Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.     

RhD表型阴性分子机制的研究

我们对76名中国汉族RhD阴性个体的RHD基因全长编码区进行序列分析，初步探讨中国人D阴性的分子背景，报道如下。     

High-resolution computed tomography in patients with atypical ‘cardiac‘ chest pain: a study investigating patients at 10-year cardiovascular risks defined by the Framingham and PROCAM scores

Background and objective Atypical ‘cardiac‘ chest pain (ACCP) is not usually caused by myocardial ischaemia. Current noninvasive investigations for these symptoms are not yet as accurate as invasive coronary angiography. The latest 64-row multi-detector computed tomography (MDCT) technology is non-invasive, has high specificity and negative predictive values for the detection of significant coronary disease. Our aim was to investigate if this modality can provide more information in the assessment of outpatients with ACCP in addition to established cardiovascular risk scores. Methods Seventy consecutive patients presenting to the outpatient clinic with ACCP underwent 64-row MDCT scan of the coronary arteries. They were categorized into low, medium or high risk groups based upon the Framingham and PROCAM scores. We defined a clinically abnormal MDCT scan as coronary stenosis =50% or calcium score ＞400 Agatston. Results Fifty-three (75.7%) patients did not have clinically abnormal scans. Framingham score classified 43 patients as low-risk while PROCAM classified 59 patients as low-risk. MDCT scans were abnormal for 18.6% and 22.0% of the respective low-risk group of patients. For patients with medium-to-high risk, 33.3% and 36.4% of Framingham and PROCAM patient groups respectively had abnormal MDCT scans. Conclusion MDCT adds valuable information in the assessment of patients with ACCP by identifying a significant proportion of patients categorized as low-risk to have underlying significant coronary stenosis and coronary calcification by established cardiovascular risk scores.     

Feasibility and accuracy of coronary imaging in elderly patients using the 64-row multi-detector computed tomography: a correlation study with conventional coronary angiography

Background Elderly patients generally have higher occurrence of coronary calcification, increased heart rate and difficulty with prolonged breath-holding. The aim of our study was to investigate the feasibility and accuracy of using 64-row multi-detector computed tomography (MDCT) in the assessment of coronary artery stenoses in elderly patients. Methods One hundred and fifty two patients with suspected or known coronary artery disease were divided into 4 groups according to their age (Group A: 40-49 years, n=34; Group B: 50-59 years, n=57; Group C: 60-69 years, n=48; Group D: 70 years and above; n=13). Coronary CT angiography (CTA) using a 64-row MDCT was performed and the findings were compared with that of conventional coronary angiography (CCA). Using axial images, multi-planar reconstructions (MPR) and maximum intensity projections (MIP), coronary segments of lumen diameter = 1.5mm were analyzed for the presence of significant stenosis (= 50% ). Results Percentages of poor image quality from coronary CTA preventing reliable correlations with CCA were 21%, 14%, 19% and 62% in Groups A to D respectively. Patients in Group D had significantly higher calcium scores compared with the other groups (P<0.001). In patients where CTA images were of acceptable quality, percentages of accurate correlations with CCA were 89.8%, 93.4%, 86.6% and 78.0% for Groups A to D respectively. There were no significant difference in serum creatinine, heart rate and contrast volume between the 4 groups. Conclusions The 64-row MDCT coronary angiography was less accurate and feasible for patients aged 70 years or above due to heavy coronary calcification and inability to perform a satisfactory breath-hold. However, a high diagnostic accuracy with the MDCT is possible in patients aged less than 70 years.(J Geriatric Cardiol 2006;3(1):9-14)     

In vivo tumor imaging using a novel RNAi-based detection mechanism

A new concept of tumor imaging is introduced using a siRNA-based probe that is capable of amplifying a specific endogenous fluorescence emission in cancerous tissue. In previous studies, we demonstrated a significant downregulation of Ferrochelatase (FECH) mRNA-expression in colorectal carcinomas leading to the accumulation of protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis. In this article, we report on first in vivo experiments in xenografted nude mice using folate-coupled liposomes or dendritic polyglycerolamine nanoparticles carrying ferrochelatase-siRNA to enhance PpIX-derived fluorescence in the tumor tissue. Tiny tumor foci could be monitored by the emission of PpIX fluorescence in vivo. Due to the omnipresence of the heme synthesis pathway, targeted application of ferrochelatase-siRNA may provide a general means for molecular imaging.From the Clinical EditorA new concept of tumor imaging is presented in this paper using a siRNA-based probe detecting protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis previously demonstrated to accumulate in cancer tissue.     

Impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular beds: a PET-CT study

To evaluate the effect of age, gender and cardiovascular risk factors on vessel wall inflammation and the calcified plaque burden in different vascular beds as assessed by PET/CT. 315 patients (mean age: 57.8 years, 123 male and 192 female) who underwent whole body 18F-FDG PET/CT examinations were included in the study. Blood pool-corrected standardised uptake value (TBR) and the calcified plaque score (CPS, grade 0–4) were determined in the thoracic and abdominal aorta, both common carotid and both iliac arteries. The following cardiovascular risk factors were documented: Age ≥65 years (n = 114), male gender (n = 123), diabetes (n = 15), hyperlipidemia (n = 62), hypertension (n = 76), body mass index (BMI) ≥ 30 (n = 38), current smoker (n = 32). Effects of risk factors on TBR and CPS in different arterial beds were assessed using multivariate regression analysis. In the thoracic aorta TBR was independently associated with age ≥65 years and male gender, CPS was independently associated with age ≥65 years, male gender, hypertension and diabetes. In the abdominal aorta, TBR was independently associated with age ≥65 years and male gender, CPS with age ≥65 years, diabetes and smoking. Independent associations in the carotid arteries were found for age ≥65 years, male gender and BMI ≥ 30 in TBR and for age ≥65 and diabetes in CPS. In the iliac arteries, TBR was independently associated with age ≥65 and CPS with age ≥65, male gender, hypertension, diabetes and smoking. Findings of this PET/CT study demonstrate that the impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular territories. Overall, CPS was more closely associated with cardiovascular risk factors compared to TBR.     

Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes

Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro. The resistance against apoptotic stimuli of these cells hints at a viral survival function in addition to a proliferation-stimulating activity. Here we describe the up-regulation of the antiapoptotic HIAP-1/CIAP-2 gene as a consistent phenotype of HTLV-1-transformed and ATL-derived cultures and its stimulation by the viral oncoprotein Tax. Cotransfections revealed a 60-fold increase of HIAP-1 promoter activity mediated by Tax mainly via nuclear factor-kappaB (NF-kappaB) activation. To address the relevance of virally increased HIAP-1 levels for the survival of HTLV-1-transformed cells, its expression was RNA interference (RNAi) suppressed using a lentiviral transduction system. This resulted in a dramatic reduction of cell growth, a strong induction of apoptosis rates, and increased caspases 3/7 activity, which is known to be suppressed by HIAP-1. Thus, the Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1-transformed lymphocytes. Moreover, this points to HIAP-1 as an important target of the HTLV-1-mediated NF-kappaB activation.