研究者詳細 - 杉山　大典

論文 - 杉山　大典

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Reverse remodelling induces progressive ventricular resynchronization after cardiac resynchronization therapy 'from vicious to virtuous cycle'

Matsumoto Kensuke, Tanaka Hidekazu, Okajima Katsunori, Hayashi Takatoshi, Kajiya Teishi, Sugiyama Daisuke, Kawai Hiroya, Hirata Ken Ichi

European Journal of Echocardiography 12 （ 10 ） 782 - 789 2011年10月

ISSN 1525-2167

Aims: Cardiac resynchronization therapy (CRT) can stop the vicious cycle resulting from dyssynchrony and generates left ventricular (LV) reverse remodelling. Our objective was to assess the time course and the relationship between improvement in LV dyssynchrony and reverse remodelling after CRT. Methods and results: Sixty-four consecutive patients were evaluated before, immediately after, and 3- and 6 months after CRT. We measured LV volumes, ejection fraction (EF), and sphericity index, and dyssynchrony was assessed using speckletracking radial strain. Response was defined as a >15% decrease in end-systolic volume (ESV) 6 months after CRT, and event-free survival was followed for 24 months. Responders and non-responders had similar baseline LV volumes and EF. During the first and the following 3 months after CRT, LV volumes gradually decreased (enddiastolic volume: 195±73 to 164+60* to 129±51 mL†, ESV: 141±70 to 110±47* to 82±40 mL†), and sphericity index and EF progressively increased (sphericity index: 1.52±0.20 to 1.75±0.31* to 1.94±0.34†, EF: 28±7 to 34±7* to 38±8%†, *†P < 0.001) in responders. No such changes were observed in non-responders. Furthermore, dyssynchrony diminished progressively during the first and the following 3 months after CRT and patients with progressive resynchronization experienced fewer major cardiovascular events than those without (P < 0.001). Conclusion: CRT can stop the vicious cycle of remodelling and dyssynchrony, and actually, turn it into the virtuous cycle of reverse remodelling and further resynchronization. All rights reserved. © The Author 2011.

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Plasma platelet-derived microparticles in patients with connective tissue diseases

Oyabu Chinami, Morinobu Akio, Sugiyama Daisuke, Saegusa Jun, Tanaka Shino, Morinobu Sahoko, Tsuji Goh, Kasagi Shimpei, Kawano Seiji, Kumagai Shunichi

Journal of Rheumatology 38 （ 4 ） 680 - 684 2011年04月

ISSN 0315-162X

Objective. To clarify the role of platelet-derived microparticles (PDMP), which are small vesicles with thrombotic and immunological properties, in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis/polymyositis (PM/DM), and mixed connective tissue disease (MCTD). Methods. Plasma levels of PDMP were measured by ELISA, and compared among patients with one of the 4 diseases. Association of PDMP levels with clinical characteristics and medication of the patients was also examined. Results. PDMP levels were higher in patients with MCTD and SSc than in controls. Multiple linear regression analysis revealed that patients with Raynaud's phenomenon (RP) showed higher PDMP levels than those without. PDMP levels in individual patients did not fluctuate significantly over several months. Conclusion. PDMP level is associated with MCTD, SSc, and RP, and could be a novel marker for RP. The Journal of Rheumatology Copyright © 2011. All rights reserved.

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Association of calcineurin A gamma subunit (PPP3CC) and early growth response 3 (EGR3) gene polymorphisms with susceptibility to schizophrenia in a Japanese population

Kyogoku Chieko, Yanagi Masaya, Nishimura Kunihiro, Sugiyama Daisuke, Morinobu Akio, Fukutake Masaaki, Maeda Kiyoshi, Shirakawa Osamu, Kuno Takayoshi, Kumagai Shunichi

Psychiatry Research 185 （ 1-2 ） 16 - 19 2011年01月

ISSN 0165-1781

To examine the association of PPP3CC (rs10108011 and rs2461491) and EGR3 (rs3750192) single-nucleotide polymorphisms (SNPs) with Japanese schizophrenia, we performed a case-control association study using 337 patients and 369 healthy controls. As a result, by our moderated cohort-size study, PPP3CC and EGR3 are not genetic risk factors for schizophrenia, whereas meta-analysis showed weak association of rs10108011 with schizophrenia in the Japanese population (odds ratio (OR) = 1.12, P= 0.01). © 2009 Elsevier Ireland Ltd.

