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Ischemic compression is a manual therapy technique for myofascial pain. This study aimed to verify the effect of ischemic compression performed by family caregivers on myofascial pain syndrome (MPS) in patients and on the family's care burden.This multicenter, open-label, randomized, comparative study included patients with myofascial pain and their family caregivers who were randomized into the following groups: ischemia compression (performed by a family caregiver), sham ischemia compression, or untreated control. The effectiveness and safety of ischemic compression and the burden on family caregivers were evaluated. The primary endpoint was the rate of 50% or more improvement in the patient's mean numerical rating scale pain score in the previous 24 hours, 14 days after starting the intervention. The secondary endpoint was the rate of change in the family caregivers' reaction assessments.A total of 75 patients and caregivers (70 patients with cancer and family caregivers) who received home medical care were enrolled at three facilities. The study completion rate was 94.7%, and there were no adverse events. The rate of 50% or more improvement in the numerical rating scale score was 64.0% in the ischemic compression group, 16.0% in the sham ischemic compression group, and 4.0% in the control group (P0.001). Caregivers' self-esteem was significantly lower in the ischemic compression and sham ischemic compression groups than in the control group. However, there was no significant difference between the two groups (P=0.370).Ischemic compression for myofascial pain in patients performed by family caregivers can increase the analgesic effect in patients and self-esteem in family caregivers.The University Hospital Medical Information Network Clinical Trials Registry (approval number: UMIN000036605).

Background/Aims: Aortic arch calcification (AoAC) is a fatal complication in dialysis. AoAC progression-related molecules in continuous ambulatory peritoneal dialysis (CAPD) remain unclear. Methods: AoAC was estimated using plain chest radiography scoring (AoACS) in 30 CAPD patients (age 49.3 ± 13.4 years). AoAC progression was defined as increased AoACS on follow-up chest X-ray at the end of the study (progressors). Fibroblast growth factor-23 and osteoprotegerin (OPG) were measured. Results: Median follow-up was 38.5 months. Progressors were older, had shorter PD vintage, higher body mass index, and higher serum OPG levels (255.6 ± 109.2 pg/mL) than nonprogressors (183.4 ± 68.2 pg/mL; p = 0.0400). Progressors also showed higher pulse pressure (62.4 ± 20.0 mm Hg) and pulse wave velocity (1,909.9 ± 310.6 cm/s) than nonprogressors (48.5 ± 13.6 mm Hg; p = 0.0030 and 1,390.1 ± 252.8 cm/s; p = 0.0005, respectively). Conclusion: AoAC progression was associated with increased aortic stiffness. OPG may be associated with AoAC progression in CAPD.

Carnitine deficiency is a common condition in hemodialysis patients. Therefore, abnormalities in fatty acid metabolism and organic acid metabolism are also common in dialysis patients. Tandem mass spectrometry is a standard technique in pediatric and neonatal medicine. However, it could be a new powerful tool in other fields for estimating the state of intracellular fatty acid metabolism.Tandem mass spectrometry has recently revealed the relationships between carnitine profile and dialysis patients' anemia, reduced physical function, and survival rate. Fatty acid and organic acid metabolism, which could previously only be evaluated qualitatively, can now be quantitatively assessed. Key Message: The applications of tandem mass spectrometry are expected to expand not only in the field of dialysis but also in clinical medicine in general.

Background Carnitine deficiency is a common condition in hemodialysis patients. Therefore, abnormalities in fatty acid metabolism and organic acid metabolism are also common in dialysis patients. Tandem mass spectrometry is a standard technique in pediatric and neonatal medicine. However, it could be a new powerful tool in other fields for estimating the state of intracellular fatty acid metabolism. Summary Tandem mass spectrometry has recently revealed the relationships between carnitine profile and dialysis patients' anemia, reduced physical function, and survival rate. Fatty acid and organic acid metabolism, which could previously only be evaluated qualitatively, can now be quantitatively assessed. Key Message: The applications of tandem mass spectrometry are expected to expand not only in the field of dialysis but also in clinical medicine in general.

Serum ferritin is one of the most important and widely used markers of iron metabolism, and is a recommended standard index of iron dynamics in guidelines for renal anemia in many countries. However, serum ferritin measurement has several disadvantages. For example, it is prone to being influenced by underlying disease, and there is considerable systematic bias among different methods of measurement.Systematic bias affects not only the measurement results, but also the therapeutic strategy to be used in accordance with the relevant guidelines, and consequently the cost of medical treatment. Key Messages: Manufacturers should reduce variability in their serum ferritin assay kits. Researchers should take into account propagation of error in the analysis of measurement values, and clinicians should evaluate laboratory data with care.

