Tenascin-C (TN-C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN-C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN-C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN-C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN-C. The immunostaining was semi-quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN-C levels were analysed. Expression of TN-C was specifically detected in endomyocardial biopsy specimens from patients with active-stage inflammation, and disappeared in healed stages. The degree of expression of TN-C correlated with the severity of histological lesions. These data suggest that TN-C reflects disease activity in cases of human myocarditis. Immunostaining for TN-C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens.

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was <500/mm(3) in four patients, >500/mm(3) but <1,000/mm(3) in three patients, and > or =1,000/mm(3) in one patient. In three of the four patients with an initial eosinophil count of <500/mm(3), an increase to > or =500/mm(3) occurred 7-12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

Aim:To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption, we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis, lipid and glucose metabolism, and markers of obesity and inflammation. Methods: A total of 120 patients with dyslipidemia (46 men; mean age 66.5 years), who had not achieved the low density lipoprotein cholesterol (LDL-C) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy, were enrolled and additionally treated with ezetimibe (10 mg/day) for 12 weeks. . Recent studies have elucidated the molecular mechanisms underlying intestinal cholesterol absorption, another potential therapeutic target for hypercholesterolemia. In 2000, Niemann-Pick C1 like 1 (NPC1L1), a transporter protein important for intestinal cholesterol absorption, was cloned. NPC1L1 is composed of 1,359 amino acids, possesses 13 transmembrane spanning IntroductionElevated low density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular diseases and its two sources, i.e., de novo synthesis in the liver and the absorption of dietary and bilialy cholesterol in the intestine, have offered important targets for the treatment of hypercholesterolemia. HMGCoA reductase inhibitors (statins), which target choAddress for correspondence: Shinya Hiramitsu, Fujita Ezetimibe STudy Assembly (FESTA) investigators group, Shiroshita-cho 2-35, Minami-ku, Nagoya 457-0047, Japan E-mail: hirazy@fujita-hu.ac. , together with a growing body of evidence that relates cholesterol absorption to the risk of cardiovascular events 4,5) , has made investigators more aware of the importance of controlling cholesterol absorption for the prevention of these cardiovascular events. Some investigators have reported increased intestinal cholesterol absorption in US and/or European individuals with a history of coronary artery disease 6) , obesity 7) , or type 2 diabetes mellitus 8) , although the relevance of this alteration to these and other pathologies remains to be determined.Based on these considerations, we evaluated the clinical benefit of ezetimibe and its effect on surrogate markers of cholesterol absorption and synthesis in Japanese patients with hypercholesterolemia in order to establish more efficient lipid-lowering therapy. MaterialsBetween June and December 2007, patients who presented to the outpatient clinic of Fujita Ezetimibe Study Assembly were enrolled if they had not achieved the LDL-C goal levels recommended in the 2007 Guideline of the Japan Atherosclerosis Society (JAS) 9) despite diet and exercise without anti-dyslipidemic agents for at least 4 weeks (ezetimibe monotherapy group) or had not achieved the LDL-C management goal levels despite at least 4 weeks of statin therapy (co-administration with ezetimibe and any statin). The study protocol was approved by the Fujita Health University Ethics Committee and all patients gave written informed consent. MethodsAt enrollment, all patients were examined ...

Background A fulminant course can be difficult to predict at the onset of acute myocarditis, so the aim of the present study was to identify the predictive clinical symptoms/signs or laboratory findings. Methods and Results Thirty-nine patients with acute lymphocytic myocarditis, excluding 8 who manifested shock at admission, were studied. The fulminant group was defined as 12 patients who developed shock after admission, requiring intraaortic balloon pumping or percutaneous cardiopulmonary support, and the non-fulminant group comprised the 27 patients without shock. Various parameters at admission were compared between the 2 groups, together with multiple logistic regression analysis, excluding 6 patients with partially missing values. In the fulminant group, C-reactive protein (7.0±7.0 vs 2.3±2.2 mg/dl, p<0.01) and creatine kinase (1,147±876 vs 594±568 IU/L, p<0.05) concentrations were higher, intraventricular conduction disturbances were more frequent (9/12 vs 7/27 patients, p<0.01) and the left ventricular ejection fraction was lower (40.7±13.9 vs 50.1±10.6%, p<0.05) than in the non-fulminant group. In the multiple logistic regression analysis model with the presence/absence of a fulminant course considered as the independent variable, and C-reactive protein, creatine kinase, intraventricular conduction disturbances, and left ventricular ejection fraction as dependent variables, a high-risk group (expected proportion of fulminant course ≥0.5) and a low-risk group (<0.5) could be differentiated. A fulminant course occurred in 9/13 (69%) patients in the high-risk group, but in only 2/20 (10%) patients in the low risk group (p<0.001). Conclusions The risk of a fulminant course of acute myocarditis was high in patients with elevated C-reactive protein, and creatine kinase concentrations, decreased left ventricular ejection fraction, and intraventricular conduction disturbances at the time of admission. (Circ J 2004; 68: 734 -739)

ransient thickening of the ventricular wall sometimes develops in patients with acute myocarditis, 1-17 and we have shown that it is the result of interstitial edema. 1 However, the influence of the ventricular wall thickening per se on left ventricular function in acute myocarditis has not been elucidated, so we reviewed serial echocardiograms of patients with acute myocarditis and attempted to determine the relationship between ventricular wall thickening and left ventricular function. Methods Study PatientsDuring the 12-year period from 1987 to 1998, 60 patients at Fujita Health University Hospital or Nagoya Dai-ni Red Cross Hospital were diagnosed as having acute myocarditis based on clinical symptoms and endomyocardial biopsy findings. Echocardiography and right ventricular endomyocardial biopsies were performed during both the acute (≤2 weeks after onset) and convalescent (≥1 month after onset) phases in 29 of the patients. Of these, 9 patients with second or third degree atrioventricular block were excluded, and the remaining 20 patients comprised the current study group (12 men, 8 women; mean age, 36.5±16.1 years) ( Table 1). In addition to the conventional pharmacological therapies, steroids, catecholamines, and diuretics were being taken by 5, 13, and 16 patients, respectively. Percutaneous cardiopulmonary support and intraaortic balloon pumping were used in 2 patients each. Endomyocardial BiopsiesRight ventricular endomyocardial biopsies were performed, and at least 3 tissue fragments were obtained in each patient. The samples were fixed immediately in 10% buffered formalin, and multiple sections were stained with hematoxylin-eosin, Azan-Mallory, and elastica van Gieson stains for light microscopic examination. The histologic sections were analyzed by 3 observers, and a diagnosis of myocarditis was reached by consensus. The final diagnosis of lymphocytic myocarditis [18][19][20] was based on the Dallas criteria. 18 Only patients with histologic evidence of "active" myocarditis were included.Eosinophilic myocarditis [21][22][23][24] was defined as the development of cardiac symptoms in the presence of peripheral blood eosinophilia and endomyocardial biopsy evidence of eosinophilic infiltration, degranulation, and myocyte necrosis. Using the Azan-Mallory-stained specimens, myocardial