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Dobutamine-induced improvement in inferior myocardial contractile function predicts reduction in functional mitral regurgitation

Tatsumi Kazuhiro, Kawai Hiroya, Sugiyama Daisuke, Norisada Kazuko, Kataoka Toshiya, Onishi Tetsuari, Tanaka Hidekazu, Hirata Ken Ichi

Circulation: Cardiovascular Imaging 3 （ 6 ） 638 - 646 2010年11月

ISSN 1941-9651

Background - Left ventricular (LV) remodeling can increase tethering force to mitral valve and functional mitral regurgitation (FMR). Because the relationship between FMR and regional myocardial function has not been quantitatively evaluated, we conducted a quantitative investigation of this association. Methods and Results-The effective regurgitant orifice (ERO) of FMR in 51 patients with depressed LV ejection fraction (32±9%) secondary to ischemic or nonischemic cardiomyopathy was compared with mitral deformation (valve and annulus), global LV remodeling (volume indices, function, and sphericity), and regional myocardial contractile function, as assessed by longitudinal peak systolic strain rate (Ssr) in LV anterior, anteroseptal, inferoseptal, inferior, inferolateral, and anterolateral segments at rest. Low-dose dobutamine (10 μg/kg per minute)-induced changes in ERO were compared with changes in the variables. Multivariable analysis identified the predictors of ERO at rest as mitral valvular tenting (β=0.062; P<0.001), Ssr in the inferior segment (inferior Ssr) (β=-0.178; P<';.001), and LV sphericity (β=0.414; P=0.001) and the predictors of valvular tenting at rest as inferior Ssr (β=1.680; P<;0.001), LV end-systolic volume index (β=0.022; P=0.001), and LV sphericity (β=3.886; P=0.012). Furthermore, dobutamineinduced reduction in ERO was predicted by reduction in valvular tenting (β=-0.087; P<;0.001) and increase in inferior Ssr (β=-0.082; P<;0.001), and dobutamine-induced reduction in valvular tenting was predicted by increase in inferior Ssr (β=-0.860; P<;0.001).Conclusions-Inferior regional myocardial dysfunction was quantitatively associated with mitral valvular tenting and FMR. Moreover, improvement with dobutamine of inferior myocardial contractile function attenuated valvular tenting and FMR. Inferior myocardial contractile function can affect the configuration of the mitral apparatus and predict FMR severity. © 2010 American Heart Association, Inc.

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Congenital cholesteatoma

Inokuchi Go, Okuno Taeko, Hata Yuko, Baba Miyuki, Daisuke Sugiyama

Annals of Otology, Rhinology and Laryngology 119 （ 7 ） 490 - 494 2010年07月

ISSN 0003-4894

Objectives: We described the characteristics of congenital cholesteatoma in Japanese patients and assessed whether the staging system is useful for predicting the rate of residual disease, the need for reexploration, and surgical outcomes. Methods: We performed a retrospective chart analysis of 23 consecutive patients with congenital cholesteatoma. Results: The proportion of cases with anterior-superior quadrant involvement was significantly lower in the Asian group than in Western patients. The total residual rate was 26%, and there was a positive association between stage and residual rate, ranging from 0% in stage ? and ?? to 44% in stage IV. Canal wall-up tympanomastoidectomy was the most frequent procedure (57%), and 61% had reexploration. Conclusions: Congenital cholesteatoma in Asia is less likely to involve the anterior-superior quadrant than in Western patients. The 4-stage system was useful for predicting residual rates, even in patients in whom anterior-superior quadrant involvement was less common. Postoperative hearing was significantly related to the stages. A routine second-look procedure may be unnecessary in the early stages, whereas reexploration would be better performed in advanced stages. Endoscopy might reduce residual disease and the need for reexploration in the near future. © 2010 Annals Publishing Company. All rights reserved.

