Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.     

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

Background

Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.

Methods

IMN patients with SRNS (age 16–75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2–3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.

Results

Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3–1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.

Conclusion

CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2–3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.     

Simultaneous measurement of TSH-binding inhibitor immunoglobulin and thyroid stimulating autoantibody activities using cultured FRTL-5 cells in patients with untreated Graves' disease

A new and practical assay was developed using cultured FRTL-5 cells for simultaneous assessment of TS-ab and TSH-binding inhibitor immunoglobulin, allowing direct comparison of these two activities under the same conditions. Subsequent to the TS-ab assay in which extracellular cAMP concentration in Hanks' medium without NaCl was determined, [125I]b TSH in this medium was added to observe the ability of serum Ig to inhibit the binding of [125I]b TSH to FRTL-5 cells. We found a much higher specific binding of [125I]b TSH to FRTL-5 cells and a much greater inhibition of [125I]bTSH binding to the cells exposed to Graves' Ig in hypotonic NaCl-free than in NaCl containing Hanks' medium, indicating that the binding of both TSH and Graves' Ig to the TSH receptor was salt-sensitive. The inhibitory activity of [125I]bTSH binding to the cells was 0.2 +/- 4.6% (mean +/- SD) in 45 normals. Inter-assay coefficients of variation in two positive controls with the mean values of 18.0 and 65.8% were 15.8 and 16.5%, respectively. Among 46 patients with untreated hyperthyroidism owing to Graves' disease, 45 (97.8%) were positive for TS-ab; 35 (76.1%) and 40 (87.0%) were positive for TSH-binding inhibitor in Ig assays using FRTL-5 cells and solubilized porcine thyroid membranes, respectively. TS-ab activities correlated less closely with TSH-binding inhibitory activities determined using FRTL-5 cells (r = 0.576, p less than 0.001) than with those determined using porcine thyroid membranes (r = 0.745, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig

Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.     

Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study.

BACKGROUND: The present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness, as assessed with pulse wave velocity (PWV), in patients with coronary artery disease (CAD) and hyperlipidemia over the long term. METHODS AND RESULTS: Ninety-three patients were randomly assigned to either fluvastatin (group A, n=50) or bezafibrate (group B, n=43) and followed for 5 years. There was no difference in the clinical findings between the 2 groups. In group A, there was a progressive reduction in the brachial-ankle PWV along with a decrease in serum low-density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) by 12 months after fluvastatin, and the improvement was maintained until 5 years after treatment. In group B, despite identical lowering of the serum lipid, PWV was progressively increased. In group A, the percentage change in PWV correlated significantly with that of the serum CRP (r=0.49, p<0.001), but not with that of the serum LDL-C after treatment. CONCLUSIONS: The beneficial vascular effects of fluvastatin persisted for a long period in patients with CAD and hyperlipidemia. Its anti-inflammatory action might contribute to the favorable effects on arterial stiffness.     

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu–Yamaguchi Children’s Cancer Study Group

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.     

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

Effects of the Implant Design on Peri‐Implant Bone Stress and Abutment Micromovement: Three‐Dimensional Finite Element Analysis of Original Computer‐Aided Design Models

Background: Occlusal overloading causes peri‐implant bone resorption. Previous studies examined stress distribution in alveolar bone around commercial implants using three‐dimensional (3D) finite element analysis. However, the commercial implants contained some different designs. The purpose of this study is to reveal the effect of the target design on peri‐implant bone stress and abutment micromovement. Methods: Six 3D implant models were created for different implant–abutment joints: 1) internal joint model (IM); 2) external joint model (EM); 3) straight abutment (SA) shape; 4) tapered abutment (TA) shapes; 5) platform switching (PS) in the IM; and 6) modified TA neck design (reverse conical neck [RN]). A static load of 100 N was applied to the basal ridge surface of the abutment at a 45‐degree oblique angle to the long axis of the implant. Both stress distribution in peri‐implant bone and abutment micromovement in the SA and TA models were analyzed. Results: Compressive stress concentrated on labial cortical bone and tensile stress on the palatal side in the EM and on the labial side in the IM. There was no difference in maximum principal stress distribution for SA and TA models. Tensile stress concentration was not apparent on labial cortical bone in the PS model (versus IM). Maximum principal stress concentrated more on peri‐implant bone in the RN than in the TA model. The TA model exhibited less abutment micromovement than the SA model. Conclusion: This study reveals the effects of the design of specific components on peri‐implant bone stress and abutment displacement after implant‐supported single restoration in the anterior maxilla.