Feasibility of diagnosing chronic myocarditis by endomyocardial biopsy

Summary In studies of all the layers of autopsied hearts from patients with chronic myocarditis, local clusters of lymphocytes are frequently noted, in contrast with hearts obtained from patients with acute myocarditis. Myocardial biopsy specimens, however are no larger than about 2mm×3mm. With this in mind, the present study was undertaken to determine whether chronic myocarditis can be diagnosed by endomyocardial biopsy. Specimens were obtained from seven patients in whom chronic myocarditis was confirmed by the clinical course and by autopsy findings. In H&E stained specimens, sites corresponding to the biopsy sites in both ventricles (right ventricular free wall, right ventricular side of the ventricular septum, left ventricular lateral wall) were selected at random (five sites each from the right and left ventricles in each patient) and examined under a light microscope. A mean of 5 or more lymphocytes per visual field (by light microscopy at 400-fold magnification), a proposed quantitative diagnostic criterion of myocarditis, was noted in the right ventricle in three patients (5 lymphocytes in two patients and 6 in one patient) and in the left ventricle in one patient (5 lymphocytes). Also, when the presence of lymphocyte clusters, considered to be a characteristic feature of chronic myocarditis, was determined, clusters of 20 or more lymphocytes per visual field were found in the same patients as those mentioned above, namely, in three patients (42.8%) in the right ventricle, as mentioned above, and in one patient (14.3%) in the left venricle. At the sites of these lymphocyte clusters, findings such as degenerative changes of the myocardial cells and interstitial fibrosis were also associated, making possible a diagnosis of myocarditis. Therefore, in chronic myocarditis, even if five specimens are obtained by right ventricular biopsy, in approximately one half of patients the diagnosis of chronic myocarditis will be missed because of sampling errors.     

Cardiac Biopsy Conference in Japan, November 30 to December 1, 2007

A 21-week-embryonic age girl. Mother has previous history of an artificial termination of 1st. fetus at 18-weeks-gestational age after prenatal diagnosis for Potter’s syndrome (type II). She was admitted because of suspected presence of cardiovascular anomaly in fetus at 20-weeks-gestational age and underwent an artificial termination after prenatal diagnosis of truncus arteriosus, polycystic kidney, single umbilical artery and cystic hygroma without chromosomal abnormalities for 13, 18 and 21 trisomy. Autopsy confirmed the presence of posterior-set ears, underdeveloped jaws, absence of thymus, right polycystic kidney, single umbilical artery, cystic hygroma, pulmonary atresia with ventricular septal defect (tetralogy-atresia), major aorto-pulmonary collateral artery and right aortic arch, being strongly suggestive of DiGeorge syndrome. Chromosomal abnormality for 22q11.2 deletion was identified from blood sample of mother with facial abnormality. It has been reported that patients with the chromosome 22q11.2 deletion syndrome (DiGeorge syndrome) have both tetralogy of Fallot (15.3%) and truncus arteriosus (34.5%). Furthermore, we recognized abnormal conal septum and subpulmonary conal free wall in this case, as with truncus arteriosus. Therefore, it was suggestive for abnormality of common pathway in proper cardiac morphogenesis between tetralogyatresia and truncus arteriosus.     

Simultaneous Administration of 2-Aminoethyl Diphenylborinate and Chloroquine Reverses Chloroquine Resistance in Malaria Parasites

A nearly complete reversal of chloroquine (CQ) resistance in the CQ-resistant Plasmodium falciparum K-1 strain, with a significant decrease in the mean ± standard deviation (SD) 50% inhibitory concentration (IC₅₀) from 1,050 ± 95 nM to 14 ± 2 nM, was achieved in vitro by the simultaneous administration of 2-aminoethyl diphenylborinate (2-APB). The CQ resistance-reversing activity of 2-APB, which showed the same efficacy as verapamil, was also observed in an in vivo mouse infection model with the CQ-resistant Plasmodium chabaudi AS(30CQ) strain.     

Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation

AIM: To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS: The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.RESULTS: Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.CONCLUSION: To detect PBM without biliary dilatation before onset of gallbladder cancer, we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.     

Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats

Angiotensin II (Ang II) is a potent stimulator of plasminogen activator inhibitor-1 (PAI-1) expression, which is an important regulator of pathogenesis of atherosclerosis. Rho-kinase, a downstream target protein of small GTP-binding protein Rho, plays a key role for various cellular functions. We evaluated the cardioprotective effects of a specific Rho-kinase inhibitor, (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), and an Ang II type 1 receptor antagonist, candesartan, on PAI-1 gene expression and cardiovascular remodeling in Ang II-induced hypertensive rats. Rats given Ang II alone (200 ng.kg(-1).min(-1)) were compared with rats also receiving Ang II plus Y-27632 or Ang II plus candesartan. Ang II-induced PAI-1 mRNA up-regulation in the left ventricle was inhibited by Y-27632 and candesartan. In addition, increased RhoA protein, Rho-kinase, and c-fos gene expression, and myosin light chain phosphorylation were suppressed by Y-27632 and candesartan. In contrast, Y-27632 had no effect on Ang II-stimulated phospho-p42/p44 extracellular signal-regulated kinases (ERK) and phospho-p70S6 kinase activities, which are reported to be involved in Ang II-induced protein synthesis. Moreover, activated Ang II-induced phosphorylation of ERK and p70S6 kinase were blocked by candesartan. Y-27632 or candesartan administration resulted in significant improvements in the wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These results suggested that differential activation of Rho-kinase and ERK pathways may play a critical role in Ang II-induce PAI-1 gene expression, and up-regulation of Rho-kinase plays a key role in the pathogenesis of Ang II-induced hypertensive rats. Thus, inhibition of the Rho-kinase pathway may be at least a useful therapeutic strategy for treating cardiovascular remodeling.     

Significance of changes in plasma adiponectin concentration after the implantation of stents in patients with stable angina

OBJECTIVE: Although plasma adiponectin levels may be a marker for the severity of coronary artery disease (CAD) and can help to predict future cardiovascular events in patients with CAD, the significance of changes in plasma adiponectin levels after the implantation of stents in patients with stable angina is unclear. METHODS: The subjects included 32 consecutive patients with stable angina who had undergone successful coronary stenting [bare metal stent (BMS, n=16) or sirolimus-eluting stent (SES, n=16)]. Blood sampling was performed at baseline, and at 24h, 48h, 14 days and 6 months after stenting. RESULTS: Plasma high-sensitivity C-reactive protein (hs-CRP) levels at baseline (0.16+/-0.15mg/dl) were significantly increased at 24h (0.36+/-0.45mg/dl, p=0.011) and 48h (1.01+/-1.01mg/dl, p<0.001), and plasma adiponectin levels at baseline (6.7+/-4.2mug/ml) were significantly decreased at 24h (6.1+/-4.2mug/ml, p=0.019) and 48h (6.2+/-4.9mug/ml, p=0.010) in all subjects. Although there were no significant differences in changes in plasma hs-CRP and adiponectin levels between BMS and SES groups during the study period, BMS group (6.5+/-0.9mug/ml at baseline) showed a significant reduction of plasma adiponectin at 48h (5.8+/-1.1mug/ml, p=0.022) and 6 months after stenting (4.7+/-2.3mug/ml, p=0.011). Percent diameter stenosis (%DS) at 6 months after stenting was negatively correlated with changes in the plasma adiponectin levels within 6 months [Deltaadiponectin (6 months-baseline)]. In addition, multiple logistic regression analysis revealed that the %DS at 6 months after stenting was most closely correlated with Deltaadiponectin (6 months-baseline) after adjusting for age, sex and body mass index. CONCLUSIONS: Coronary stenting may decrease circulating adiponectin in association with an inflammatory response. The changes in plasma levels of adiponectin after stenting may also be a predictor of coronary restenosis in patients with CAD.     

过敏性紫癜的中医病因病机与治疗

过敏性紫癜是一种过敏性毛细血管和细小血管的血管炎,引起血液和血浆外渗至皮下、黏膜下和浆膜下而出现皮肤或黏膜损害。本病好发于下肢,临床上以皮肤或黏膜发生紫红色瘀点,伴关节疼痛、腹部症状及肾脏损害为特征。中医称过敏性紫癜为葡萄疫,其病因病机为风湿热毒邪气袭表、饮食所伤、肝肾阴虚及气不摄血。针对其病因病机及临证将其分为风热伤络型、血热妄行型、湿热痹阻型、肝肾阴虚型、气不摄血五种证型进行中医辨证论治。此外亦包括针灸治疗及外治法。