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.     

Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions

PURPOSE: Amiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actions in vitro and proinflammatory effects in vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg day(-1) orally for seven days before surgery and 45 mg hr(-1) intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers C-reactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery. RESULTS: Ninety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 +/- 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 +/- 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-alpha, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment. CONCLUSION: In the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.     

Die bronchopulmonale Dysplasie Frühgeborener

In very preterm neonates, bronchopulmonary dysplasia (BPD) complicates the course of respiratory distress syndrome, i.e., primary surfactant deficiency in a structural immature lung. In Germany, about 11 000 preterms having a gestational age below 32 weeks are born and treated in neonatal intensive care units per year. Within this high risk group, the rate of BPD is about 15%. Relevant prenatal risk factors include intrauterine inflammatory fetal reaction as a consequence of ascending maternal infections, intrauterine growth retardation apart from the main risk factor immaturity. Postnatal risk factors include genetic predisposition, mechanical ventilation, infections and hemodynamically relevant patent ductus arteriosus.Preventive measures include intratracheal surfactant administration; new studies indicate preventive effects of caffeine, vitamin A and hydrocortisone in a subgroup of neonates with prenatal fetal inflammatory response.Due to long-term detrimental effects of BPD on lung function and psychomotor development, further experimental and clinical studies are mandatory in order to continue to reduce the BPD rate.     

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.     

Tissue engineering: a challenge of today's medicine

During the last years, tissue engineering-based therapies have been introduced in clinical practice in the head and face area. The regeneration of complex tissue structures for all sites of the body is envisioned for the future. In the present situation, specialists of the different fields publish excellent research papers in specialised journals. As a result, the scientific community, seperated towards distinct sub-specialities, has difficulties in communication. To overcome this problem, the demanding, complex and interdisciplinary aspects of tissue engineering has to be approached from new ways. We have conceptualised Head & Face Medicine therefore as a thematically broad ranged journal, including all disciplines involved in the head and neck area. We hope this journal will attract basic researchers and clinicians who are involved in investigating and applying complex themes (examplified by tissue engineering) in the head and face region and will contribute to a gain in scientific information, communication, and collaboration in order to improve the outcome of patient treatments.     

Experimentelle und klinische Studie zur Stabilit?t einer Osteosyntheseplatte für den atrophen Unterkiefer

ZusammenfassungHintergrund Der Anteil an älteren Patienten steigt ständig und damit auch die Zahl traumatischer altersbedingter Verletzungen wie Frakturen des Unterkiefers. Die Frakturversorgung bei älteren Menschen stellt spezielle Anforderungen. Durch das Design einer neu entwickelten Osteosyntheseplatte sollte versucht werden, diese speziellen Gesichtspunkte zu erfüllen.Material und Methoden Im Gegensatz zu den 2.0-Miniplatten (Medartis AG, Basel) besitzt die Pencilbone-2.0-Platte, die aus diesen Miniplatten entwickelt wurde, einen oval geformten Mittelsteg zur Stabilisierung des frakturnahen Knochens und zwei sphärische Gleitlöcher jenseits der Fraktur. An den verstärkten Teil der Osteosyntheseplatte schließen sich jeweils 2 bzw. 3 normale unverstärkte Löcher an, die sich sehr leicht an den frakturfernen Knochen adaptieren lassen. Dies ermöglicht dem Operateur den intraoralen Zugangsweg und eine Handhabung, welche er von der Miniplattenosteosynthese gewohnt ist, bietet aber gleichzeitig eine höhere Stabilität im Vergleich mit den Standard-2.0.-Miniplatten.Ergebnisse und Diskussion Nach experimentellen und biomechanischen Untersuchungen, die alle positive Ergebnisse zeigten, wurde die neue Platte zwischen Oktober 2000 und November 2001 in zwei Kliniken an 16 Frakturen des atrophischen Unterkiefers bei 14 Patienten erfolgreich angewendet. 15 Frakturen heilten primär, lediglich bei einer Fraktur wurde eine neue operative Versorgung wegen Knochendislokation nach erneutem Sturz notwendig.