Myocardial damage by resuscitation methods

Medico-legal autopsy cases were reviewed to detect myocardial changes induced by resuscitation methods. Myofibrillar degeneration (MFD) induced by resuscitation methods was classified into two types according to Luxol fast blue staining: contraction band (CB) and diffuse staining (DS). In the cases in which cardiopulmonary resuscitation had been performed, myocytes showing CB or DS formed small foci and were distributed in the papillary muscles, septum, and inner to middle layers of the myocardium. MFD induced by vasopressors was characterized by solitary distribution of degenerating myocytes that mainly showed DS and sometimes CB. When direct current countershocks had been performed, focal MFD in the subepicardial zone appeared to be a characteristic feature.     

Diffusion abnormalities of the uncinate fasciculus in Alzheimer’s disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract

Introduction Our aim was to determine diffusion abnormalities in the uncinate fasciculus (UF) in Alzheimer’s disease (AD) by diffusion tensor tractography (DTT) using a new method for measuring the core of the tract. Methods We studied 19 patients with AD and 19 age-matched control subjects who underwent MRI using diffusion tensor imaging (DTI). DTT of the UF was generated. The mean diffusivity (MD) and fractional anisotropy (FA) of the core of the tract were measured after voxelized tract shape processing. Student’s t-test was used to compare results between patients with AD and controls. Intraobserver correlation tests were also performed. Results FA was significantly lower (P < 0.0001) in the UF of patients with AD than of controls. There was no significant difference in MD along the UF between the two groups. Intraobserver reliability (intraclass correlation coefficient) for the first and second measurement was r > 0.93 for measured FA and r > 0.92 for measured MD. Conclusion Our results suggest that FA reflects progression of AD-related histopathological changes in the UF of the white matter and may represent a useful biological index in monitoring AD. Diffusion tensor tract-specific analysis with voxelized tract shape processing to measure the core of the tract may be a sensitive tool for evaluation of diffusion abnormalities of white matter tracts in AD.     

Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer’s disease: tract-specific analysis

Purpose

The aim of this study was to determine diffusion abnormalities in the posterior cingulate fiber tracts (PCFTs) in patients with Alzheimer’s disease (AD) by diffusion tensor tractography (DTT).

Materials and methods

We studied 23 AD patients and 18 age-matched normal controls who underwent magnetic resonance imaging using diffusion tensor imaging (DTI). DTT of PCFTs was generated from DTI. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in co-registered voxels along with DTT of PCFTs. Student’s t-test was used to compare results between the AD patients and normal controls.

Results

The MD in PCFTs was significantly higher in AD patients than in normal controls (P = 0.019). The FA in PCFTs was significantly lower in AD patients than in normal controls (P = 0.007).

Conclusion

The abnormal MD increase and FA decrease, which is considered to indicate a net loss of barriers that restrict water molecular motion and tissue anisotropy of white matter, is consistent with neuropathological data that demonstrate partial loss of myelin, axons, and oligodendrial cells in white matter of AD brains. Our results suggest that MD and FA reflect progression of AD-related histopathological changes in the PCFTs and may represent a useful biological index for monitoring AD.     

Aspirin attenuates the incidence of silent brain lesions in patients with nonvalvular atrial fibrillation.

BACKGROUND: Abnormal findings, including silent cerebral infarction, are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF); however, the prevalence and prevention strategy for these lesions have not been extensively studied. In the present study the preventive effects of aspirin on silent ischemic lesions was investigated. METHODS AND RESULTS: Silent lesions were counted using cranial MRI performed in 78 neurologically normal adults with sinus rhythm and in 212 patients with NVAF without a history of stroke. MRIs were repeated twice in the NVAF patients at 12-month intervals. During the first year, patients received neither antiplatelet agent nor anticoagulant; in the second year, aspirin (330 mg daily) was administered. The prevalence of lesions in the initial MRI was higher in NVAF patients (86.4%) than in sinus rhythm subjects (53.8%; p<0.001). After 12 months without aspirin, new lesions were seen in 20.6% of NVAF patients. The yearly occurrence of new lesions was decreased to 9.6% during the year of treatment with aspirin (p=0.014). CONCLUSIONS: In patients with NVAF, abnormal lesions are frequently observed by MRI and aspirin treatment may be effective in preventing further small silent lesions.     

