Osaka City University Hospital Research Articles

Preoperative Evaluation of the Petrosal Vein With Contrast-Enhanced PRESTO Imaging in Petroclival Meningiomas to Establish Surgical Strategy

The present detailed radiological study investigated the relationship between petroclival meningiomas and petrosal veins with contrast-enhanced (CE) principles of echo-shifting with a train of observations (PRESTO) imaging to assess the potential contribution of the findings to the surgical strategy. Fourteen patients (13 women and 1 man) with unilateral petroclival meningiomas underwent microsurgical resection at Osaka City University Hospital between April 2009 and February 2011. Preoperatively, patients were examined using computed tomography (CT) and magnetic resonance (MR) imaging, including CE PRESTO imaging, focusing on the relationship between the tumor and the petrosal vein, and compared to the sensitivity of three-dimensional CT (3D-CT) venography or conventional MR imaging, including CE MR venography and constructive interference in steady-state (CISS) MR imaging. In 11 of 14 cases, we could identify the petrosal veins with intraoperative findings. In 10 of these 14 cases, the anatomical relationship between the tumor and the petrosal vein was detected preoperatively with CE PRESTO imaging, compared to 5 of 14 cases with 3D-CT venography, 5 of 14 cases with CE MR venography, and only 4 of 14 cases using CISS MR imaging. CE PRESTO imaging compares favorably to other approaches. There was no venous complication related to the surgery in any of the cases. CE PRESTO imaging is a non-invasive and useful method to assess the status of the petrosal vein in patients with petroclival meningiomas.

189P - Reduced CYP2D6 Function Potentiates the Gefitinib-Induced Rash in Patients with Non-Small Cell Lung Cancer

ABSTRACT Background Rash, liver dysfunction, and diarrhea are known as adverse events of erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportion of adverse events compared to those with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib and not of erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events between in the gefitinib and erlotinib therapies. Methods The frequency of each adverse event was evaluated during the period that the patients received EGFR-TKI therapy. CYP2D6 phenotypes were determined from the CYP2D6 genotype using real-time polymerase chain reaction methods, which are able to determine single nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of adverse events with each factor, including CYP2D6 activities as well as treatment types. Results Patients were identified through a query of patient information for subjects prospectively enrolled in the Medical Information System within Osaka City University Hospital between January 1999 and February 2012 that tracks all of the patients referred for CYP2D6 sequencing from our hospital. A total of 232 patients received gefitinib therapy, and 86 patients received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR 0.44, 95% confidence interval [CI] 0.21-0.94, p = 0.03), and not of diarrhea ≥ grade 2 (OR 0.49, 95%CI 0.17-1.51, p = 0.20) and liver dysfunction ≥ grade 2 (OR 1.08, 95%CI 0.52-2.34, p = 0.84) in gefitinib cohort. No associations were observed between any adverse events in erlotinib cohorts and CYP2D6 phenotypes (rash: OR 1.77, 95%CI 0.54-6.41, p = 0.35; diarrhea: OR 1.08, 95%CI 0.21-7.43, p = 0.93; and liver dysfunction: OR 0.93, 95%CI 0.20-5.07, p = 0.93). Conclusions CYP2D6 may relate to the metabolism of gefitinib and not of erlotinib. CYP2D6 phenotypes are one of promising factors for the development of rash in gefitinib therapy. Disclosure All authors have declared no conflicts of interest.

190P - Increase of Plasma Adiponectin Levels and Decrease of Pro-Inflammatory Cytokines in Non-Small Cell Lung Cancer Patients Treated with EGFR-TKIS