Preoperative systolic strain rate predicts postoperative left ventricular dysfunction in patients with chronic aortic regurgitation

Onishi Tetsuari, Kawai Hiroya, Tatsumi Kazuhiro, Kataoka Toshiya, Sugiyama Daisuke, Tanaka Hidekazu, Okita Yutaka, Hirata Ken Ichi

Circulation: Cardiovascular Imaging 3 （ 2 ） 134 - 141 2010年03月

ISSN 1941-9651

Background-The best predictor for postoperative left ventricular (LV) systolic dysfunction in patients with chronic aortic regurgitation is still a matter of debate. The aim of this study was to assess the clinical significance of preoperative systolic radial strain rate (Ssr) derived from tissue Doppler echocardiography as a predictor of postoperative LV systolic dysfunction in patients with chronic aortic regurgitation. Methods and Results-In 52 patients (mean age, 58 years; 13 women) with isolated chronic aortic regurgitation, we performed standard and tissue Doppler echocardiography before and after operation, obtained echocardiographic parameters such as LV dimensions and LV ejection fraction, and measured Ssr in 4 walls of the LV. Linear regression analysis determined correlations between preoperative parameters and postoperative LV ejection fraction. Receiver-operating characteristic curve analysis assessed the optimal cutoff values of parameters that predicted postoperative LV systolic dysfunction (ejection fraction <50%). The operation caused significant decreases in LV dimensions and volumes and significant increases in Ssr (1.94±0.64 to 2.39±0.83 per second; P<0.001) and ejection fraction (53.0±8.7 to 59.0±8.8%; P<0.001). Multiple regression analysis demonstrated that averaged Ssr was the only independent predictor of postoperative LV systolic dysfunction among the covariates examined (P<0.001). Using receiver-operating characteristic curve analysis, averaged Ssr yielded the greatest area under the curve among preoperative parameters (0.80) and was indicated to be a good predictor of postoperative LV dysfunction, with 90.9% sensitivity and 73.2% specificity (cutoff value, 1.82 per second). Conclusions-Measurement of preoperative averaged Ssr is useful in predicting postoperative LV systolic dysfunction and optimizing surgical timing in patients with isolated chronic aortic regurgitation.

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Haemodynamic changes in the fingers after free radial forearm flap transfer

Yanagisawa Akira, Hashikawa Kazunobu, Sugiyama Daisuke, Makiguchi Takaya, Yanagi Hideyuki, Kumagai Shunichi, Yokoo Satoshi, Terashi Hiroto, Tahara Shinya

Journal of Plastic, Reconstructive and Aesthetic Surgery 63 （ 3 ） 539 - 543 2010年03月

ISSN 1748-6815

Harvesting the radial forearm flap may cause circulatory problems in the donor arm. To investigate the influence on donor hands after radial forearm flap harvesting, we assessed the process of circulatory changes prospectively by measuring skin perfusion pressure (SPP) that is clinically useful in detecting vascular lesions. The records of 17 patients (14 men and 3 women aged 59.7 ± 11.8 years) who had undergone free radial forearm flap transfer for head and neck reconstruction, between December 2005 and April 2007, were analysed. SPP in the thumb (finger I), the middle finger (III) and the little finger (V) was measured in the 17 patients preoperatively and 1 month and 3, 6, 9 and 12 months postoperatively. All statistical tests were two sided, with a significance level defined as p < 0.05. Preoperatively, baseline SPP was more dominant in finger I than in finger V. Postoperatively, SPP changed significantly in both fingers, while it showed no change in finger III and tended to be higher in finger I than in the other two. Harvesting the free radial forearm flap reduces skin perfusion in the fingers of the donor arm and, we assume, leads to a re-distribution of blood flow to the fingers, with the residual ulnar artery still supplying more blood flow to finger I than to finger V. This suggests the presence of an autoregulating mechanism whereby blood perfusion to the fingers is controlled by the physiological demands of individual fingers. © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons.

