Heart in an eggshell--eggshell appearance calcified constrictive pericarditis demonstrated by three-dimensional images of multislice computed tomography

We describe a patient who presented with highly calcified eggshell-like constrictive pericarditis. Electrocardiogram-gated multislice computed tomography showed the degree and configuration of calcification in the pericardium and could be used to evaluate cardiac motion restrictions by calcified pericardium visually in 4D. The results described show a novel condition, a cardiac constriction by extensive calcification of the pericardium, and compression of the inferior wall of the LV due to a mass, thought to be a hematoma, located inside the pericardium.     

Appearance of noncompaction-like remodeling of the anatomical right ventricle in a middle-aged subject with modified transposition of the great arteries who did not undergo surgery

We describe noncompaction-like remodeling of the anatomical right ventricle (ARV) in a middle-aged subject with modified transposition of the great arteries (TGA). A 54 year-old male had been diagnosed with modified TGA at age 40, but no surgery was performed. Enhanced multislice CT revealed the ascending aorta coursing left of the anterior pulmonary trunk. Furthermore, the myocardium of the ARV appeared thickened, but contrast material could be observed in the ARV myocardium, which resembled noncompaction of the left ventricle (LV). We speculated trabecular development of the ARV, such as a Chiari network, and with TGA, the ARV provided systemic circulation through the aorta. The ARV wall may have thickened due to systemic pressure load, resulting in reduction of wall motion of the ARV on transthoracic echocardiogram. Recent advances in multislice CT imaging have revolutionized the exploration of RV anatomy, especially for depicting the three-dimensional appearance of noncompaction-like remodeling of the ARV in modified TGA in addition to transposition of the great arteries.     

Intrahepatic biliary cysts in children with biliary atresia who have had a Kasai operation

Purpose

In patients with biliary atresia who had undergone a Kasai operation, treatment of intrahepatic biliary cysts (IBCs), particularly when complicated by cholangitis, is often difficult because the clinical implications and the course of IBCs are unclear. Thus, to determine the best treatment guideline, the morphology of IBCs, the clinical course, and the outcomes of such patients were evaluated.

Patients and Methods

A total of 44 patients with type III biliary atresia who underwent a Kasai operation from 1977 to 2005 were postoperatively examined for IBC by using ultrasonography and computed tomography. We classified the IBCs based on their number and shape.

Results

Intrahepatic biliary cysts developed in 12 of 54 patients. Three patients with solitary simple cysts and 1 patient with multiple simple cysts had no history of cholangitis. Two patients with multiple simple cysts had cholangitis at the time of IBC diagnosis and were treated with percutaneous transhepatic cholangiodrainage (PTCD). Patients with simple IBCs did not develop persistent cholangitis and their prognosis depended largely on their liver function; 3 of 6 patients remained healthy without cholangitis, whereas 3 patients required liver transplantation (LT) because of progressive liver failure or worsening hepatopulmonary syndrome, and not severe cholangitis. On the other hand, all 6 patients with multiple complicated IBCs had persistent cholangitis, eventually requiring LT. Even after bile flow to the intestine was reestablished after PTCD, both IBCs and cholangitis recurred. These patients required LT because of severe cholangitis.

Conclusions

Intrahepatic biliary cysts without cholangitis are not a source of infection and require no treatment. Simple IBCs with cholangitis can be controlled by antibiotics and/or PTCD. Patients with multiple complicated IBCs have a poor prognosis, requiring LT to control cholangitis. Although PTCD can control cholangitis in these patients as they wait for LT, PTCD does not alleviate it—LT is the final solution.     

Cerebellar granule cell migration and the effects of alcohol

In the developing brain the majority of neurons migrate from their birthplace to their final destination. This active movement is essential for the formation of cortical layers and nuclei. The impairment of migration does not affect the viability of neurons but often results in abnormal differentiation. The proper migration of neurons requires the orchestrated activities of multiple cellular and molecular events, such as pathway selection, the activation of specific receptors and channels, and the assembly and disassembly of cytoskeletal components. The migration of neurons is very vulnerable to exposure to environmental toxins, such as alcohol. In this article, we will focus on recent developments in the migration of cerebellar granule cells. First, we will describe when, where and how granule cells migrate through different cortical layers to reach their final destination. Second, we will present how internal programs control the sequential changes in granule cell migration. Third, we will review the roles of external guidance cues and transmembrane signals in granule cell migration. Finally, we will reveal mechanisms by which alcohol exposure impairs granule cell migration.     