ABSTRACT Background Malnutrition in non-small cell lung cancer (NSCLC) is associated with advanced stage of disease and is needed for careful choice of treatment. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are routinely used for the treatment of advanced NSCLC with EGFR active mutations, which are promising the excellent responses. Recently, pro-inflammatory cytokines have been proposed as mediators of cancer cachexia. Adipose tissue produces and release substances called adipokines which include tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, and resistin. Adiponectin suppresses the secretion of inflammatory cytokines such as IL-8, TNF-α, and induces the secretion of anti-inflammatory cytokines such as IL-10. It has been hypothesized that EFGR-TKI therapy may affect this adipokine network. Methods The prospective study which evaluated correlations between the pre and post-treatment point of days 30 plasma adipokines and cytokines after EGFR-TKIs administration and clinical outcomes in advanced NSCLC was conducted at Osaka City University Hospital. Plasma adipokines and cytokines were analyzed by Luminex 200 PONENT system (Milliplex MAP kits; Millipore). Results A total of 33 patients were enrolled. We obtained plasma samples for analyses 33 patients on pre-treatment point, and 23 patients on days 30 point. Plasma adiponectin level on the pre-treatment point (40.34 ± 32.00ng/ml) was significantly lower than those on days 30 point (45.07 ± 26.38ng/ml, p = 0.01). On the pre-treatment point of plasma IL-8 (16.70 ± 16.01pg/ml), IL-10 (13.06 ± 29.69pg/ml), insulin (656.9 ± 514.6pg/ml) levels were significantly higher than those on days 30 point (7.154 ± 5.674 pg/ml p = 0.02; 11.53 ± 30.92pg/ml, p = 0.04; and 551.4 ± 520.2pg/ml, p = 0.02, respectively). The levels of leptin and resistin had no significant changes between pre and on days 30 points. Conclusions The EGFR-TKIs treatment for NSCLC increased the plasma adiponectin levels and decreased the plasma insulin, IL-8 and IL-10 levels. Increase of adiponectin levels by EGFR-TKIs may resolve the inflammation and increase insulin sensitivity with reduced output of insulin. Disclosure All authors have declared no conflicts of interest.

235 - Correlation of C609T Polymorphism of Nadph Quinone Oxidoreductase 1 and Hematological Toxicities in Lung Cancer Patients Treated With Amrubicin

ABSTRACT Background Amrubicin hydrochloride (AMR) is a novel synthetic aminoanthracycline derivative, that is metabolically activated to amrubicinol (AMR-OH) by carbonyl reductase. The cytotoxic activity of AMR-OH is promising for small cell lung cancer and considered as a key agent. NADPH Quinone Oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that metabolizes the quinone structures contained in both AMR and AMR-OH. NQO1 expression genotyped homozygous for minor alleles (T/T) was low compared with homozygous for major alleles (C/C) or heterozygous (C/T). We hypothesized that NQO1 C609T polymorphisms may relate to the AMR pharmacokinetics and clinical outcomes. Methods The patients with lung cancer received AMR at a dose of 30 or 40mg/m2/day on day 1-3 at Osaka City University Hospital were enrolled. Plasma sampling was performed at the time points of 24h after the third AMR injection. The concentrations of AMR and AMR-OH were determined by HPLC method. NQO1 C609T polymorphism was assayed using real-time polymerase chain reaction methods. Results A total of 35 patients were enrolled. The C/C, C/T, and T/T were observed in 12 (34.3%), 16 (45.7%), and 7 (20%) patients, respectively. A dose of 30 mg/m2 was administered to 19 patients, and 40mg/m2 was administered to 16 patients. The mean plasma concentrations of AMR-OH on day4 at a dose of 30mg/m2 and 40mg/m2 were 11.02 ± 3.83 and 16.18 ± 6.17 ng/ml, respectively (p = 0.005). In patients with AMR at a dose of 40mg/m2, the plasma concentrations of AMR-OH on day4 exhibited a tendency toward a relationship with NQO1 genotypes with values of C/C 20.5 ± 5.89, C/T 15.9 ± 5.43, and T/T 11.2 ± 4.47ng/ml (p = 0.066). The C/C was related to decrease changes in WBC, hemoglobin, and platelet counts (p = 0.01, p = 0.03, and p = 0.0005, respectively). No significant correlations were observed between NQO1 genotypes and clinical outcomes at a dose of 30mg/m2. Conclusions NQO1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities. NQO1 genotype appears to be the candidate biomarker of hematological toxicities of AMR treatment at a dose of 40mg/m2. Disclosure All authors have declared no conflicts of interest.