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Impact of smoking as a risk factor for developing rheumatoid arthritis

Sugiyama D., Nishimura K., Tamaki K., Tsuji G., Nakazawa T., Morinobu A., Kumagai S.

Annals of the Rheumatic Diseases 69 （ 1 ） 70 - 81 2010年01月

ISSN 0003-4967

Objectives: To assess whether smoking is a risk factor for developing rheumatoid arthritis (RA). Design: Meta-analysis. Method: Data sources were observational studies that examined the association between smoking history and the risk of developing RA identified through Medline and EMBASE (from 1966 to December 2006), relevant books and a reference search. Two authors independently extracted the following: authors' names, publication year, sample size, participant characteristics, odds ratios (OR) or relative risks, adjustment factors, study design and area where the study was conducted. Data syntheses were based upon random effects model. Summarised syntheses effects were expressed by OR. Results: Sixteen studies were selected from among 433 articles. For men, summary OR for ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to 2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+) RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91 (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever, current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22 (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77). Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02). Conclusion: Smoking is a risk factor for RA, especially RF+ RA men and heavy smokers.

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Serum matrix metalloproteinase-3 as predictor of joint destruction in rheumatoid arthritis, treated with non-biological disease modifying anti-rheumatic drugs

Mamehara Akira, Sugimoto Takeshi, Sugiyama Daisuke, Morinobu SAHOKO, Tsuji Goh, Kawano Seiji, Morinobu Akio, Kumagai Shunichi

Kobe Journal of Medical Sciences 56 （ 3 ） 2010年

ISSN 0023-2513

Background: Rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have been studied extensively as prognostic markers of rheumatoid arthritis (RA). However, despite the fact that matrix metalloproteinase-3 (MMP-3) is linked to RA activity, few studies have evaluated MMP-3 as prognostic marker. Objective: To evaluate the performance of MMP-3 as predictor of joint destruction in RA treated with non-biological disease modifying anti-rheumatic drugs. Methods: In a retrospective study of 58 early to moderate stage RA patients who consulted the Department of Clinical Pathology and Immunology, Kobe University Hospital between May 2002 and April 2009, we evaluated the performance of MMP-3 and other biomarkers as predictors of joint destruction, by comparing them between radiographically progressive and non-progressive group. Results: Serum levels of RF at entry and ACPA, but not MMP-3 at entry, were significantly higher for the progressive group. Ratios of patients with MMP-3 levels higher than healthy control were not significantly different for the two groups. However, cutoff values determined through receiver operating characteristic analysis showed that the ratio of patients with elevated RF was significantly higher in the progressive group (p=0.001), while MMP-3 (p=0.092), ACPA (p=0.052), CRP (p=0.056), and ESR (p=0.069) tended to be more elevated in the progressive group. Multiple logistic regression analysis using the cutoff value identified MMP-3 positive and RF positive, but not ACPA, CRP or ESR, as significant factors for radiographic progression (OR 16.79 [95% CI: 1.34-414.19]). Conclusion: MMP-3 can be a useful marker for prediction of joint destruction.

