Fulminant type 1 diabetes mellitus with anti‐programmed cell death‐1 therapy

Anti‐programmed cell death‐1 (PD‐1) antibodies are regarded as a risk factor for insulin‐dependent diabetes mellitus as a side‐effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin‐dependent diabetes during anti‐PD‐1 therapy. A 55‐year‐old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C‐peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti‐PD‐1 therapy can cause rapid onset of insulin‐dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti‐PD‐1 therapy.     

The Association of Cardio-Ankle Vascular Index (CAVI) with Biatrial Remodeling in Atrial Fibrillation

Aim: Arterial stiffness results in elevated left ventricular filling pressure and can promote atrial remodeling due to chronic pressure overload. However, the impact of arterial stiffness on the process of atrial remodeling in association with atrial fibrillation (AF) has not been fully evaluated. Methods: We enrolled 237 consecutive patients diagnosed with AF who had undergone ablation; data from 213 patients were analyzed. Cardio-ankle vascular index (CAVI) was used as a marker of arterial stiffness. The left atrial (LA) and right atrial (RA) volumes were determined by computed tomography imaging; atrial conduction and voltage amplitude were evaluated using a three-dimensional electromapping system used to guide the ablation procedure. Result: In univariate analysis, CAVI significantly correlated with atrial structural and electrical remodeling (LA volume index, r =0.297, P =0.001; RA volume index, r =0.252, P =0.004; LA conduction velocity, r =0.254, P = 0.003; LA mean voltage, r =−0.343, P =0.001, RA mean voltage; r =−0.245, P =0.015). Multivariate regression analysis revealed that CAVI and plasma levels of N-terminal B-type natriuretic peptide were independent determinants of LA and RA remodeling, respectively. On the other hand, age and LA conduction velocity were independent variables with respect to CAVI. Age-adjusted CAVI was highest in long-standing persistent AF when compared with measures of persistent or paroxysmal AF. Conclusion: CAVI was closely associated with biatrial remodeling in patients diagnosed with AF. These results suggest that arterial stiffness may play a significant role with respect to disease progression.     

Primary varicella infection in children with systemic juvenile idiopathic arthritis under tocilizumab therapy

Abstract

We report the clinical course and outcome of primary varicella infection in six children with systemic juvenile idiopathic arthritis (sJIA) receiving tocilizumab. None had disseminated or fatal varicella infection, but one patient developed macrophage activation syndrome (MAS) and another had an arthritis relapse. All patients had a significant elevation of serum IL-6 levels, and the two children who developed MAS or arthritis relapse showed high serum IL-18 levels, which could cause a sJIA flare-up.     

Community control studies on Strongyloides infection in a model island of Okinawa, Japan

The community control program for Strongyloides infection was conducted by fecal examination and subsequent treatment of the population on a model island (Kume Island) in Okinawa, Japan, for 5 years from 1993 to 1997. More than 1,200 persons, accounting for 17% to 20% of the persons subjected, received fecal examinations each year. The positive rate in 1993 was found to be 9.7% (133/1,374). The positive rate decreased to 6.5% (95/1,468) in 1994, then 4.8% (60/1,245) in 1995, 2.2% (27/1,225) in 1996 and 2.7% (33/1,217) in 1997 through treatment with albendazole or ivermectin on the positive persons detected each year. Among the positive persons detected after operation of the control program, more than 70% were newly detected persons who did not receive an examination in the previous year or were falsely-negative in the previous examination. The low enforcement of procuring fecal examinations, as well as low sensitivity of fecal examination, might have had an effect on the relatively gradual decrease in the prevalence rate, in spite of the high efficacy of the treatment. The results indicate that continuation of the control program for several years is needed to effectively reduce the prevalence of the parasitic infection in the community.     

