Cardiac MRI: Part 2, pericardial diseases

OBJECTIVE: MRI plays an important role in the morphologic and functional evaluation of pericardial diseases. MRI has the advantages of high spatiotemporal resolution, soft-tissue contrast, wide FOV, and multiplanar imaging capabilities, making it a valuable tool in the evaluation of pericardial disorders. In this article, the role of MRI in the evaluation of pericardial disorders, including pericardial constriction, is described and illustrated. CONCLUSION: MRI is a vital diagnostic tool in the evaluation of pericardial diseases, particularly inflammation and constriction, because it can provide both morphologic and functional information essential for determining the optimal therapeutic strategy. It is used for the characterization and delineation of the extent of spread of pericardial masses. Various imaging sequences are available, so the MRI protocol should be optimized and tailored to the specific clinical condition that is being evaluated.     

尾穗苋甲醇提取物对扑热息痛致大鼠肝损伤的保护作用（英文）

目的：检测尾穗苋（Amaranthus caudatus）甲醇提取物对扑热息痛致大鼠肝损伤的保护作用。方法：5组大鼠分别给予羧甲基纤维素钠、扑热息痛、尾穗苋甲醇提取物（200或400mg/kg）并扑热息痛、水飞蓟素并扑热息痛。给药14d后采集大鼠血样进行血液生化检查,而后处死大鼠,收集各组大鼠肝脏组织样本供组织病理学检查。检测的指标包括肝功能标志物如丙氨酸氨基转移酶（alanine aminotransferase,ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase,AST）、血清白蛋白（albumin,ALB）、总蛋白（total protein,TP）、总胆红素（total bilirubin,TB）和直接胆红素（direct bilirubin,DB）及氧化损伤标志物如丙二醛（malondialdehyde,MDA）、还原型谷胱甘肽（reduced glutathione,GSH）、总硫醇（total thiols,TT）和过氧化氢酶（catalase,CAT）。结果：与未治疗组相比,浓度为200和400mg/kg的尾穗苋甲醇提取物均能显著改善由扑热息痛引起的大鼠肝损伤,改善扑热息痛导致的ALT、AST、TB和DB水平升高及血清ALB水平降低（P〈0.01）。与未治疗组相比,浓度为200和400mg/kg的尾穗苋甲醇提取物能够显著降低扑热息痛导致的MDA及TP水平增高（P〈0.01）,并显著升高GSH、CAT及TT水平（P〈0.01）。大鼠肝脏组织病理学检查的结果也证实了尾穗苋甲醇提取物对大鼠肝脏的保护作用。结论：本研究证实了尾穗苋的甲醇提取物对于扑热息痛引起的大鼠肝损伤具有显著的保护作用,证实了其在民族医学中治疗肝病的药用价值。     

Harnessing the Natural Biology of Adeno-Associated Virus to Enhance the Efficacy of Cancer Gene Therapy

Adeno-associated virus (AAV) was first characterized as small “defective” contaminant particles in a simian adenovirus preparation in 1965. Since then, a recombinant platform of AAV (rAAV) has become one of the leading candidates for gene therapy applications resulting in two FDA-approved treatments for rare monogenic diseases and many more currently in various phases of the pharmaceutical development pipeline. Herein, we summarize rAAV approaches for the treatment of diverse types of cancers and highlight the natural anti-oncogenic effects of wild-type AAV (wtAAV), including interactions with the cellular host machinery, that are of relevance to enhance current treatment strategies for cancer.     

Matrix metalloproteinase-9, transforming growth factor-β1, and tumor necrosis factor-α plasma levels in chronic pancreatitis

Objective

The aim of the study was to investigate the plasma levels of matrix metalloproteinase-9 (MMP-9), transforming growth factor-β 1 (TGF-β1), and tumor necrosis factor-α (TNF-α) in chronic pancreatitis (CP).

Methods

Blood samples were obtained from 71 patients with CP and 100 control subjects, and plasma levels of MMP-9, TGF-β1, and TNF-α were determined by enzyme-linked immunosorbent assay.

Results

The plasma levels of MMP-9 (18.3?±?3.0 ng/mL, p?<?0.0001), TGF-β1 (215.4?±?178.1 ng/mL, p?=?0.0301), and TNF-α (111.2?±?69.3 ng/mL, p?<?0.001) were significantly elevated in CP compared to the control group.

Conclusion

The role of elevated plasma MMP-9, TGF-β1, and TNF-α in CP requires further evaluation.     

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1-associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1-encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1-associated morbidity.     

Association of host pharmacodynamic effects with virologic response to pegylated interferon alfa-2a/ribavirin in chronic hepatitis C

Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ≤3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups. Conclusion: This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response. However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response.     

Contralateral diaphragmatic palsy in acute stroke: An interesting observation

Diaphragmatic palsy in hemiparetic stroke is not well recognized. Further, its implications on stroke outcome have not been studied. Here, we report a patient with left-sided diaphragmatic palsy due to an acute right middle cerebral artery territory infarction. The diagnosis was suspected on finding an elevated dome of the diaphragm on the left side in a routine chest radiograph and was confirmed by finding decreased movements of the left hemidiaphragm on fluoroscopic examination. We hypothesize that this condition is probably under-recognized in clinical practice and its clinical importance not well known. The pathophysiological basis of diaphragmatic palsy in acute stroke and its possible clinical implications are discussed.     

Three chemotherapy studies of tuberculous meningitis in children

Chemotherapy studies were undertaken in 180 patients with tuberculous meningitis. They were treated for 12 months with 1 of 3 regimens: the first consisted of streptomycin, isoniazid and rifampicin daily for the first 2 months, followed by ethambutol plus isoniazid for 10 months; in the second, pyrazinamide was added for the first 2 months, and in the third, rifampicin was reduced to twice weekly in the first 2 months. Steroids were prescribed for all the patients in the initial weeks of treatment. Approximately 50% of the patients were aged less than 3 years. On admission, 13% of the patients were classified as stage I, 77% as stage II and 9% as stage III. Cerebrospinal fluid (CSF) culture results were available for all the 180 patients and M. tuberculosis was isolated in 59 (33%). CSF smear results for acid fast bacilli were available only for the 103 patients admitted to the second and the third studies, and of these in 60 (58%) the CSF was positive either by smear or culture. The response to therapy was similar in the 3 studies. Despite administration of rifampicin for 2 months, the mortality was high. In all, 27% of the patients died of tuberculous meningitis, 39% had neurological sequelae and 34% recovered completely. There was a strong association between the stage on admission and the mortality rate, the deaths being highest in stage III. In the first study, when isoniazid was prescribed daily in a dosage of 20 mg/kg, 39% of the patients developed jaundice; however, when the dosage was reduced to 12 mg/kg, the incidence fell to 16%. In the third study, where rifampicin was administered twice a week, the incidence of jaundice was much lower (5%).