Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy

Background: Iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by ¹²³I-MIBG cardiac scintigraphy, whereas abnormal ¹²³I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. Hypothesis: Based on evidence from recent studies, it can be hypothesized that ¹²³I-MIBG uptake is related to histopathologic changes in the myocardium. Methods: The relation of ¹²³I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The ¹²³I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The ¹²³I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. Results: All of the global, mean, and biopsy region scores for ¹²³I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the ¹²³I-MIBG uptake scores. Conclusion: These results indicate that ¹²³I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.     

Pharmacokinetics of 4′-cyano-2′-deoxyguanosine,a novel nucleoside analog inhibitor of the resistant hepatitis B virus,in a rat model of chronic kidney disease

IntroductionThe novel nucleoside analog, 4′-cyano-2′-deoxyguanosine (CdG), possesses inhibitory activity against both the wild-type and resistant hepatitis B virus. Since the dosage of the currently available nucleoside analog preparations needs to be adjusted, depending on renal function, we investigated the effect of renal dysfunction on the pharmacokinetics of CdG in a rat model of chronic kidney disease (CKD).MethodsCKD model rats were either intravenously or orally administered CdG at a dose of 1 mg/kg. The concentration of CdG in plasma, organs (liver and kidney) and urine samples were determined by means of a UPLC system interfaced with a TOF-MS system.ResultsFollowing intravenous administration, the plasma retention of CdG was prolonged in CKD model rats compared to healthy rats. In addition, the clearance of CdG was well correlated with plasma creatinine levels in CKD model rats. Similar to the results for intravenous administration, the plasma concentration profiles of CdG after oral administration were also found to be much higher in CKD model rats than in healthy rats. However, the results for the organ distribution and urinary excretion of CdG, the profiles of which were similar to that of healthy rats, indicated that CdG did not accumulate to a significant extent in the body.ConclusionThe extent of renal dysfunction has a direct influence on the pharmacokinetics (plasma retention) of CdG without a significant accumulation, indicating that the dosage of CdG will be dependent on the extent of renal function. .     

Fatal eosinophilic heart disease in a child with neurofibromatosis-1 complicated by acute lymphoblastic leukemia

We present a pediatric case of neurofibromatosis-1 (NF-1) complicated by acute lymphoblastic leukemia and hypereosinophilia, which caused multiple end-organ damage. Although clinical symptoms such as fever and coughing were noted only 1 week before admission, the condition deteriorated rapidly with a fatal outcome prior to antileukemic therapy. A postmortem examination demonstrated extensive endomyocardial fibrosis with thrombotic occlusion and recanalization of the coronary arteries. Leukemic cell infiltration was not seen in the cardiac tissue. When eosinophilia is diagnosed in patients with NF-1, eosinophilic end-organ damage, particularly cardiac involvement, in addition to hematological malignancies, should be screened for in order to start medical treatment at the early stage of the disease.     

Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice.

BACKGROUND: Angiotensin II (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT1) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT1 receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes. METHOD AND RESULTS: Hearts from MLP knockout (MLPKO) mice and MLP-AT1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts. CONCLUSIONS: The AT1a receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy.     

Serum amyloid A and C‐reactive protein positive nodule in alcoholic liver cirrhosis,hard to make definite diagnosis

We describe a case of serum amyloid A (SAA) and C‐reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37‐year‐old woman with alcohol‐related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography‐guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non‐nodular portion. gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid‐binding protein and glutamine synthetase, but negative for β‐catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non‐nodular portion of the alcohol‐related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol‐related liver cirrhosis than by malignant transformation into HCC.