Effect of total knee arthroplasty on disease activity in patients with established rheumatoid arthritis: 3-year follow-up results of combined medical therapy and surgical intervention

Though excellent clinical results have been reported for total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients, the medium-term effect of TKA on RA disease activity remains unknown. This analysis aimed to assess changes in disease activity after TKA in patients with established RA. We analyzed the systemic effects of TKA on RA disease activity 3 years after intervention. Routine clinical and laboratory assessments were recorded at baseline, less than less than 0.5 years after TKA, and 3 years after TKA. Of the registered RA patients, 130 TKA patients were followed for 3 years after surgery. RA disease activity was measured using the Disease Activity Score 28 (DAS28). Patients were divided into three groups by preoperative baseline DAS28: low (DAS28 ≤ 3.2, n = 8), moderate (DAS28 > 3.2 but ≤5.1, n = 68), and high (DAS28 > 5.1, n = 54) disease activity. The postoperative DAS28 (<0.5 years [DAS1] and 3 years [DAS3] after surgery) scores of each patient were compared to their baseline (DAS0) scores using the paired t-test. The mean DAS28 decreased from 4.85 (DAS0) to 4.14 (DAS1; P = 1.07E-12), and this decrease was sustained at 3 years (DAS3 = 3.97; P = 4.73E-15). Subanalysis results revealed a systemic effect of TKA on disease activity in patients with moderate or high disease activity (DAS0 = 4.33; DAS1 = 3.72 [P = 5.94E-06]; DAS3 = 3.81 [P = 7.89E-06]; and DAS0 = 5.79; DAS1 = 4.86 [P = 1.14E-08]; DAS3 = 4.37 [P = 1.03E-11], respectively). While no significant changes in medication were noted, the average dose of prednisolone tended to decrease over time. We conclude that TKA, which is known to result in good clinical outcomes for damaged knees, has a secondary systemic effect on RA disease activity. Combination therapy consisting of medical treatment and surgical intervention is thought to effectively improve the condition of RA patients who have destructive arthritis in the knee joint, with the effect lasting for at least 3 years.     

Effect of Low‐Density Lipoprotein Apheresis for Nephrotic Idiopathic Membranous Nephropathy as Initial Induction Therapy

Low‐density lipoprotein apheresis (LDL‐A) has been used for nephrotic syndrome (NS) caused by focal segmental glomerulosclerosis in Japan. Idiopathic membranous nephropathy (iMN) can also cause treatment‐resistant NS. Therefore, we investigated the effect of LDL‐A during initial induction for it. This retrospective, observational, and single‐center study enrolled consecutive iMN patients who received steroids from March 2000 to May 2015. We compared data between 11 patients treated with LDL‐A (LDL‐A group) and 27 patients without (non‐LDL‐A group) at baseline and 4 and 8 weeks later. Reduction rate of proteinuria and increase rate of serum albumin in LDL‐A group were significantly higher than the other after 4 weeks (P = 0.036 and 0.030) and 8 weeks (P = 0.030 and <0.001), respectively. There was no adverse event caused by LDL‐A and immunosuppressant dose was not significantly different. In conclusion, LDL‐A may be an effective choice for initial induction of nephrotic iMN.     

恶性疟原虫11.1基因3个重复片段的克隆及表达

目的　克隆和表达恶性疟原虫 (Pf) 11 1基因产物中的 3个重复片段 3R、6R和 9R。方法　利用设计的引物从培养的恶性疟原虫 3D7株的基因组DNA中扩增出 3个重复片段。PCR产物被克隆入pT7载体中以进双向测序。测序结果用GENETYX MAC软件进行分析。扩增的片段亚克隆入pET32a(+ )或pET32b(+ ) ,并由IPTG诱导在大肠杆菌BL2 1中表达重组蛋白。结果　用PCR方法成功地扩增出 3R、6R和 9R片段 ,大小分别为 5 5 2、630和44 4bp。测序结果显示 ,3D7株的Pf11 1基因比PaloAlto株的Pf11 1基因多 4个 3AA和 1个 6AA重复单元 ,两原虫株的 3R和 6R片段的同源性分别 92 8%和 95 1%。扩增出的 9R片段含有 13个 9AA重复单元。在BL2 1菌株中表达出三个重组蛋白 ,分子量分别为 45、60和 42kDa。结论　用PCR方法分别获得 3R、6R和 9R重复片段并在大肠杆菌中成功表达。 3D7株的Pf11 1基因与PaloAlto株具有高度同源性     

Can Aggressive Lipid Lowering Using Low-Density Lipoprotein Apheresis Prevent Restenosis After Percutaneous Transluminal Coronary Angioplasty in Patients with Normocholesterolemia?