Validity and utility of cat classification system for oncological mandibular defects A multi-institutional study

Hashikawa Kazunobu, Tahara Shinya, Sugiyama Daisuke, Yokoo Satoshi, Hyodo Ikuo, Motomura Hisashi, Kubo Tateki, Kurita Tomoyuki, Yoshimoto Seiichi, Takushima Akihiko, Yamashita Tetsuro, Sakuraba Minoru, Yagihara Kazuhiro, Nakagawa Masahiro, Yano Tomoyuki, Ishida Katsuhiro, Sakurai Hiroyuki, Terao Yasunobu, Tanaka Katsumi, Kimata Yoshihiro

Toukeibu Gan 36 （ 3 ） 309 - 315 2010年

ISSN 1349-5747

Background: We have previously proposed the CAT classification system, a simple and clear-cut system for classifying segmental mandibular defects after oncological surgery: “C” refers to the loss of the condylar head of the mandible, “A” the mandibular angle and “T” the mental tubercle. Here, we report a statistical and mathematical taxonomical study on the validity and utility of the classification system. Methods: Data were collected from 17 medical institutions in Japan on 259 patients who had undergone surgical ablation and simultaneous microsurgical oromandibular reconstruction (osteocutaneous free flap or soft tissue free flap with reconstruction-plate) attributed to head and neck cancer. The mandibular defects were classified according to the CAT system and the two commonly used systems HCL and Urken, and the validity and utility of the CAT system were tested as follows: 1) the tendency among the numbers of the three reference points of the CAT system (C, A and T) and the esthetic outcome of each patient were analyzed by Jonckheere's trend test, 2) each of the classified patterns of the three systems was analyzed by cluster analysis based on the esthetic results using Ward's method. Results: 1) There was a statistically significant trend among the numbers of the three reference points in the CAT system and the esthetic outcome, 2) each of the grouped clusters in the CAT system was clinically explicable and demonstrated a significant difference in the esthetic outcome; the two other systems did not yield such information. Conclusion: The CAT classification system is valid and useful for oncological segmental mandibular defects.

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Plasma tetrahydrobiopterin/dihydrobiopterin ratio - A possible marker of endothelial dysfunction

Takeda Masafumi, Yamashita Tomoya, Shinohara Masakazu, Sasaki Naoto, Takaya Tomofumi, Nakajima Kenji, Inoue Nobutaka, Masano Tomoya, Tawa Hideto, Satomi-Kobayashi Seimi, Toh Ryuji, Sugiyama Daisuke, Nishimura Kunihiro, Yokoyama Mitsuhiro, Hirata Ken Ichi, Kawashima Seinosuke

Circulation Journal 73 （ 5 ） 955 - 962 2009年05月

ISSN 1346-9843

Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. Conclusions: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders.

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Delivery may affect arterial elasticity in women

Hashimoto Masayoshi, Miyamoto Yoshitomo, Iwai Chikao, Matsuda Yasuaki, Hiraoka Eiji, Kanazawa Kenji, Nishimura Kunihiro, Sugiyama Daisuke, Ito Kazuo, Yamori Yukio, Akita Hozuka

Circulation Journal 73 （ 4 ） 750 - 754 2009年04月

ISSN 1346-9843

Background: Estrogen is considered to be cardioprotective, but estrogen replacement therapy for postmenopausal women has not shown results for either primary or secondary cardiovascular event prevention. During normal pregnancy, women have significantly higher levels of estrogen and it may be endogenous estrogen that helps prevent atherosclerosis. Methods and Results: The present cross-sectional study examined the association between pregnancy followed by delivery and clinical atherosclerosis using the brachial-ankle pulse wave velocity (PWV). A total of 2,560 women undergoing annual health screening at the Institute of Hyogo Prefecture Health Promotion Association in Japan were recruited. Pregnancy history (the age of menarche/menopause and the number of gravida/para), conventional coronary risk factors, and brachial-ankle PWV were recorded. Multivariate linear regression by stepwise selection analysis demonstrated that women who had 1 or more deliveries had a significantly lower PWV, independent of age and other conventional coronary risk factors. Conclusions: Pregnancy followed by delivery may decrease arterial stiffness and prevent the progress of atherosclerosis in women. The contribution of such a pregnancy followed by delivery-related decrease in arterial stiffness to the reduction of cardiovascular disease in women should be further evaluated.