The older dialysis population is growing, and malnutrition and wasting syndrome are great concerns in this population. The management of these syndromes includes appropriate nutritional intake and physical activity. However, whether management in the form of an increase in protein intake has a beneficial effect on muscle mass has not been demonstrated. In this study, we investigated an association between changes of normalized protein catabolic rate (nPCR), as a proxy for protein intake and percent creatinine generation rate (%CGR), as a proxy for muscle mass in patients receiving hemodialysis. Multiple linear regression models were employed, and we included several sensitivity analyses. The results showed that increases in nPCR were associated with increases in %CGR. The association was stronger in patients with baseline %CGR levels below 100%. This was the first study to demonstrate that an increase in dietary protein intake might increase the muscle mass, but this study had certain limitations. Future interventional studies will be needed to investigate whether increases in protein intake have a beneficial effect on sarcopenia, protein-energy wasting, and frailty.

Background Serum ferritin is one of the most important and widely used markers of iron metabolism, and is a recommended standard index of iron dynamics in guidelines for renal anemia in many countries. However, serum ferritin measurement has several disadvantages. For example, it is prone to being influenced by underlying disease, and there is considerable systematic bias among different methods of measurement. Summary Systematic bias affects not only the measurement results, but also the therapeutic strategy to be used in accordance with the relevant guidelines, and consequently the cost of medical treatment. Key Messages: Manufacturers should reduce variability in their serum ferritin assay kits. Researchers should take into account propagation of error in the analysis of measurement values, and clinicians should evaluate laboratory data with care.

The older dialysis population is growing, and malnutrition and wasting syndrome are great concerns in this population. The management of these syndromes includes appropriate nutritional intake and physical activity. However, whether management in the form of an increase in protein intake has a beneficial effect on muscle mass has not been demonstrated. In this study, we investigated an association between changes of normalized protein catabolic rate (nPCR), as a proxy for protein intake and percent creatinine generation rate (%CGR), as a proxy for muscle mass in patients receiving hemodialysis. Multiple linear regression models were employed, and we included several sensitivity analyses. The results showed that increases in nPCR were associated with increases in %CGR. The association was stronger in patients with baseline %CGR levels below 100%. This was the first study to demonstrate that an increase in dietary protein intake might increase the muscle mass, but this study had certain limitations. Future interventional studies will be needed to investigate whether increases in protein intake have a beneficial effect on sarcopenia, protein-energy wasting, and frailty.

Key Clinical Message Herpes simplex virus 2 caused a genital ulcer, and a secondary herpetic whitlow appeared during acyclovir therapy. The secondary and recurrent whitlow isolates were acyclovir-resistant and temperature-sensitive in contrast to a genital isolate. We identified the ribonucleotide reductase mutation responsible for temperature-sensitivity by deep-sequencing analysis.

OBJECTIVE: Clinically, the ankle-brachial blood pressure index (ABI) and skin perfusion pressure (SPP) are used to screen for subclinical peripheral artery disease. However, the association between the SPP and mortality in hemodialysis patients has not been previously reported. We investigated these factors and compared the ABI and SPP in patients receiving hemodialysis. METHODS: A total of 102 patients receiving maintenance hemodialysis were enrolled in this study. The ABI was determined using an ABI-form (Colin, Japan). The SPP was measured using a SensiLase(TM) PAD3000 (Kaneka, Osaka, Japan). RESULTS: The mean follow-up period was 3.2 ± 1.4 years. A multivariate Cox analysis identified a low ABI (p=0.019) and a low SPP (p=0.047) as being independent predictors of mortality. A receiver operating characteristic (ROC) analysis of the ABI revealed a cutoff point of 1.1 and an area under the curve (AUC) of 0.79, with a sensitivity of 90% and a specificity of 62%. A ROC analysis of the SPP revealed a cutoff point of 54.0 mmHg and an AUC of 0.71, with a sensitivity of 55% and a specificity of 84%. CONCLUSION: Both low ABI and SPP values were found to be independent risk factors for mortality among hemodialysis patients. The cutoff point for ABI as a predictor of mortality was 1.1, while that for SPP was 54.0 mmHg.

Frequently, focal segmental glomerulosclerosis (FSGS) recurs after renal transplantation, resulting in poor graft survival. Pathological mechanisms of the recurrence are still unknown, but both B and T cell disorders are suspected based on much evidence. This supports theoretical benefits using plasma exchange (PE) and lymphocytapheresis (LCAP). A renal transplant was performed for a 35-year-old woman, who suffered steroid-resistant FSGS and developed to chronic kidney disease stage 5D at 31 years old. We treated the patient with recurrent FSGS by LACP and examined whether peripheral neutrophils were dynamically changed after the therapy. Further, we performed flowcytometric analysis to examine lymphocyte fractions before and after LCAP. The decrease of helper (CD4 positive) and memory (CD4 and CD45RO positive) T cells was prominent after LCAP. Although B cells were at the nadir because of rituximab treatment, LCAP also decreased peripheral B cells. These suggest that LCAP has the potential to suppress the activities of recurrent FSGS after renal transplant.