Immunogenicity of influenza A(H1N1)pdm09 vaccine and the associated factors on lowered immune response in patients with hepatitis C

Background Patients with underlying disease represent a high‐risk group for influenza‐associated complications and hospitalization. However, few studies investigated the immunogenicity of influenza vaccine in patients with liver disease. Objective To examine immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with liver disease and to explore the associated factors on lowered immune response. Patients/Methods A single subcutaneous dose of monovalent inactivated unadjuvanted split‐virus influenza A(H1N1)pdm09 vaccination was performed in 80 patients with chronic hepatitis C virus infection at Osaka City University Hospital in Japan. To measure the hemagglutination inhibition antibody titer, serum samples were collected before and 3 weeks after vaccination. Results No serious adverse events were observed. After vaccination, antibody titers ≥1:40 were observed in 56 patients (71%). The corresponding seroconversion proportion was 72%, and the mean fold rise was 10·3. Immune responses were robust regardless of severity of liver disease or existence of probable cirrhosis. However, patients with older age, lower body mass index, or receiving Stronger Neo‐Minophagen C tended to show lower antibody responses to A(H1N1)pdm09 vaccine. In addition, reduced immune responses were observed in patients who had received the 2009/10 seasonal vaccination prior to A(H1N1)pdm09 vaccination. Conclusions Single dose of A(H1N1)pdm09 vaccine achieved a sufficient level of immunity among patients with chronic hepatitis C. Antibody response may be affected by age, body mass index, Stronger Neo‐Minophagen C administration, and recent seasonal influenza vaccination.

Efficacy and feasibility of neoadjuvant chemotherapy with FEC 100 followed by weekly paclitaxel for operable breast cancer.

Sequential administration of anthracyclin and taxane for neoadjuvant chemotherapy (NAC) is the standard treatment for operable breast cancer. The pathological complete response (pCR) is a significant predictor of overall survival (OS), regardless of treatment. In this study, the pCR rate was retrospectively examined and compared with the treatment efficacy and the characteristics of pCR patients were analyzed. A total of 54 female patients with operable breast cancer, treated with FEC 100 followed by weekly paclitaxel between December 2005 and May 2009 at the Osaka City University Hospital, Osaka, Japan, were retrospectively reviewed. A total of 21 patients (39%) achieved pCR. The overall response rate was 91%. Only one patient had progressive disease. The pCR rate was significantly higher in those patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors and in those patients who completed the treatment course. An NAC regimen incorporating FEC 100 followed by weekly paclitaxel is effective for treating operable breast cancer.

Abstract 3396: Predictive value of metastatic lymph node ratio in diagnosis of recurrence after surgical resection of gastric cancer

Abstract Peritoneal meatastasis is the most important pattern in postoperative recurrence of gastric cancer. The purpose of this study was to investigate the predictive factors of peritoneal recurrence in gastric cancer patients who underwent surgical resection. We retrospectively analyzed clinical data of 137 consecutive patients diagnosed with peritoneal recurrence after curative gastrectomy at Department of Osaka City University Hospital. We evaluated association of clinicopathological features with relapse free survival rate. Parameters analyzed in this study included age, sex, tumor diameter, histological type, tumor infiltration, number of lymph node metastasis, TNM stage, lymphatic invasion, venous invasion, and metastatic lymph node ratio (MLR). Median survival time of entire patients was 12 months and mean MLR was 34%. For statistical analysis, we divided patients into two groups based on relapse free survival time. 78 patients who had peritoneal recurrence within one year after gastrectomy were defined as early recurrence group. The remaining 59 patients were stratified to late recurrence group. In comparison of both groups, univariate analysis showed statistically significant predictive factors associated with recurrence, for example, peritoneal lavage cytology, lymphatic invasion, tumor diameter, number of lymph node metastasis, and MLR. In multivariate analysis, MLR was identified as an independent predictive factor. Also the patients with 20% or higher MLR had poorer prognosis in overall survival. We demonstrated that lymph node metastasis was associated with peritoneal recurrence. Our findings suggested that MLR should be considered for postoperative adjuvant therapy to impede progression of peritoneal metastasis for gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3396. doi:1538-7445.AM2012-3396