Abstract: We examined whether aggressive lipid lowering using low-density lipoprotein (LDL) apheresis could prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). Fifteen patients with 17 lesions underwent LDL apheresis once within a week before and after PTCA and thereafter every 2 or 3 weeks (apheresis group) for about 4 months. The control group consisted of 17 patients with 17 lesions. No patients received additional lipid lowering drugs after PTCA. In the apheresis group, the time interval means of the total and LDL cholesterol levels were significantly lower than those in the control group whereas no significant differences were found between the 2 groups regarding the mean percent diameter stenosis or minimal lumen diameter before and after PTCA and at follow-up. The restenosis rate was 29.4% in the apheresis group and 47.1% in the control group. The restenosis rate tended to be slightly lower in the apheresis group. The overall results, however, indicated that aggressive lipid lowering does not prevent restenosis.     

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

It has been suggested that proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, may function as a component of the tissue renin-angiotensin system (RAS). To investigate the role of proang-12 in the production of angiotensin II (Ang II), we measured its plasma and tissue concentrations in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, with and without RAS inhibition. The 15-week-old male WKY and SHR rats were left untreated or were treated for 7 days with 30?mg?kg(-1) per day losartan, an angiotensin receptor blocker, or with 20?mg?kg(-1) per day imidapril, an angiotensin-converting enzyme (ACE) inhibitor. Both treatments increased renin activity and the concentrations of angiotensin I (Ang I) and Ang II in the plasma of WKY and SHR rats, but neither affected plasma proang-12 levels. In contrast to the comparatively low level of proang-12 seen in plasma, cardiac and renal levels of proang-12 were higher than those of Ang I and Ang II. In addition, despite activation of the RAS in the systemic circulation, tissue concentrations of proang-12 were significantly reduced following treatment with losartan or imidapril. Similar reductions were also observed in the tissue concentrations of Ang II in both strains, without a reduction in Ang I. These results suggest that tissue concentrations of proang-12 and Ang II are regulated independently of the systemic RAS in WKY and SHR rats, which is consistent with the notion that proang-12 is a component of only the tissue RAS.     

Heparin-released extracellular superoxide dismutase is reduced in patients with coronary artery atherosclerosis

OBJECTIVES: We studied whether the amount of heparin-released extracellular superoxide dismutase (EC-SOD), which is an antioxidative enzyme, is associated with coronary artery disease (CAD). METHODS AND RESULTS: EC-SOD was measured in plasma at basal and at post-heparin injection in 315 patients. Heparin-released EC-SOD was calculated as the difference between the two values. After exclusion of a mutant EC-SOD group (n = 27:8.6%), 288 patients were divided into three groups by angiographic findings; those with normal coronary (the normal group; n = 63), those with atherosclerosis without significant stenosis (the mild atherosclerosis group; n = 36), and those with significant stenosis (the atherosclerosis group; n = 189). Although the basal values were similar among the three groups, heparin-released EC-SOD levels were significantly lower in the atherosclerosis group (131.0 +/- 42.8 ng/ml, p = 0.0003) than in the normal group (156.9 +/- 66.2 ng/ml). Moreover, logistic analysis revealed that heparin-released EC-SOD independently contributed to CAD. The coronary score showed a significant correlation with heparin-released EC-SOD. As for factors affecting the level of heparin-released EC-SOD, the level of high-density lipoprotein cholesterol and age showed a positive correlation. CONCLUSIONS: The results suggest that heparin-released EC-SOD is significantly reduced in CAD and that the tissue-bound location of this enzyme might be important for antioxidative function.