We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain.

Although hepatitis C virus (HCV) infection is a persistent public health concern in hemodialysis patients, there seem to have been only a few reports on the prevalence of HCV at the start of hemodialysis. In this study we investigated whether patients starting on hemodialysis therapy are positive for anti-HCV antibody or not. The 400 patients who began regular hemodialysis between February 2003 and June 2007 were enrolled in this study. Clinical data such as age, anti-HCV antibody and primary cause of end-stage kidney disease (ESKD) were examined. As healthy controls we used 70,717 healthy blood donors in 2005 whose data were obtained from Tokyo Metropolitan Red Cross Blood Center. Anti-HCV antibody was used as an indicator of HCV infection. Since the prevalence of HCV infection is affected by age in Japan, we classified the patients by age group. The anti-HCV antibody prevalence rate among the patients who were new to hemodialysis was 7.3%, as opposed to 0.15% in the healthy volunteers. The prevalence of HCV in the 31–45-, 46–60-, and 61-year-old groups was significantly higher among the hemodialysis patients than among the healthy volunteers (P = 0.0209

目的：血液透析患者の発熱は腎不全に伴う内部環境変化と透析療法に伴う合併症の影響により，特有な病態を呈しており，しばしば原因の同定に苦慮する場合がある．慢性腎臓病患者において透析の有無や透析歴で原因不明の発熱の原因を検討した報告は少なく，今回，慢性腎臓病患者において，血液透析の有無によって発熱の原因に違いがないか，血液透析患者の発熱に対し留意する点がないかを検討した．方法・対象：当院に原因不明の37℃以上の発熱で1998年8月から2007年7月まで入院した100例を対象とした．入院精査によって得た診断名をchronic kidney disease (CKD) stage分類に基づき分類し発熱の原因を比較した．また，血液透析患者に関しては発熱の原因と透析歴の関連について検討した．結果：CKD stage5Dの患者42例は全例血液透析患者であった．発熱の原因としては，29例が感染症で，6例が透析アミロイドーシス，2例が悪性腫瘍，1例が薬剤性，4例が不明のままであった．一方，CKD stage1～5の患者58例のうち39例が感染症，9例が膠原病，3例が悪性腫瘍，1例が薬剤性で6例が不明のままであった．発熱の原因として膠原病は血液透析患者ではそのほかのCKD stageの患者に比較し有意に低率であった（0％ vs. 18.4％，p＝0.0094）．透析アミロイドーシスと診断した症例の透析歴は平均23.1±5.0年（16～29年）であり，ほかの原因による発熱に比較し透析歴が長期であった（p＜0.0001）．感染症のうち，塗抹，培養，核酸増幅法によって結核と診断した症例が血液透析患者に2例認めたのに対し，ほかのCKD stageの患者では認めなかった．結語：血液透析患者において原因不明の発熱を認めた際，まず頻度が多く，治療が遅れた場合，致命的となりうることから感染症を疑うべきである．さらに結核の可能性，また透析歴の長い場合は透析アミロイドーシスに注意が必要である．

症例1は29歳の女性. 1歳5か月にオルニチントランスカルバミラーゼ欠損症と診断された. 以後, 感染や疲労・ストレスで高アンモニア血症 (100～300μg/dL) をきたし入退院を繰り返していた. 平成13年3月23日, 嘔気があり当院外来を受診. アンモニア345μg/dLと上昇を認めL-アルギニン20g/日の点滴を施行した. しかし, 意識障害の改善なくアンモニア536μg/dLと上昇を認めたため血液濾過透析 (HDF) を施行した. 2日間のHDF施行でアンモニア72μg/dLと低下, 意識障害の改善を認めた. その後, 安息香酸ナトリウムの内服でアンモニアの上昇, 意識障害の出現なく退院となった. 症例2は筋緊張性ジストロフィーの28歳, 女性. 歩行困難, 脱力, 意識障害で入院となった. 入院翌日のアンモニアは717μg/dLと上昇し昏睡状態, 呼吸不全となった. 肝不全の所見なく原因不明の高アンモニア血症に対しHDFを施行した. 3日間のHDF施行でアンモニア40μg/dLに低下し意識状態の改善を認めた. 入院後の血漿アミノ酸分析により高シトルリン血症を認め, 成人発症2型シトルリン血症と診断した. L-アルギニンと安息香酸ナトリウムの投与を開始し, アンモニアの上昇, 意識障害の出現なく退院となった. 尿素サイクル異常症による昏睡を伴う高アンモニア血症にはL-アルギニンの経静脈投与が施行されている. 本症例のように急性期にL-アルギニンの投与が無効な症例, 昏睡を伴う原因不明の高アンモニア血症の症例には急性血液浄化の施行が有効と考えられた.