Epidemiology of Lung Cancer

Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) have been proposed to have a mutual developmental mechanism, but their association has not been fully understood. We aimed to examine the association of the mutational landscape of NSCLC with co-morbid COPD.A total of 197 surgical specimens of early stage NSCLC were retrospectively collected from two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013. COPD and its severity were defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system. For molecular profiling of NSCLC patients with COPD, the extracted DNAs were deep-sequenced using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes. Logistic regression analysis was performed to evaluate the impact of COPD on the somatic mutations.The COPD group (n = 77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases. The non-COPD group (n = 120) had 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology. The frequency of PIK3CA mutation was significantly higher in the COPD group than in the non-COPD group (10.4% vs. 1.7%, p = 0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with no difference in the frequency between the two groups (17.2% vs. 17.0%). In the multivariate logistic regression model with consideration for COPD status, age, smoking dose, pathological stage, and histology, significantly more PIK3CA mutation was observed in the presence of COPD (odds ratio = 5.31, 95% CI: 1.03–27.29, p = 0.046).PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology.

A Multi-institutional Descriptive Study on the Methods of Subject Recruitment for Clinical Trials

Objectives: In this study, we surveyed the methods of subject recruitment used in medical institutions and investigated the appropriate methods for each type of clinical study or medical institution.Methods: We conducted a questionnaire survey regarding the methods of subject recruitment used in four medical institutions (Department of Clinical Research, National Cerebral and Cardiovascular Center; Clinical Trial Center, Shiga University of Medical Science Hospital; Center for Drug & Food Clinical Evaluation, Osaka City University Hospital; Translational Research Center, Kyoto University Hospital) in November 2009. We listed the methods of subject recruitment indicated in the responses and determined the suitability for specific target diseases or medical institutions based on the possibility of increasing the number of subjects or promoting registration of subjects.Results: Different methods aiming at facilitating recruitment were used depending on the target disease and the situation of the medical facility. These methods include advertising within the institution using audiovisual materials, putting information of the study on a web page, forming a volunteer group, and explaining the clinical study separately from outpatient consultation.Conclusion: It is necessary to select and combine methods of subject recruitment depending on target disease and situation of the medical facility.

Abstract 3294: The impact of occult nodal metastasis on the recurrence of esophageal squamous cell carcinoma

Abstract Esophageal cancer (ESC) is an aggressive disease with a poor overall prognosis. Survival rate of patients with cStage II/III ESC who underwerrt surgical resection have been improved, whereas half of these patients frequently caused recurrences. It has been thought that the lymph node metastasis was deeply related to the relapse of ESC. However, clinical signification of micrometastases in lymph nodes remain unclear because of complexity in the procedure to detect micrometastasis. Here we report that the impact of micrometastasis in lymph nodes on the recurrence of ESC. The aim of this study was to confirm the relation between noccult nodal metastasis and recurrence of in resected cStage II/III ESC. A total of 98 patients with ESC resected at Osaka City University hospital between January 2000 and January 2007 were targeted. Micrometastasis was investigated with one-level cytokeratin immunohistochemistry(IHC)and routine histological assessment by hematoxylin-eosin sections. Judgment of micrometastasis was done with discovery of cluster cells. Uni-and multivariate analyses of the independent recurrect facters were performed using the Cox proportional hazards regression model. A total of 6,172 lymph nodes(average 63) were examined from 98 patient, also 140 lymph nodes of micrometastasis(average 1.4) were detected. The micrometastasis was not possible to detect with routine histological assessment by hematoxylin-eosin sections. A clear difference of detected micrometastasis between relapse patients(45 patients,83%) and no relapse patient(15patients,34%) was admitted. In univariate analyses, curability(p=0.000),v facter(p=0.046),pN facter(p=0.026),pM facter(p=0.016),pStage(p=0.002),total metastatic lymph node count(p=0.000),total metastatic lymph node count added micrometastasis(p=0.000) were recurrence facters. In multivariate analyses, total metastatic lymph node count added micrometastasis were independent recurrence facters(Hazard ration 13.059,p=0.000) finally. Therefore, the number of total metastatic lymph nodes with micrometastasis have pivotal impact on the recurrence of ESC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3294.