The new acyl-CoA cholesterol acyltransferase inhibitor SMP-797 does not interact with statins via OATP1B1 in human cryopreserved hepatocytes and oocytes expressing systems

It is possible that SMP-797 will be administered frequently in combination with statins to hyperlipidemic patients. OATP1B1 is thought to be the major transporter that mediates the hepatic uptake of statins. This study investigated whether SMP-797 interacts with statins via OATP1B1 by two approaches. Firstly, the effects of SMP-797 on OATP1B1-mediated uptake of estrone-3-sulfate (ES) by human hepatocytes and by oocytes expressing OATP1B1 were examined. Since OATP1B1-mediated uptake of ES is known to be biphasic (high- and low-affinity sites), concentrations of [(3)H]ES were set lower than the respective K(m) values. Two representative statins were used to assure that statins share OATP1B1 with [(3)H]ES in this in vitro system. Rosuvastatin inhibited OATP1B1-mediated uptake of [(3)H]ES through both sites and pravastatin inhibited a high-affinity site. The inhibition by the positive control (cyclosporin A) was significant. Thus, it is considered that this system was applicable to examine drug-drug interaction with statins on OATP1B1-mediated uptake. In this condition, no apparent inhibition to each site by SMP-797 was observed up to a concentration 3,000-fold higher than the clinical level. Secondly, the uptake of [(14)C]SMP-797 by oocytes expressing OATP1B1 was examined and the activity was negligible. In conclusion, these data suggest that SMP-797 has little potential to interact with statins on OATP1B1.     

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.     

Synergistic T-T cell interaction present in alloreactivity: determination of 'MLR helper' T cell subsets

CD4 and CD8 T cell subsets involved in primary allo-MLR responses were re-evaluated in the present study. The slope analysis of B6 allo-MLR responses to MHC class I-disparate bm1 and class II-disparate bm12 revealed the presence of a T-T cell interaction between CD4 and CD8 T cell subsets. The allo-MLR response of B6 CD4 T cells to bm12 was completely blocked by anti-L3T4, indicating that the function of CD4 T cells is required for allo-MLR responses to bm12. It was further demonstrated that the function of CD8 T cells in class II-disparate allo-MLR is to augment the proliferative response of CD4 T cells. On the other hand, CD8 T cells primarily responded to class I-disparate allo-MLR, and CD4 T cells function to augment the proliferative response of CD8 T cells. It was further indicated that CD4 and CD8 T cells recognize both class I and class II MHC. The CD4 T cell recognition of allo-class I and CD8 T cell recognition of allo-class II induces insufficient signals for proliferation of these T cells. Thus, the class I-reactive CD4 and class II-reactive CD8 T cell subsets function as helper cells ('MLR helper' T cells) for proliferating T cells in MLR responses.     

Chemosensitization by buthionine sulfoximine in vivo

The in vivo effects of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the cytotoxicity of cyclophosphamide (CYM), cisplatin (CDDP) and bleomycin (BLM), were examined by monitoring the changes of non-protein thiols (NPSH) in normal tissues and in the NFSa fibrosarcoma. We used the lung colony assay as a measure of tumor response and the spleen colony assay as a measure of normal tissue response to CYM. In this study, 5 mmol/kg of BSO was subcutaneously injected four times every 12 hr before administration of the above anti-neoplastic drugs. GSH levels in subcutaneous NFSa tumors decreased to 2% of the control 12 hr after the last administration of BSO, but in the bone marrow, had recovered to 41%. In the colony assays, BSO increased the anti-cancer effects of the three chemotherapeutic agents, but did not modify the bone marrow suppression by CYM. This finding was a result of the differential response of GSH depletion in the tumor and in the bone marrow. Our study demonstrates that BSO is an effective chemosensitizer of these drugs and may be of therapeutic value when used at an optimal interval.