Recent data demonstrated that CD4+CD25+ regulatory T (Treg) cells and an enzyme called indoleamine 2,3-dioxygenase (IDO) mediate maternal tolerance to the fetus. Interestingly, Treg cells express the CTLA-4 molecule on their surface, and B7 (CD80/86) ligation by CTLA-4 enhanced IDO activity of dendritic cells (DCs) and monocytes by the induction of interferon gamma (IFN-gamma) production. In this study, we studied the IDO expression on peripheral blood monocytes and decidual monocytes or DCs after treatment with CTLA-4/Fc fusion protein or IFN-gamma using flow cytometry. IDO expressions on both peripheral blood DC and decidual DC and monocytes were up-regulated during normal pregnancy. On the other hand, both IDO expression on DC and monocytes after IFN-gamma treatment or CTLA-4 treatment were decreased in spontaneous abortion cases. The expression of CD86 on peripheral blood and decidual monocytes and DC in spontaneous abortion cases was lower compared with those in normal pregnancy subjects. Also, IFN-gamma production by decidual and peripheral blood mononuclear cells after CTLA-4/Fc treatment in spontaneous abortion cases was significantly lower than those in normal pregnancy subjects. These data suggest that CTLA-4 on Treg cells up-regulates IDO expression on decidual and peripheral blood DC and monocytes by the induction of IFN-gamma production.

PROBLEM: To examine whether the NK1/NK2/NK3/NKr1 paradigm can be adapted in natural killer (NK) cells. METHOD OF STUDY: Mononuclear cells were isolated from peripheral blood and/or decidua in healthy non-pregnant women (n= 17), early pregnant women (6-12 weeks of gestation, n = 17) and miscarriage cases (6-11 weeks of gestation, n = 10). We investigated the production of transforming growth factor (TGF)-β, interleukin (IL)-4, IL-5, IL-10, IL-13, interferon (IFN)-γ and tumor necrosis factor-α from peripheral blood- and decidual-CD56 b r i g h t NK cells and -CD56 d i m NK cells by flow cytometry. RESULTS: In the peripheral blood of the non-pregnant subjects, the main populations of CD56 b r i g h t NK cells and CD56 d i m NK cells were IFN-γ-producing NK1 type cells. Populations of IL-10-producing NKr1 type cells in peripheral blood CD56 b r i g h t NK cells and CD 5 6 d i m NK cells in early pregnant women were significantly greater compared with those in non-pregnant women, and these cells population decreased in miscarriage cases. In the early pregnancy decidua, the main populations of CD56 b r i g h t NK cells and CD56 d i m NK cells were TGF-β-producing NK3 type cells, and NK1 type cells were rare. NK3 type cells in decidua were significantly decreased in miscarriage cases compared with those in normal pregnant subjects. IL-4-, IL-5- or IL-13-producing NK2 type cells were rare in peripheral blood and decidua. CONCLUSION: These data support the NK1/NK2/NK3/NKr1 hypothesis. NKr1 type cells in peripheral blood and NK3 type cells in decidua might play some important roles in the maintenance of pregnancy by regulation of maternal immune function.

Acyclovir and less frequently, vidarabine are (or have been) used in the treatment of varicella-zoster virus (VZV) infection and are administered either intravenously (vidarabine) or orally (acyclovir, up to five times per day). The pharmacological bases of the administration interval were modeled in vitro in this study. Incubation of VZV-infected cultures with acyclovir or vidarabine for 24, 48, 72 and 96h showed similar duration-dependent anti-viral activities as assessed by a plaque-reduction assay. Treatment with vidarabine for only 8h/day for 4 days (intermittent treatment) showed anti-VZV activity equivalent to that of continuous treatment for 4 days in terms of the inhibitory dose that reduced plaque formation by 50% (IC(50)). In contrast, intermittent treatment with acyclovir exhibited a 7.9 times higher IC(50) value than that of continuous treatment. The mode of inhibition of expression of most of viral protein was similar in both drugs, but the degree of inhibition was different for each protein. Thus, vidarabine with a limited period of treatment showed anti-VZV activity comparable to continuous treatment with acyclovir, indicating the longer duration of anti-viral activity of vidarabine.