Evaluation of Palmtop-Sized Blood Cell Counter

As point-of-care testing becomes a popular form of clinical testing, the demand for compact devices and test tools has been increasing. A prototype "Palm LC," a palmtop-sized white blood cell (WBC) counter that has been developed for point-of-care testing of clinical hematology was evaluated. The Palm LC was downsized to palmtop size using Micro Electro Mechanical Systems. Its microelectrode cartridge and reagent vial are disposable to prevent infection. As a result of reproducibility tests, the coefficient of variation was 4.6% in healthy normal sample (mean value, 4.01 × 1000/μL). The coefficient of variations for samples with abnormally low and high WBC (mean values, 0.52 and 22.24 × 1000/μL) were 40.4% and 4.4%, respectively. Linearity test results showed a 13.7% linearity error in the range of 0.5 to 118.15 × 1000/μL and 8.5% in the range of 2.2 to 27.3/μL. The regression equation for the assayed value against expected value was log(y) = 0.937 × log(x) + 0.053, and the SE regression was 0.036. In the low WBC range, results were slightly higher than expected, and in the high WBC range, they were slightly lower. Correlation with the XE-2100 (Sysmex, Kobe, Japan) was studied in 2 hospitals, and a regression analysis was carried out. The result from Tenri Hospital gave a regression equation of log(y) = 0.913 × log(x) − 0.004 (R2 = 0.887) and an SE of 0.071. Result from Osaka City University Hospital gave a regression equation of log(y) = 1.096 × log(x) − 0.175 (R2 = 0.846), and the SE was 0.058. These results will be used in marketing model development.

The prevalence of metabolic syndrome in Japanese renal transplant recipients

The prevalence of metabolic syndrome (MS) after renal transplantation has yet to be elucidated. In the present study, we investigated the prevalence of MS in Japanese renal transplant recipients. A cross-sectional study was conducted to determine the prevalence of MS in 101 renal transplant recipients at Osaka City University Hospital. The prevalence of MS was determined using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria (modified and original) and the International Diabetes Federation (IDF) criteria. Using the modified (Japanese) NCEP criteria, a total of 24 out of 101 patients (23.8%) had MS including 21 out of 64 male patients (32.8%) and three out of 37 female patients (8.1%). Using the modified (Asian) NCEP criteria, MS was diagnosed in 23 patients (22.8%); 19 male (29.7%) and four female (10.8%). Using the original NCEP criteria, MS was diagnosed in 15 patients (14.9%); 12 male (18.8%) and three female (8.1%). Using the IDF criteria, MS was diagnosed in 16 patients (15.8%); 15 male (23.4%) and one female (2.7%). The prevalence of MS differed according to the NCEP criteria used, which had different cut-off points for waist circumference (14.9-23.8%). By the IDF criteria, which cites central obesity as an essential component, the prevalence of MS was slightly lower. Furthermore, in our study, MS was more prevalent in male renal transplant recipients.

Efficacy of azithromycin administration in prevention of respiratory tract infection after bronchoscopic biopsy: A randomized, controlled trial

Respiratory tract infection is a serious complication associated with bronchoscopic biopsy. This study attempted to examine its incidence and determine an efficacious therapy for preventing such infections. Nine hundred and thirty patients who underwent bronchoscopic biopsy in Osaka City University Hospital outpatient clinic were enrolled in the study. All patients were randomly assigned to receive a 3-day course of azithromycin (500 mg/day), cefcapene pivoxil hydrochloride (300 mg/day) or no antibiotics. The primary outcome was the incidence of respiratory tract infection after bronchoscopic biopsy among the three groups. In the no-treatment group, nine of the 310 patients (2.9%) had respiratory tract infection after bronchoscopic biopsy. All patients with infection had abnormal bronchoscopic findings. Of the patients with respiratory tract infection, 60% were in the no-treatment group, 26.7% in the cefcapene group and 13.3% in the azithromycin group. Although not statistically significant, the incidence in the azithromycin group (0.7%) was lower than in the no-treatment group (P = 0.06). Among the patients with abnormal bronchoscopic findings, the incidence in the azithromycin group was significantly lower than that in the no-treatment group (3.0% vs. 14.8%; P = 0.02). Moreover, maximum C-reactive protein values also appeared to be lower in the azithromycin group than in the no-treatment group and the cefcapene group. A 3-day course of azithromycin administration is well tolerated and effective in preventing infection post bronchoscopy.