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Comparison of remnant lipoprotein-cholesterol measurements

Hihara Mari, Sato Itsuko, Hayashi Fujio, Sugiyama Daisuke, Kawano Seiji, Fujioka Yoshio, Ishikawa Yuichi, Kumagai Shunichi

Rinsho byori. The Japanese journal of clinical pathology 57 （ 1 ） 24 - 30 2009年01月

ISSN 0047-1860

Elevation of serum remnant lipoprotein concentration is an emerging risk factor for coronary artery disease. An immunoseparation procedure for remnant-like particle cholesterol(RLP-C) has been evaluated extensively in recent years. In addition, a new detergent-based method has been developed and applied to automated analyzer as "MetaboLead RemL-C" (RemL-C, KYOWA MEDEX CO., LTD.). Then, we compared the concentrations of remnant lipoproteins as RemL-C with those as RLP-C in various conditions. RemL-C assay was intra-assay-reproducible (n=20, CVs: 0.6-2.2%), and reproducible for 2 days in the refrigeration and for 8 hours in room temperature. This assay was also inter-assay-reproducible (during 5 days in the deep freezing, CVs: 1.6-3.0%). The available range for RemL-C assay was between 0.09 and 121.1 mg/dl. There were no detectable interferences from hemoglobin, free/conjugated bilirubin, chyle, and Intrafat. However, heparin influenced the titer of RemL-C concentrations. Correlation of values between RLP-C and RemL-C in 123 samples was excellent (r=0.924, p<0.001). However, different responses to intermediate lipoprotein fraction derived from a patients with type III hyperlipidemia were observed. In conclusion, RemL-C and RLP-C measurements may have a similar clinical significance. Differences in sensitivity for intermediate lipoprotein fraction between both methods may exist.

Lack of association between tyrosine kinase 2 (TYK2) gene polymorphisms and susceptibility to SLE in a Japanese population

Kyogoku Chieko, Morinobu Akio, Nishimura Kunihiro, Sugiyama Daisuke, Hashimoto Hiroshi, Tokano Yoshiaki, Mimori Tsuneyo, Terao Chikashi, Matsuda Fumihiko, Kuno Takayoshi, Kumagai Shunichi

Modern Rheumatology 19 （ 4 ） 401 - 406 2009年

ISSN 1439-7595

Tyrosine kinase 2 (TYK2) is a type I interferon (IFN) signaling pathway gene and was previously reported to be a risk factor for systemic lupus erythematosus (SLE) in Caucasian populations. In order to test for its genetic association with SLE in a Japanese population, TYK2 single nucleotide polymorphisms (SNPs), rs2304256, rs12720270 and rs280519, were genotyped. A case - control association study was performed in a total of 411 Japanese SLE patients and 467 healthy controls. Linkage disequilibrium (LD) among TYK2 SNPs was examined. According to the data from 94 healthy controls, non-synonymous rs2304256 resulting in Val → Phe substitution was revealed to be in a LD with rs12720270 and rs280519. Therefore, we further genotyped rs2304256 as a tag SNP in the full sample sets. As a result, no differences in genotype distribution and allelic frequencies of rs2304256 were found between SLE patients and healthy controls. In conclusion, TYK2 is not a genetic risk factor for SLE in a Japanese population. Our result suggests that there is an ethnic difference in the susceptibility genes for SLE.