Background/Aim: It has been suggested that higher levels of parathyroid hormone (PTH) are required to maintain normal bone turnover in chronic hemodialysis (HD) patients. Serum PTH levels determined by intact PTH (i-PTH) assay may overestimate the actual activity of circulating PTH in HD patients. The aim of the present study was to assess the clinical usefulness of whole PTH assay on the evaluation of bone turnover in HD patients. Materials and Methods: We performed measurement of parameters on bone turnover in 179 HD patients (116 men, 63 women; mean age 61.0 ± 13.1 years). Serum whole PTH levels were determined as cyclase-activating PTH (CAP) by an immunoradiometric assay, and compared with those of i-PTH. Cyclase-inactivating PTH (CIP) was calculated as (i-PTH-CAP). The correlations between serum whole PTH levels and clinical parameters such as serum levels of Ca, P, bone alkaline phosphatase (BAP), bone Gla protein (BGP), total protein (TP), albumin (Alb), urea nitrogen (SUN), and creatinine (Cr) were analyzed using multivariate analysis. Results: The mean values of i-PTH and CAP were 124.1 ± 97.4 and 86.9 ± 71.6 pg/ml, respectively, indicating that the serum CAP levels were about 70% of i-PTH levels. The serum CAP levels significantly correlated with that of i-PTH (r = 0.959, p < 0.001). Moreover, a significant positive correlation between serum CAP levels and metabolic bone markers such as BAP (r = 0.400, p < 0.01) and BGP (r = 0.481, p < 0.01) was observed. Stepwise multivariate analysis revealed that serum levels of CAP were significantly determined by serum levels of Ca, P, Alb, and oral dosage of vitamin D (F ratio = 18.81, adjusted r2 = 0.302). Conclusions: These data suggest that the biological activity of circulating PTH in HD patients is lower than the levels estimated by conventional i-PTH assay.

A thermophile which degrades poly( l -lactic acid) (PLA) film was isolated from 153 soil samples with an enrichment culture technique at 60 °C. Under this temperature condition, the strain grew on PLA and the dissolved total organic carbon (TOC) concentration in the medium changed according to the growth stage, i.e., after the TOC rapidly reached the minimum, it increased gradually and then decreased again thereafter. As for residual PLA, viscosity number decreased rapidly but weight decreased initially slowly. Gel permeation chromatograms of the residual PLA showed a shift of the whole peak to low molecular weight region, which suggested the occurrence of degradation to the inside of the solid sample. The strain has high specificity for PLA, and the culture broth did not show esterase activity. It was identified as a neighboring species to Geobacillus thermocatenulatus, which has an optimum growth temperature of around 60 °C.

Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.

End-stage renal failure (ESRD) induces a clinical state of immunodeficiency with a higher incidence of infections and a higher mortality due to infectious complications compared with the normal population. Using a newly developed immunofluorescent staining of intracellular cytokines for flow cytometric analysis, we studied Th subsets in 22 healthy control subjects, 28 patients with compensated chronic renal failure (CRF), 25 patients on hemodialysis (HD), and 24 patients on continuous ambulatory peritoneal dialysis (CAPD). Our results demonstrate that the percentage of both interferon-γ-positive cells and interleukin-4-positive cells increased in compensated CRF patients compared with those in healthy subjects. Moreover, a significantly higher percentage of CD4-positive cells is characterized by a Th1-type cytokine production pattern in HD patients and by a Th2-type cytokine secretion pattern in CAPD patients. These results suggest that the altered Th1/Th2 balance may be associated with the pathogenesis of ESRD.

血液透析 (HD) を施行した全身性エリテマトーデス (SLE) 16例 (女性15例, 男性1例), 年齢は24-47歳の臨床像, 治療, 予後について検討した. 腎生検は, 14例に施行し12例がび漫性ループス腎炎 (LN) であり, 2例は膜性LNであった.これらの患者を腎不全の進行状態から, A, BおよびCの3群に分類した. A群 (n=6) はrapidly progressiveとした. SLEおよびLN発症より透析導入までの期間は短く進行性に腎不全に至った. 導入時, CH50は低値で免疫学的活動性は高く, 治療も大量のステロイド剤投与を行い, 全例血漿交換療法の併用, 3例でステロイドパルス療法も施行していた. 治療後は, 免疫学的異常と腎機能の改善を認めた. B群 (n=3) は, acute on chronicであった. A群に準じた治療を行いHD離脱したが, 1例が早期に急死した. 他の2例が再導入となった. C群 (n=7) は, chronicとした. SLEあるいはLN発症よりHD導入までの期間が最長240か月, 180か月の症例もあり, LNが慢性の経過で腎不全に至った群である. 6例の腎組織型はいずれもび漫性LNであり, 全例高血圧を認め, 糖尿病も2例に合併していた. 導入時のCH 50で評価するSLEの免疫学的活動性はA群に比し低く (p

Deoxydative acetoxylation of 3-methoxy-, 3-phenyl-, 3-methyl-, 3-chloro-, and 3-methoxycar-bonylpyrazine 1-oxides furnished predominantly 2-acetoxy-6-substituted pyrazines, some of which were more selectively prepared by addition of zinc bromide and triethylamine to the reaction. Regioselectivity of the acetoxylation is discussed based upon heat of formation by AMI and AMI-COSMO for all possible isomers of each set.