Neurological improvement and prognosis after occipito-thoracic fusion in patients with mutilating-type rheumatoid arthritis

Introduction

Mutilating-type rheumatoid arthritis, the most aggressive type of rheumatoid arthritis, is frequently associated with destructive cervical involvement, both at the high-cervical and subaxial levels, causing significant neurological deficit, and their natural course of the disease and the survival are discouraging. For such cases, we have been actively performing occipito-thoracic fusion since 1991. Although medical treatment for rheumatoid patients has represented a marked improvement, it could not treat all of these patients because of several reasons. Therefore, it is still important to evaluate the past treatment results.

Methods

We investigated the neurological improvement and prognosis in 51 mutilating-type rheumatoid arthritis patients who underwent occipito-thoracic fusion between 1991 and 2010. The neurological status was evaluated using modified Ranawat classification; class IIIB was subdivided into IIIBa (able to sit upright) and IIIBb (bedridden).

Results

The preoperative neurologic status was IIIBa in 19 patients and IIIBb in 17 patients. 15 of the 19 patients with class IIIBa improved to being able to walk (79 %), whereas only 3 of the 17 patients with class IIIBb improved to being able to walk (18 %) after surgery. Of the 51 patients, 28 died during follow-up; the mean age at death was 67.2 years. The postoperative 5- and 10-year survival rates were 60.3 and 26.4 %, respectively.

Conclusion

The neurological improvement and prognosis after surgery was poorer in class IIIBb patients than in the other patient groups. Occipito-thoracic fusion can improve the neurological symptoms and prognosis. However, early surgical intervention is recommended, before a patient becomes bedridden (class IIIBb).     

Reduced production of polymeric immunoglobulin receptor in murine dextran sodium sulfate-induced colitis

Polymeric immunoglobulin receptor (pIgR) plays an intrinsic role in protecting the intestinal tract from invading pathogens. In the present study, we observed a decrease in pIgR in colon lysate from mice with dextran sodium sulfate (DSS) colitis. A decrease in pIgR was detected in both mRNA and protein levels. Histologic examinations revealed marked destruction of intestinal epithelial cells (IECs), and only a small number of regenerating IECs expressed pIgR. These results suggest that the decrease in pIgR was due to the destruction of IECs. Because activation of toll-like receptor 3 slows the progression of DSS colitis, we injected polyriboinosinic: polyribocytidylic acid (poly I:C) intraperitoneally and observed the correlation between pIgR level and severity of DSS colitis. Poly I:C markedly decreased progression of DSS colitis, and pIgR levels significantly recovered. Furthermore, we found that expressions of IFN-γ and TNF-α were higher in DSS colitis. These results indicate that the decrease in pIgR was not compensated for by increased expression of these cytokines. In sum, our findings show that pIgR levels vary according to the severity of DSS colitis and that these changes might be useful as a biomarker of the severity of inflammatory bowel disease.     

Andersen-tawil syndrome associated with aborted sudden cardiac death: atrial pacing was effective for ventricular arrhythmias

ABSTRACT:: A 37-year-old Japanese woman experienced aborted sudden cardiac death from ventricular fibrillation and was diagnosed with Andersen-Tawil syndrome by genetic analysis that revealed 2 mutations in the KCNJ2 gene. Although she received an implantation of implantable cardioverter defibrillator and beta-blocker therapy, the frequency of premature ventricular contraction and bidirectional ventricular tachycardia did not decrease. Her ventricular arrhythmias increased after a full stomach test and a neostigmine provocation test, and reduced after cibenzoline administration, which indicates the relation with vagal tone. Moreover, increasing the pacing rate significantly decreased them. These findings indicate that the arrhythmia was bradycardia-dependent in this case.     

High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype

Background

The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy.

Methods

A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes.

Results

The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone.

Conclusions

Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.