Does alcohol increase the risk of hepatocellular carcinoma among patients with hepatitis C virus infection?

We conducted a hospital-based case-control study to investigate the effects of alcohol drinking on hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) infection, with special reference to the disease course and changes in drinking habits. From among 1159 HCV-RNA positive patients under clinical follow-up at Osaka City University Hospital (OCUH), we identified 73 cases newly diagnosed with HCC during the past 3 years and selected 253 matched controls without HCC. The odds ratios were calculated for cumulative and average daily ethanol consumption, during three different periods (lifetime, before, and after the first identification of liver disease), using a logistic regression model. Among all subjects, there was a trend towards an inverse association between HCC and lifetime ethanol consumption (P=0.059-0.066). The tendency was similar for ethanol consumption before the first identification of liver disease, while no associative trend was indicated after the first identification. Among those with minor changes on abdominal ultrasonography findings at the first OCUH visit, a positive association was suggested for ethanol intake after the first identification, although results were not statistically significant. In conclusion, our results did not demonstrate a strong positive association between alcohol drinking and HCV-related HCC in this population.

Associations between physical activity, peripheral atherosclerosis and bone status in healthy Japanese women

The aim of this cross-sectional study was to investigate whether physical activity and bone status may affect arterial thickening and stiffening in healthy Japanese women. Healthy women ( n = 149; mean age, 54 years) were recruited from those who participated in a local health check program at the Osaka City University Hospital. Physical activity was assessed by physical functioning score of SF-36, and bone status by bone mineral density (BMD) in lumbar spine and calcaneus osteo-sono index (OSI). Arterial wall thickening assessed by intima–media thickness (IMT) in common carotid artery (CA) and femoral artery (FA), and arterial wall stiffening by peak wave velocity (PWV) in heart–carotid (hc) and heart–femoral (hf) as central segment and in heart–brachial (hb) and femoral–ankle (fa) as peripheral segment, respectively. By Spearman Rank correlation, lumbar spine BMD was correlated negatively with CA IMT ( ρ = −0.225, p < 0.05) and FA IMT ( ρ = −0.215, p < 0.05), and calcaneus OSI with FA IMT ( ρ = −0.330, p < 0.0001) but not CA IMT ( ρ = −0051, p = 0.5335). Both lumbar spine BMD and calcaneus OSI correlated negatively with PWV in all segments (all p < 0.05). Physical functioning score correlated weakly but significantly in a negative manner with all PWV segments (all p < 0.05) but not IMT. Multiple regression analyses revealed a significant association of calcaneus OSI ( β = −0.240, p = 0.0039) but not lumbar spine BMD ( β = −0.067, p = 0.4541) with FA IMT, although neither lumbar spine BMD nor calcaneus OSI was associated with CA IMT. Furthermore, physical functioning score was independently associated with hb and fa PWV but not hc and hf PWV, suggesting the preferential association with peripheral segment including lower extremities. Neither lumbar spine BMD nor calcaneus OSI was associated with any segment of PWV. In conclusion, it was suggested that calcaneus OSI might be associated with arterial wall thickening preferentially in femoral artery, and that physical activity may be associated with arterial wall stiffening in peripheral segment including lower extremity but not in central segment in healthy Japanese women.

高齢者における糖尿病性腎不全の進行予測因子の検討

To investigate the factors in the progression of renal failure in type 2 diabetes in elderly people. The subjects were 2034 patients hospitalized for type 2 diabetes therapy at Osaka City University Hospital from 1993 to 2000. Among them, 362 patients had diabetic non-dialyzed renal failure. Moreover, 93 patients reached the endpoint of doubling primary serum creatinine values. We analyzed the factors of progression for diabetic renal failure, and divided the cohorts into two groups. One group consisted of patients 65 years old or more (higher age group, HP), and the other of patients under 65 years old (lower age group, LP). We used the Kaplan-Meier methods and Cox proportional hazard models for the analysis of the cohorts with the endpoint of doubling the serum creatinine values. There were no significant differences between HP and LP by the Kaplan-Meier methods for progression of renal failure. According to Cox monofactorial-analysis, hypoalbuminemia was determined to be a significant factor in the progression of renal failure in both HP and LP. In the Cox multifactorial-analysis, hypoalbuminemia was a independent significant factor in HP, but not in LP. Hypoalbuminemia is considered to be a significant factor in the progression of renal failure in type 2 diabetes regardless of age, and may be a more significant factor in elderly people.