Azidopyrazines bearing amino, methoxy and/or phenyl groups have been synthesized by reaction of pyrazine N-oxides with trimethylsilyl azide in the presence of diethylcarbamoyl chloride in refluxing acetonitrile. In most cases, the azidation occurs only at the carbon α to the N-oxide function, and 3-substituted pyrazine 1-oxides gave 2-azido-3-substituted pyrazines. Conversely, methyl, chloro and methoxycarbonylpyrazine N-oxides did not undergo azidation. The electronic and steric effects of the substituent on the reactivity are discussed.

Deoxydative acetoxylation of 3-methoxy-, 3-phenyl-, 3-methyl-, 3-chloro-, and 3-methoxycar-bonylpyrazine 1-oxides furnished predominantly 2-acetoxy-6-substituted pyrazines, some of which were more selectively prepared by addition of zinc bromide and triethylamine to the reaction. Regioselectivity of the acetoxylation is discussed based upon heat of formation by AMI and AMI-COSMO for all possible isomers of each set.

The insidious onset and occult characteristic of psoas abscess can cause diagnostic delays, resulting in high mortality and morbidity rates. Here, we investigated the characteristics of psoas abscess in hemodialysis patients.This study was carried out in eight patients with psoas abscess who were admitted in our hospital. The clinical data were retrospectively collected.The frequency of polycystic kidney disease as the primary cause of end-stage kidney disease was significantly higher in the hemodialysis patients with psoas abscess (25.0%) than in prevalent Japanese hemodialysis patients (3.4%, P = 0.028). All patients had a preceding infection (discitis in two, blood access-related infections in two, colitis in two, infection of a hematoma in the kidney in one, and endocarditis in one). Seven patients survived, while the remaining one patient died.Psoas abscess could be a complication of discitis, blood access infection and colitis in hemodialysis patients. The frequency of polycystic kidney disease as the primary cause of ESKD was significantly higher in the hemodialysis patients with psoas abscess than in prevalent Japanese hemodialysis patients. We should consider psoas abscess as a possibility in hemodialysis patients with infection of unknown cause, especially in patients with polycystic kidney disease.

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin treatment. The cellular iron status of the patients can be determined from the recently available measurement of reticulocyte hemoglobin equivalent (RET-He). RET-He is measured on the basis of automated fluorescent flow cytometry which in the reticulocyte channel, using a polymethine dye, also measures the mean value of the forward light scatter intensity of mature red blood cells and reticulocytes. These values equate with reticulocyte hemoglobin content. In this study, to clarify the accuracy of RET-He in diagnosing iron deficiency in dialysis patients, we initially compared RET-He with such iron parameters as serum ferritin levels, transferrin saturation and content of reticulocyte hemoglobin (CHr) which has been established as indicators of functional iron deficiency. Secondly, we investigated the changes in RET-He during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 217 haemodialysis patients. Iron deficiency was defined as havsing a transferrin saturation (TSAT) < 20% or serum ferritin < 100 ng/ml. Conventional parameters of red blood cells and RET-He were measured by on a XE-2100 automated blood cell counter (Sysmex). CHr was measured on an ADVIA120 autoanalyser (Siemens). RET-He mean value was 32.4 pg and good correlation (r = 0.858) between RET-He and CHr is obtained in dialysis patients. Receiver operating characteristic curve analysis revealed, values of the area was 0.776 and at a cutoff value of 33.0 pg, a sensitivity of 74.3% and a specificity of 64.9%, were achieved. Iron supplements given to the patients with low TSAT or ferritin, RET-He responded within 2 weeks, and this seemed to be a potential advantage of using RET-He in the estimation of iron status. RET-He is a new parameter, equivalent value to CHr, and is easily measurable on the widely spread and popular blood cell counter and is a sensitive and specific marker of iron status in dialysis patients.

