Differential diagnosis of intra- and perilienal tumors by use of a RES-specific MRI contrast agent

PURPOSE: To describe the additional benefit in detection and differential diagnosis of peri- and intrasplenic tumors by use of an superparamagnetic iron oxide contrast agent (SPIO). MATERIALS AND METHODS: We represent 7 patients with known malignant tumors. Aim of the examination was the detection and characterisation of intra- or perisplenic tumors. We performed T2w TSE breath triggered sequences before and 10 min after application of SPIO and T1w Flash 2D GRE sequences before and after SPIO and Gadopentetate dimeglumin application. All images were presented to two radiologists, who were asked to asses the presence and characterisation of tumors by using a five-point confidence scale. RESULTS: In two patient intrasplenic hemangiomas were detected, intrasplenic lymphoma, metastasis was excluded, respectively. In two patients perisplenic tumors were diagnosed as gastrointestinal stroma tumors, confirmed by biopsy. In two patients accessory spleens were identified and lymph node metastasis excluded. In one patient an intrasplenic cyst was diagnosed. SPIO enhanced T2w images and Gadopentetate dimeglumin enhanced T1w sequences were evaluated as superior. CONCLUSION: The examination of the spleen by use of superparamagnetic iron oxides offers additional abilities in depiction and charaterisation of intra- and perisplenic tumors in first experiences. First clinical observations indicate that a combination of SPIO enhanced T2w sequences and Gadopentetate dimeglumin enhanced T1w dynamic sequences might be superior to other sequences in detection and characterisation of splenic tumors.     

Glutathione-S-transferase genotypes, smoking, and their association with markers of inflammation, hemostasis, and endothelial function: the atherosclerosis risk in communities (ARIC) study

Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.     

Experimental examination concerning the efficacy of silver-coated Dacron prostheses in vascular graft infections following subcutaneous implantation in a standardized infection model

It was the aim of the study to examine the efficacy of silver coated prostheses in comparison to Rifampin in impregnated prostheses in the prevention of vascular graft infections. MATERIAL AND METHODS: 24 C3H/HcN mice with a bodyweight between 24 and 27 grams were assigned to four different groups. GROUP I: control gel-sealed Dacron graft (Uni-Graft DV) (6), GROUP II: gel-sealed Dacron graft (Uni-Graft DV) contaminated locally with 2 x 10(7) CFU/1.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP III: silver prosthesis (Intergard Silver) contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP IV: Rifampin impregnated prosthesis contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6). 14 days after primary operation all animals were euthanized and the grafts harvested. Specimens were examined for signs of infections by histology and microbiology. RESULTS: At termination of the trial on day 14 none of the grafts of group I were contaminated. 6 out of 6 grafts in group II, 6 out of 6 grafts in group III and 1 out of 6 grafts in group IV presented with infected grafts. The use of antimicrobial Rifampin could significantly prevent infection after bacterial challenge in group IV. CONCLUSION: The silver protected prosthesis (Intergard Silver) seems to be not effective in protecting vascular infection in vivo. However, the Rifampin group showed excellent results. In conclusion Rifampin bonded gelatin-sealed Dacron grafts are significantly more resistant to bacteremic infection than are silver/collagen-coated Dacron grafts.     

Ultrastructural examination of cell-mediated degradation of a calcium phosphate ceramic

Up to now little is known about cell-mediated degradation of biomaterial surfaces, especially as methodologically significant studies are not available. Therefore, the present study focused on ultrastructural details of cells involved in degradation of calcium phosphate ceramics. For the experimental procedure six adult sheep were used. At the medial aspect of the left hindlimb a cylindrical defect was created at the level of the proximal epiphysis of the tibia. Subsequently, a calcium phosphate paste was packed into the defect. Six weeks after implantation, specimens from the implants fixed by perfusion were examined histologically and by transmission electron microscopy. The results of light microscopy revealed substitution of the ceramic by newly formed lamellar bone. Electron microscopy indicated multinucleated cells localized at the implantation site and the bone surface, corresponding to osteoclasts. They formed resorption lacunae and revealed typical ultrastructural features such as the ruffled border and the sealing zone. Osteoclast-mediated degradation was performed by simultaneous resorption and phagocytosis. For the first time this degradation mechanism was documented in vivo. It confirms the notion that osteoclasts are members of the monocyte/macrophage family.     

Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.     

Instructions for Authors

Over 10 years ago, the first successful gene therapy paradigms for experimental brain tumors models have been conducted, and they were thought to revolutionize the treatment of patients with gliomas. Application of gene therapy has been quickly forced into clinical trials, the first patients being enrolled in 1994, with overall results being disappointing. However, single patients seemed to benefit from gene therapy showing long-term treatment response, and most of these patients bearing small glioblastomas. Whereas the gene therapy itself has been performed with high sophistication, limited attention has been paid on technologies, which (i) allow an identification of viable target tissue in heterogenous glioma tissue and which (ii) enable an assessment of successful vector administration and vector-mediated gene expression in vivo. However, these measures are a prerequisite for the development of successful gene therapy in the clinical application. As biological treatment strategies such as gene and cell-based therapies hold promise to selectively correct disease pathogenesis, successful clinical implementation of these treatment strategies rely on the establishment of molecular imaging technology allowing the non-invasive assessment of endogenous and exogenous gene expression in vivo. Imaging endogenous gene expression will allow the characterization and identification of target tissue for gene therapy. Imaging exogenously introduced cells and genes will allow the determination of the 'tissue dose' of transduced cell function and vector-mediated gene expression, which in turn can be correlated to the induced therapeutic effect. Only these combined strategies of non-invasive imaging of gene expression in vivo will enable the establishment of safe and efficient vector administration and gene therapy protocols for clinical application. Here, we review some aspects of imaging in gene therapy trials for glioblastoma, and we present a 'proof-of-principle' 2nd-generation gene therapy protocol integrating molecular imaging technology for the establishment of efficient gene therapy in clinical application.