Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen

Summary.  Previously we demonstrated that domain 5 (D5) of high-molecular-weight kininogen (HK) inhibits neovascularization in the chicken chorioallantoic membrane (CAM) assay and further found that kallikrein cleaved HK (HKa) inhibited FGF2-and VEGF-induced neovascularization, and thus was antiangiogenic. In this study, we sought to demonstrate whether uncleaved HK stimulates neovascularization and thus is proangiogenic. The chick chorioallantoic membrane was used as an in ovo assay of angiogenesis. Low-molecular-weight kininogen stimulates angiogenesis, indicating that D5 is not involved. Bradykinin stimulates neovascularization equally to HK and LK and is likely to be responsible for the effect of HK. A murine monoclonal antibody to HK (C11C1) also recognizes a similar component in chicken plasma as detected by surface plasmon resonance. Angiogenesis induced by FGF2 and VEGF is inhibited by this monoclonal antibody and is a more potent inhibitor of neovascularization induced by VEGF than an integrin α_vβ₃ antibody (LM 609). Our postulate that C11C1 inhibits the stimulation of angiogenesis by HK was confirmed when either C11C1 or D5 completely inhibited angiogenesis in the CAM induced by HK. Growth of human fibrosarcoma (HT-1080) on the CAM was inhibited by GST-D5 and C11C1. These results indicate HK is proangiogenic probably by releasing bradykinin and that a monoclonal antibody directed to HK could serve as an antiangiogenic agent with a potential for inhibiting tumor angiogenesis and other angiogenesis-mediated disorders.     

Assessment of the efficacy of teriparatide treatment for osteoporosis on lumbar fusion surgery outcomes: a systematic review and meta-analysis

Neurosurgical Review - Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures....     

Anatomic basis of vascular distribution in combined removal of liver and pancreas (28.5.93)

Summary Based on the study of the arterial distribution of 120 hepatic grafts removed from brain-dead patients, the authors assess the possibilities of vascular partition in cases of combined removal of the liver and pancreas. The discussion deals with the vascular distribution of each organ. The presence of a right hepatic artery arising from the superior mesenteric a. (SMA) requires preservation of the SMA with the hepatic graft, while the pancreas is removed with the celiac trunk (CT) and its branches. The presence of a left hepatic artery arising from the CT requires its preservation with the hepatic graft, the pancreas being removed with the SMA and the splenic artery.

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Partage vasculaire des prélèvements hépatiques et pancréatiques combinés : bases anatomiques (28.5.93)

Résumé A partir de l'étude de la distribution artérielle de 120 greffons hépatiques prélevés sur des patients en état de mort cérébrale, les auteurs apprécient les possibilités de partage vasculaire en cas de prélèvement combiné foie-pancréas. La discussion porte sur la distribution vasculaire de chaque organe. L'existence d'une artère hépatique droite naissant de l'artère mésentérique supérieure (AMS) nécessite de conserver l'AMS avec le greffon hépatique, le pancréas est prélevé avec le tronc coeliaque (TC) et ses branches. La présence d'une artère hépatique gauche naissant du TC impose de le conserver avec le greffon hépatique, le pancréas est prélevé avec l'AMS et l'artère splénique.

     

Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis

In the liver, the immunostaining of cytokeratins (CK) 7 and 20 has been used to distinguish usual peripheral cholangiocarcinomas (CC) and colorectal carcinoma metastasis (CRM). However, other subtypes of CC are not infrequent and may be particularly difficult to distinguish from CRM by histology and even immunohistochemistry. Therefore, 48 CC from different locations, either peripheral (n = 19), or nonperipheral, that is, from the large intrahepatic bile ducts, the hilum, and the extrahepatic bile ducts (n = 29), and with different cytoarchitectural patterns were tested for CK7 and CK20 and compared with 31 CRM. CC were positive for CK7 and CK20 in 96% and 70%, respectively, whatever the architecture and differentiation of the tumor. The labeling index (LI) of CK7 in CC was always high, whereas it was low or moderate for CK20. CK20-positive phenotype was significantly more frequent in nonperipheral than in peripheral CC (82% vs 47%; p = 0.007). CRM were all positive for CK20 with a high LI, and mostly negative (81%) for CK7. In conclusion, (1) the CK immunoprofile of CC varies according to the location of the tumor in the biliary tract, peripheral CC being more often CK7+/CK20-, and nonperipheral ones CK7+/CK20+; and (2) a decision tree based on CK20 LI and CK7 positivity allows the distinction of CRM and CC, even for the nonperipheral type.     

Photorealistic imaging of left atrial appendage occlusion/exclusion

Recent improvements in 3D TEE post processing rendering techniques referred to as TrueVue (Philips Medical Systems, Andover, MA, USA). It allows for novel photorealistic imaging of cardiac structures including left atrial appendage (LAA) and its closure devices. Here we present TrueVue images of the LAA prior to and after LAA exclusion/occlusion using various percutaneous and surgical techniques. TrueVue may improve delineation of LAA anatomy prior to occlusion as well as visualization of occluder device position within the LAA.     

Lone Aortic Insufficiency and Conduction Disease: A Marker of Reactive Arthritis

A 48‐year‐old male with history of chronic arthritis and uveitis presented with 1 year of progressively reduced exercise capacity and nonexertional chest pain. Physical examination was consistent with severe aortic insufficiency. An electrocardiogram demonstrated sinus rhythm with first degree atrioventricular block. Transthoracic and transesophageal echocardiography demonstrated severe lone central aortic insufficiency of a trileaflet valve due to leaflet thickening, retraction of leaflet margins and mild aortic root dilation in the setting of left ventricular dilatation. In addition, computed tomographic angiography revealed a small focal aneurysm of the distal transverse arch. He was found to be positive for the immunogenetic marker HLA‐B27. The patient subsequently underwent uncomplicated mechanical aortic valve replacement. The diagnosis of HLA‐B27 associated cardiac disease should be entertained in any individual with lone aortic insufficiency, especially if accompanied by conduction disease.