A consensus conference for the Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Dialysis Patients was conducted in the general meeting of the Japanese Society for Dialysis Therapy (JSDT) in June 2006, and the guidelines were proposed in the Journal of JSDT in 4 months later. The aim of this study was performed on the status of observance with the data, based on 6 months later proposal of the guidelines. Only 48.9% stayed within the range specified by the calcium and phosphorus guideline. Moreover, only 12% of patients were able to remain within the ranges specified by all three guidelines (calcium, phosphorus, and PTH), 6 months later proposal of the guidelines. In our institution, compliance with the JSDT guidelines was inadequate. Major reasons were the special characteristics of the medical care system and patients in our institution as a university hospital. Further improvement in the contents and method of the use of the guidelines is necessary alongside observation of the present situation in Japan.

A statistical survey of 3932 nationwide hemodi- alysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not neces- sarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arte- rial blood HCO 3- . Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally max- acalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact par- athyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D pre- paration decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%. Key Words: Calcium carbon- ate, Death rate, Intact parathyroid hormone, Sevelamer hydrochloride.

A statistical survey of 3750 nationwide dialysis facilities was carried out by the Japanese Society for Dialysis Therapy (JSDT) at the end of 2003, with answers to the questionnaires received from 3717 facilities (99.12%). The population of dialysis patients in Japan at the end of 2003 was 237,710, and the number of dialysis patients per million people was 1862.7. The crude death rate during a 1-year period from the end of 2002 to the end of 2003 was 9.3%. The mean age of patients newly introduced to dialysis was 65.4 years, and the mean age of the entire dialysis population was 62.3 years. The primary diseases in the patients newly introduced to dialysis in 2003 included diabetic nephropathy (41.0% of patients) and chronic glomerulonephritis (29.1% of patients). The mean serum neutral fat concentration for all the dialysis patients was 113.9 +/- 71.7 mg/dL (+/- SD). The mean serum low density lipoprotein (LDL)-cholesterol concentration was 90.8 +/- 30.9 mg/dL. Dialysate calcium concentrations ranging from 3.0 mEq/L to less than 3.5 mEq/L were used for majority of the dialysis patients (55.4%). Among anticoagulants given to the dialysis patients, heparins were the most commonly used in 79.3% of the dialysis patients. The relationship between blood pressure during dialysis and life expectancy for 1 year was analyzed for 43,465 patients who had undergone dialysis three times per week at the end of 2001. Results showed a significantly high mortality risk for patients who had systolic blood pressure of less than 100 mm Hg at the start of dialysis, systolic blood pressure of less than 100 mm Hg at the end of dialysis, and the greatest decrease (lowest) in systolic blood pressure of less than 120 mm Hg during dialysis. Patients who received vasopressor therapy during dialysis had a higher mortality risk than those who received no vasopressor therapy.

To examine whether the NK1/NK2/NK3/NKr1 paradigm can be adapted in natural killer (NK) cells.Mononuclear cells were isolated from peripheral blood and/or decidua in healthy non-pregnant women (n = 17), early pregnant women (6-12 weeks of gestation, n = 17) and miscarriage cases (6-11 weeks of gestation, n = 10). We investigated the production of transforming growth factor (TGF)-beta, interleukin (IL)-4, IL-5, IL-10, IL-13, interferon (IFN)-gamma and tumor necrosis factor-alpha from peripheral blood- and decidual-CD56bright NK cells and -CD56dim NK cells by flow cytometry.In the peripheral blood of the non-pregnant subjects, the main populations of CD56bright NK cells and CD56dim NK cells were IFN-gamma-producing NK1 type cells. Populations of IL-10-producing NKr1 type cells in peripheral blood CD56bright NK cells and CD56dim NK cells in early pregnant women were significantly greater compared with those in non-pregnant women, and these cells population decreased in miscarriage cases. In the early pregnancy decidua, the main populations of CD56bright NK cells and CD56dim NK cells were TGF-beta-producing NK3 type cells, and NK1 type cells were rare. NK3 type cells in decidua were significantly decreased in miscarriage cases compared with those in normal pregnant subjects. IL-4-, IL-5- or IL-13-producing NK2 type cells were rare in peripheral blood and decidua.These data support the NK1/NK2/NK3/NKr1 hypothesis. NKr1 type cells in peripheral blood and NK3 type cells in decidua might play some important roles in the maintenance of pregnancy by regulation of maternal immune function.

The medical treatment strategies of vitamin D appeared in the guideline of K/DOQI (Kidney Disease Outcomes Quality Initiative) in the U.S. and Clinical algorithms on renal osteodystrophy in Europe. The target intact PTH value is 150-300 pg/mL (16.5-33.0 pmol/L) in U.S. and 9-18 pmol/L (82-164 pg/mL ) in Europe. It was set up more highly in U.S. than in Europe. A European and American medical treatment strategies are not so different from that of Japan in the routes and metabolites of vitamin Ds.