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Usefulness of the formula for predicting creatinine clearance from serum cystatin C

Oyabu Chinami, Hayashi Nobuhide, Sugiyama Daisuke, Umezu Michio, Kinoshita Shouhiro, Hayashi Hiroki, Kawano Seiji, Kumagai Shunichi

Rinsho byori. The Japanese journal of clinical pathology 56 （ 12 ） 1093 - 1099 2008年12月

ISSN 0047-1860

Estimation of Glomerular filtration rate (GFR) is crucial for the detection of renal insufficiency. In clinical practice, GFR is generally estimated from Ccr by some prediction formulas including the serum creatinine concentration and some variables: age, sex, body size. It has been suggested that serum cystatin C is less influenced by sex, body size, muscular mass or inflammation. In several studies, serum cystatin C performed better than serum creatinine did as a marker to detect GFR reduction. We developed the formula for predicting creatinine clearance (Ccr) from serum cystatin C, serum creatinine and serum beta 2-microgroburin by multiple regression analysis. In this study, we analysed 24-hour Ccr and variables (sex, age and BMI) in 82 subjects with renal diseases to develop suitable formulas. Our serum cystatin C formula is as follows: Ccr (ml/min/1.73m2) = (12.14-0.03 x age-1.72 x serum cystatin C) 2. Correlation between measured 24-hour Ccr and predicted Ccr by our serum cystatin C formula was higher (r=0.852) than our serum creatinine formula (r=0.755), serum beta 2-microgroburin formula (r=0.793), Cockcroft-Gault formula (r=0.836) and Horio formula (r=0.825). Accuracy within 15% was higher (39.0%) than other formulas (25.6-30.5%). Our formula using serum cystatin C for predicting Ccr is a useful and precise marker for Ccr than other commonly used formulas using serum creatinine.

Importance of skin perfusion pressure in treatment of critical limb ischemiai

Tsuji Yoriko, Hiroto Terashi, Kitano Ikuro, Tahara Shinya, Sugiyama Daisuke

Wounds 20 （ 4 ） 95 - 100 2008年04月

ISSN 1044-7946

The authors studied whether skin perfusion pressure (SPP) measurements can be used to accurately predict wound healing in critical limb ischemia (CLI) and to select peripheral arterial reconstructive procedures. Methods. Forty-seven patients (33 men and 14 women, age 36ĝ€"83 years) with 69 ischemic limbs with foot ulcers or gangrene were studied retrospectively. Skin perfusion pressure was compared to the treatment outcomes (ulcers healed and ulcers that failed to heal). As a diagnostic test for CLI, the sensitivity, specificity, and the positive and the negative predictive values (PPV, NPV) of SPP measurement were calculated; the data was then analyzed by the receiver operation characteristic (ROC) curve. Results. According to the ROC curve, the best SPP measurement performance was at 35 mmHg. Conclusion. Wound healing at the appropriate amputation level must be predicted to minimize invasive debridement. Skin perfusion pressure measurement is useful for predicting wound healing in the presence of CLI. Skin perfusion pressure ĝ‰¥ 35 mmHg is requisite for wound healing; at SPP

Prevalence of disease-specific antinuclear antibodies in general population

Hayashi Nobuhide, Koshiba Masahiro, Nishimura Kunihiro, Sugiyama Daisuke, Nakamura Tomoko, Morinobu Sahoko, Kawano Seiji, Kumagai Shunichi

Modern Rheumatology 18 （ 2 ） 153 - 160 2008年04月

ISSN 1439-7595

The aim of this study was to investigate the types and prevalence of disease-specific antinuclear antibodies (ANAs) and their relationship to rheumatic diseases in the general Japanese population. An immunofluorescence (IF) method was used for the first screening of ANA levels in serum samples obtained from 2181 residents of a small Japanese town. Individuals positive for IF-ANA were then further tested for disease-specific ANAs using eight enzyme immunoassays. Physical status and the presence of illness were determined by means of questionnaires and medical examinations. Based on the result of the IF-ANA assay, the rates of positive samples at 1:40 and 1:160 dilutions were 26.0 and 9.5%, respectively, with females have significantly higher positivity rates than males (P < 0.0001). Among 566 IF-ANA-positive individuals, 100 individuals were found to have 114 disease-specific ANAs. Anti-SSA/ Ro, anti-centromere, and anti-U1RNP antibodies were detected in 58, 30, and 11 individuals, respectively, but anti-Sm, anti-Scl-70, and anti-Jo-1 antibodies were undetectable. Questionnaires and medical examinations revealed that among 60 disease-specific ANA-positive individuals that were available for testing, six had Sjögren's syndrome (SS), five were suspected of having SS, and five had rheumatoid arthritis. Surprisingly, 34 (57%) of the disease-specific ANA-positive individuals were clinically healthy. Anti-SSA/Ro, anti-centromere, and anti-U1RNP antibodies were quite frequent among clinically healthy Japanese subjects, although anti-Sm, anti-Scl-70, and anti-Jo-1 antibodies were not. Of the 60 individuals who tested positive for disease-specific ANAs, 30% (18/60) actually manifested systemic rheumatic diseases, while 50% showed no detectable signs or symptoms of rheumatic diseases.

