Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Chromogranin A: friend or foe of the failing myocardium?

Chronic heart failure is defined as the inability of the heartto meet the circulatory demands of the organism. While cardiacinjury, e.g. of ischaemic, toxic, metabolic, or genetic cause,is the initial abnormality, secondary changes occur over thecourse of the disease affecting most organ systems. This leadsto a variety of pathologic changes including endothelial, pulmonary,hepatic, renal, endocrine and skeletal muscle abnormalities,and the state of multi-organ impairment in chronic heart failureis now considered the syndrome of chronic heart failure.¹ A neuroendocrine activation has been described early in     

The frozen elephant trunk technique for the treatment of extensive thoracic aortic aneurysms: operative results and follow-up.

OBJECTIVE: The 'frozen' elephant trunk technique allows for single-stage repair of combined aortic arch and descending aortic aneurysms using a 'hybridprosthesis' with a stented and a non-stented end. This report summarizes the operative- and follow-up data (mean follow-up 14 months) with this new treatment. METHODS: Between 09/01 and 4/04, 22 patients (62+/-9 years; 9 female) with different aortic pathologies (15 aortic dissections, 7 aneurysms) were operated on after approval from the local institutional review board. The stented end of the hybridprosthesis was deployed in the descending aorta through the opened aortic arch during hypothermic circulatory arrest and selective antegrade cerebral perfusion. RESULTS: All patients survived the procedure but one patient died of acute hemorrhage due to rupture of the false lumen in the descending aorta on the second postoperative day. Two patients required reexploration of the chest for bleeding complications. In 2 of 4 patients who developed neurological dysfunction, symptoms resolved completely. In one of them, the descending aorta was perforated intraoperatively due to misplacement of the stented end of the hybridprosthesis. In all follow-up CT-scans thrombus formation in the descending aortic aneurysm excluded by the stented end of the hybridprosthesis has been observed. CONCLUSIONS: This procedure is performed through median sternotomy and combines the concepts of the elephant trunk operation and endovascular stenting of descending aortic aneurysms. Favourable intraoperative and postoperative results during follow-up with regard to thrombus formation around the stented descending aortic segment encourage us to evaluate all patients with thoracic aneurysms extending to proximal and distal of the left subclavian artery for this treatment.     

Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes.

BACKGROUND: Reactive oxygen species play a major role in the development of endothelial dysfunction. It is as yet unspecified whether increased oxidative stress contributes to endothelial dysfunction of the renal vasculature in patients with type 2 diabetes. METHODS: Renal haemodynamics were studied in 20 patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and 20 non-diabetic hypertensive patients at baseline and following infusions of the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg); the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg). RESULTS: The response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42 ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73 m(2); P = NS) was not different between diabetic and non-diabetic patients. In contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33 ml/min/1.73 m(2); P<0.05). CONCLUSIONS: The difference in the response of renal perfusion to an antioxidant suggests increased formation of reactive oxygen species and thereby reduced nitric oxide bioavailability in the renal vasculature of patients with type 2 diabetes.     

Tissue engineering of bone for mandibular augmentation in immunocompetent minipigs: preliminary study.

Large mandibular defects caused by trauma, infection or resection of a tumour are still a major problem for plastic and maxillofacial surgeons. The modern concept of tissue engineering combines the osteoinductive effects of osteogenic cells with a suitable scaffold structure to promote differentiation of osteoblasts and optimal matrix production. Critical size mandibular bone defects were therefore made to investigate the osteogenic potential of periosteal cells and a bioabsorbable polymer fleece (Ethisorb 510) in minipigs. Periosteal cells were isolated from four minipigs, expanded in vitro and seeded with fibrin glue into Ethisorb 510 fleeces. Tissue constructs were used to repair critical size mandibular defects and compared with two minipigs with untreated bone defects. Bone healing was evaluated after 90 and 180 days by radiographs and a histological scoring system. The radiographs showed increased radiodensity of defects filled with the cell-fibrin-fleece-constructs compared with the untreated control group after 90 and 180 days in vivo. The defects repaired by the cell-fibrin-scaffolds (180 days in vivo) obtained the highest histological mean score 2.9 (range 2-3), while defects filled by cell-fibrin-scaffolds (90 days in vivo) achieved a mean score of 2.1 (range 2-3). In contrast, the control group (n = 2) scored 1 and 2. The results show that a combination of periosteal cells and polymer fleeces may be a promising approach for clinical mandibular augmentation.     

Ewing's sarcoma of the femur: Prognosis in 69 patients treated by the CESS group

We reviewed the treatment outcome of 69 patients with Ewing's sarcoma of the femur. The patients received chemotherapy according to the CESS 81 (n 14), CESS 86 (n 43), and CESS 91P (n 12) protocols. The 10-year relapse-free survival rates were 36%, 65%, and 65% (p = 0.01). 68 patients received local treatment. The primary tumor was treated by surgery without radiotherapy in 28 patients; 1 developed a local recurrence and 7 metastases. 10 patients received radiotherapy alone; 4 developed metastases and 4 local recurrences and metastases. 30 cases had a combination of surgery and radiotherapy; 7 developed metastases and 1 a local recurrence and metastasis. The survival of patients after radiotherapy alone was worse than that of patients after surgery with/without radiotherapy (p = 0.005). Pathological fractures (n 16) did not influence the prognosis.