When adenovirus causes haemorrhagic cystitis in immunocompromised patients, vidarabine is used for its treatment because therapeutic choice is limited. Although vidarabine has been reported to be effective for these patients, its therapeutic basis has not yet been established. Vidarabine dose-dependently inhibited viral replication as assessed by a yield reduction assay. Viral protein synthesis was dose-dependently inhibited by vidarabine but not at all by acyclovir, and the degree of inhibition by vidarabine was different for each of the viral proteins, ranging from 0–40% of the untreated control. These results indicated the specificity and mechanism of action of vidarabine against adenovirus. The concentration of vidarabine and its metabolite in the bladder is suggested to exhibit effective anti-adenoviral activity in suppressing the replication of adenovirus. Thus, our results support vidarabine therapy as a possible candidate for adenovirus-induced haemorrhagic cystitis in immunocompromised patients.

Background. Trends in age-adjusted or age-specific incidence rates of end-stage renal disease (ESRD) have never been examined in Japan, a major ESRD epidemic area. Methods. A nationwide registry has provided the number of ESRD patients commencing maintenance renal replacement therapy for time period from 1983 to 2000. We computed gender- and age-specific incidence rates of ESRD over 2-year periods, in total or by cause. Age-adjusted incidence rates were calculated using the 1985 Model Population of Japan as the standard. Results. Causes of ESRD in 1999–2000 were, in order of decreasing frequency, diabetic nephropathy, chronic glomerulonephritis, unknown causes, nephrosclerosis and polycystic kidney disease in men, and chronic glomerulonephritis, diabetic nephropathy, unknown causes, nephrosclerosis and polycystic kidney disease in women. The age-adjusted all-cause incidence of ESRD increased until 1995–1996, but has since levelled off in both genders. The age-adjusted rate for diabetic nephropathy has been rapidly increasing, while that for chronic glomerulonephritis has decreased since 1995–1996. The former rate exceeded the latter in 1997–1998 in men. All-cause ESRD has rapidly increased in the eighties age group, whereas the increase slowed down in younger age groups in the late 1990s. The rate for diabetic nephropathy has linearly risen in almost every age group in men, whereas it began to level off in women aged 40–59 years at about 1995. For chronic glomerulonephritis, the rate had already started to decline in the mid-1980s in those aged

Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.

Objective Intraluminal thrombosis of the catheter was thought to be a major cause of catheter dysfunction. We evaluated if thrombi appear in the luminal side or outside of the catheters placed in the femoral vein in 21 hemodialysis patients. Methods 23 double-lumen catheter (25 cm long and 4 mm diameter polyurethane) strippings were consecutively performed. Mean catheter dwell time was 17.9 +/- 11.2 days (2-45 days). The femoral vein was observed with ultrasound echography, and thrombo-venous ratio (thrombus diameter/vein diameter) was calculated. X-rays were also taken to clearly visualize the thrombi followed by contrast medium injection through the catheter. Results Tube-shaped thrombi were echographically detected in 22 of 23 catheters (95.7%) when the catheter was stripped. Ten catheters (43.5%) were stripped due to the reduced blood flow, and tube-shaped thrombi were observed in the femoral vein, whereas no thrombus was found in the intraluminal side of the catheter. In 7 of 23 patients (30.4%) with leg edema on the same side of the catheter, the thrombovenous ratio was 78.9 +/- 7.4%, which was higher than that in the patients without leg edema (52.1 +/- 11.1%). Conclusion The tube-shaped thrombi, formed around the double-lumen catheter, may cause catheter dysfunction and reduced venous return of the lower legs. The catheter should be removed as soon as thrombosis is diagnosed, especially when accompanied by leg edema.

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 ± 0.2 ng/ml) as compared with controls (1.5 ± 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 ± 0.2 ng/ml vs. polysulfone 3.8 ± 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca × P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.

Adhesion of lymphocytes to glomerular endothelial cells might be a critical step in the development of acute and chronic glomerulonephritis. The protective effect of anti-CD11a and anti-intercellular adhesion molecule (ICAM-1) antibodies on the cytotoxity elicited by phorbol 12-myristate 13-acetate (PMA)-stimulated lymphocytes was investigated by using cultured bovine glomerular endothelial cells (GEN). Both anti-CD11a and CD18 antibodies inhibited GEN injury induced by the activated lymphocytes in a dose-dependent manner. In addition, both antibodies also inhibited the adhesion of the activated lymphocytes to the GEN monolayers. These results suggest that it is important for activated lymphocytes to bind to GEN via adhesion molecules for cytotoxity to be produced by the activated lymphocytes.