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Diagnostic accuracy of serum procalcitonin concentrations for detecting systemic bacterial infection in patients with systemic autoimmune diseases

Tamaki Kenichiro, Kogata Yoshinori, Sugiyama Daisuke, Nakazawa Takashi, Hatachi Saori, Kageyama Gohichi, Nishimura Kunihiro, Morinobu Akio, Kumagai Shunichi

Journal of Rheumatology 35 （ 1 ） 114 - 119 2008年01月

ISSN 0315-162X

Objective. To examine whether serum procalcitonin (PCT) concentrations are useful for distinguishing bacterial infections from disease flares in patients with systemic autoimmune diseases. Methods. Patients with systemic autoimmune diseases who were admitted to our hospitals due to either a suspected deterioration of their primary diseases or an infectious disease were enrolled. Serum PCT levels were measured in 99 serum samples of 98 patients who had elevated serum C-reactive protein (CRP) levels; 29 samples were obtained from patients with bacterial infections, and 70 samples were obtained from patients with disease deterioration without a detectable infection. The diagnostic accuracy, sensitivity, and specificity for identifying a bacterial infection were estimated using the receiver-operating characteristic curve. Multiple logistic regression analysis was also done with PCT level, age, sex, steroid dose, and use of immunosuppressive agents. Results. Serum PCT levels were higher in the bacterial infection group than in the disease flare group (mean ± SD, 4.539 ± 9.677 vs 0.116 ± 0.127; p < 0.0001). The diagnostic accuracy of PCT for bacterial infection was 0.797, sensitivity 53.3%, and specificity 97.1%. On multivariate analysis, the odds ratio of a PCT ≥ 0.5 ng/ml was significant (OR 59.085, 95% CI 7.705-453.088, p < 0.0001) for identifying bacterial infection. Conclusion. Elevated serum PCT levels have a good specificity for diagnosing bacterial infection in patients with systemic autoimmune diseases regardless of their dosage of oral corticosteroids and immunosuppressive agents.

Overestimation of serum levels of rheumatoid factor caused by the presence of an incorrect calibrator in the Dade Behring kit

Hayashi Nobuhide, Kawano Seiji, Sugiyama Daisuke, Nishimura Kunihiro, Nakazawa Takashi, Morinobu Akio, Kumagai Shunichi

Modern Rheumatology 17 （ 5 ） 447 - 449 2007年10月

ISSN 1439-7595

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Thioredoxin may exert a protective effect against tissue damage caused by oxidative stress in salivary glands of patients with Sjögren's syndrome

Kurimoto Chiyo, Kawano Seiji, Tsuji Goh, Hatachi Saori, Jikimoto Takumi, Sugiyama Daisuke, Kasagi Shimpei, Komori Takahide, Nakamura Hajime, Yodoi Junji, Kumagai Shunichi

Journal of Rheumatology 34 （ 10 ） 2035 - 2043 2007年10月

ISSN 0315-162X

Objective. To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sjögren's syndrome (SS). Methods. Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2′-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-γ (IFN-γ) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-γ and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining. Results. Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-γ-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX. Conclusion. Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.

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杉山 大典

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杉山　大典

論文 - 杉山　大典