccr and 1/Scys-C (r(2) = 0.616), whereas less marked correlation was observed between 24-h Ccr and 1/Scr (r(2) = 0.221). On the other hand, vancomycin concentration was predicted from population pharmacokinetic parameters based on a two-compartment linear model. There were significant correlations between real trough concentrations of vancomycin and the values predicted from Scys-C using various equations (r(2) = 0.416-0.488), while less pronounced relationships were observed between real concentrations and the values predicted from Scr (r(2) = 0.134-0.187). CONCLUSIONS: These findings suggest that Scys-C is a reliable marker reflecting renal function in critically ill patients and is applicable to determine the initial loading dose as well as the maintenance dose of vancomycin.

[Urinary protein to creatinine ratio and urinary sediments are useful for the screening of chronic kidney disease].

Chronic Kidney Disease (CKD) is an important risk factor of the End Stage Renal Disease (ESRD). In this study, we investigated whether the protein to creatinine ratio (the ratio of P/C) determined by the semiquantitative urinary stick test and urinary sediments are useful for the early detection of CKD. One hundred sixty patients were classified to four or five groups by P/C ratio and various biochemical markers were analyzed. As a result, the 300 mg/g x Cr of P/C group showed a significantly increased serum cystatin C level. The positive rate of the P/C ratio in CKD stage was significantly increased compared with the conventional protein qualitative analysis. Further, the amounts of urinary sediments in CKD stage 1 to 2 were increased, such as hyaline cast, and pathological casts were increased in CKD stage 3 to 5. Thus, our present study suggests that the ratio of P/C and urinary sediments are useful for the screening of CKD.

[Clinical laboratory system in a complete electronic hospital].

The use of a Laboratory Information System (LIS) and Laboratory Automation System (LAS) are clearly superior to manual results in terms of completeness and legibility. As the current clinical information system (CIS) in Gifu University Hospital consists of a complete electronic medical record system, the clinical laboratory was re-engineered to simplify workflow, pay attention to quality assurance, and decrease various costs by an intelligent laboratory management system. We named the new system Gifu Premiotic Intelligent Laboratory System (GPILS). Further advances will concentrate on the cost-effective use of LIS, and the potential use of GPILS in our laboratories will be discussed. In addition, because one of our clinical laboratories currently provides various useful clinical laboratory-oriented information to physicians and patients, we have developed new tools named the "Reference Data Base (RefDB)". In the near future, several different types of computer technology for various clinical laboratory information will lead to the development of highly specific platforms for LIS corresponding to a complete electronic medical record system.

[Clinical significance and problems in HCV measurement--comparison of CLEIA method with PCR method].

Infection of a hepatitis C virus (HCV) is confirmed by the presence of HCV antibody or HCV-RNA. Recently, a highly sensitive method to examine HCV-core antigen has been developed. In this study, to evaluate the clinical significance of HCV-core antigen determination, we examined serum HCV infection markers, HCV-core antigen, HCV-RNA (AMPLICOR) and HCV-antibody (third generation) concentrations. We determined 225 serum samples, and three patients receiving the treatment with interferon. In 102 HCV-RNA positive samples, significant correlation was observed between HCV-RNA and HCV-core antigen (r=0.734, p<0.0001). However, three out of 102 (2.9%) cases were included within the negative range of HCV-core antigen (20 fmol/l). The HCV-core antigen value in three patients receiving the treatment with interferon paralleled with the amount of HCV-RNA. The determination of HCV-core antigen by CLEIA is a useful and time-saving method, but an attention should be paid to the presence of false-negative cases.

Changes in quinolinic acid production and its related enzymes following D-galactosamine and lipopolysaccharide-induced hepatic injury.

Increases in quinolinic acid (QUIN), a neurotoxic L-tryptophan metabolite, have been observed in human serum and cerebrospinal fluid and in animal models of severe hepatic injury. The aim of this study was to evaluate the changes in QUIN accumulation and its related enzymes after acute hepatic injury induced by D-galactosamine and endotoxin. Gerbils were given an intraperitoneal injection of pyrogen-free saline alone as control, lipopolysaccharide (LPS) alone (150 ng/kg), D-galactosamine alone (500 mg/kg) or a combination of D-galactosamine with LPS. Concentrations of QUIN, its related metabolites, and related enzyme activities were determined. D-Galactosamine treatment significantly decreased activities of hepatic aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) resulting in increased QUIN concentrations in serum and tissues. The magnitude of QUIN responses was markedly increased by endotoxin due to the increased availability of L-kynurenine, a rate-limiting substrate for QUIN synthesis. Further, infiltration of monocytes/macrophages, which is a possible major source of QUIN production in the liver, was shown by immunohistochemistry after hepatic injury induced by D-galactosamine and endotoxin. Increased serum QUIN concentrations are probably due to the increased substrate availability and the decreased activity of aminocarboxymuconate-semialdehyde decarboxylase in the liver, accompanying the increased monocyte/macrophage infiltration into the liver after hepatic injury.

[The present status of convergence in PSA reference values--from the surveillance in the Tokai-Hokuriku district].

The number of patients with prostatic cancer is recently increasing in Japan and it is well known that serum PSA determination is routinely used as a tumor marker of prostatic cancer. However, the reference values of PSA are widely varied, because the reactivities of the antibody to free PSA and ACT-PSA are different in each kit. Thus, there is no compatibility among values determined by available kits. In this study, we sent a questionnaire on PSA determination to 180 hospitals with more than 200 beds. The recovery rate to the questionnaire was 80.5% (145/180) and the determination was performed in house at 47 hospitals out of 145. Stamey in Stanford University recommended to set the ratio of complex PSA to free PSA 9:1 in the reference material. It is expected that PSA ad hoc committee in Japan reported that the inter-kit variability is becoming small. It can be said that the standardization for PSA determination is progressing. To discriminate prostatic cancer from benign prostatic hypertrophy, free PSA ratio or complex ACT-PSA is recommended. Further accumulation of data on PSA will be necessary to confirm this matter.

[Clinical significance of MMP-3 in patients with rheumatoid arthritis: comparison with other inflammatory markers(IL-6, IL-8)].

We determined serum metalloproteinase-3(MMP-3) and inflammatory cytokine(IL-6, IL-8) levels in patients with rheumatoid arthritis(RA). Sera were obtained from 307 healthy subjects(female 140, male 167), 54 RA patients, and 17 osteoarthritis (OA). The MMP-3 concentrations in healthy female and male were 43.3 +/- 15.3 ng/ml and 90.7 +/- 26.0 ng/ml, respectively. The serum MMP-3 levels in male were significantly higher than those in female (p < 0.0001). MMP-3 levels in RA patients(259.1 +/- 34.2 ng/ml) were significantly higher than OA(43.6 +/- 6.1 ng/ml) or healthy controls. There was a significant correlation between MMP-3 and CRP(r = 0.586), IL-6(r = 0.345) levels in serum. In contrast, no significant correlation was observed between MMP-3 and IL-8(r = 0.19), or CA-RF(r = 0.052) levels. However, there were some cases with high MMP-3 levels in CA-RF-negative patients definitely diagnosed as RA. These findings suggest that MMP-3 determination is useful for the early diagnosis and the follow-up during the treatment for RA patients.