Significance of intima-media thickness in femoral artery in the determination of calcaneus osteo-sono index but not of lumbar spine bone mass in healthy Japanese people.

The aim of this cross-sectional study was to investigate whether physical activity and local arterial thickening may affect bone metabolism. To analyze the effects of physical activity and atherosclerosis on bone in healthy Japanese people, health-related quality of life (HRQL) and local arterial thickening were assessed by means of the Medical( )Outcomes Study 36-item Short Form (SF-36), and intimal-medial thickness (IMT) in common carotid artery (CA) and femoral artery (FA), respectively. Bone mineral density (BMD) in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. Healthy subjects (106 male and 154 female) were recruited from those who participated in a local health check program at the Osaka City University Hospital. A significant correlation existed between lumbar spine BMD and calcaneus OSI (r=0.551, P<0.0001). Among various scores in SF-36, only physical functioning score correlated weakly but significantly in a positive manner with lumbar spine BMD (rho=0.156, P=0.0147) and calcaneus OSI (rho=0.190, P=0.0024). Lumbar spine BMD correlated negatively with FA IMT (rho=-0.191, P=0.0027) whereas calcaneus OSI with FA IMT (rho=-0.199, P=0.0014). Multiple regression analyses revealed a significant association between FA IMT and calcaneus OSI, whereas lumbar spine BMD did not correlate significantly with FA or CA IMT. When subjects were restricted to female, FA IMT, but not CA IMT, still showed tendency against independent factors negatively associated with calcaneus OSI. Furthermore, lumbar spine BMD, but not calcaneus OSI, was weakly but significantly associated with increased physical functioning score independently. In conclusion, it was suggested that physical activity may affect bone strength in lumbar spine and calcaneus and that FA IMT might be a significant determinant of bone strength in calcaneus, but not in lumbar spine, in healthy Japanese subjects.

Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function.

This case-control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. Basal CCA IMT was significantly higher in hypothyroid patients [0.635 +/- 0.018 (mean +/- SE) mm] than in control subjects (0.559 +/- 0.021 mm, P < 0.005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0.552 +/- 0.015 mm (P < 0.0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = -0.472, P= 0.0031), low-density lipoprotein (LDL) cholesterol (r = -0.441, P= 0.0076) and the total/HDL cholesterol ratio (r =-0.435, P= 0.0057), but not with any of the other variables measured except for age (r = -0.353, P= 0.0296). This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients.

頭位および頭位変換により誘発されるめまいを主訴とする症例の検討

The canal repositional procedure (CRP) significantly relieves paroxysmal sym-ptoms of benign paroxysmal positional vertigo (BPPV), and accurate diagnosis of BPPV as well as identification of the site of the debris improves the efficacy of the therapy. However, BPPV is not only cause of positional vertigo, other diseases could also cause positional vertigo. We studied 248 patients admitted to our department at Osaka City University Hospital with the positional vertigo, to determine the frequency of BPPV and other lesions. Of these, 143 (57.7%) had peripheral lesions and 105 (42.3%) had evidence of central lesions. BPPV was found in 87 (35%), 5 of these BPPV cases were associated with central lesions. Physicians must be aware that it may be difficult to distinguish central lesions from BPPV on the symptoms.

The Second Generation of the Laboratory Information System and the Laboratory Automation System in Osaka City University Hospital

The first total clinical laboratory system (TCLA) in the Osaka City University Hospital was introduced in 1993. After six years of operation, it was recently replaced by a new system. The goals of this replacement were as follows: 1. Improve the analytical performance. 2. Make the system operate more efficiently. 3. Improve the quality of laboratory analyses. We successfully reduced the labor required to operate the laboratory; made the laboratory reports quicker; reduced the number of retraction and revalidation of the results; and minimized the system downtime.