Objective-Increased risk of cardiovascular disease in patients with chronic renal failure (CRF) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPCs) may play key roles. We hypothesized that altered EPC biology may contribute to the pathophysiology of CRF. Methods and Results-EPCs were isolated from CRF patients on maintenance hemodialysis (nϭ44) and from a normal control group (nϭ30). CRF patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%) when compared with the controls (PϽ0.001). These findings were corroborated by 30.5% decrease in EPC migratory function in response to vascular endothelial growth factor (VEGF) (Pϭ0. T he lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the most important cause of morbidity and mortality in these patients. 1,2 Even the results of therapeutic strategies such as percutaneous coronary intervention and bypass surgery have shown poor procedural success rates and dismal long-term eventfree survival in CRF patients. 3,4 Most of the increased cardiovascular morbidity and mortality in CRF has been accounted for by the rapid progression of atherosclerosis, which is clinically shown to be accelerated in CRF. 5,6 Experimental studies have also shown that even mild renal dysfunction causes a dramatic acceleration of atherosclerosis. 7 Angiogenesis, which is an essential compensation for myocardial ischemia, is also impaired in CRF. 8 However the mechanism underlying the acceleration of atherosclerosis and impaired angiogenesis by CRF has not been examined closely. Although the phenomenon has been partially explained by the higher prevalence of established risk factors in CRF, such as hypertension, abnormal carbohydrate metabolism, and increased low density lipoprotein (LDL) cholesterol, the extent and severity of cardiovascular disease is clearly disproportionately high relative to the underlying risk factor profile. 9,10 Recent studies have identified that normal adults have a small amount of circulating endothelial progenitor cell (EPC) in the peripheral blood. In response to cytokine stimulation and ischemic insult, these cells are mobilized from bone marrow, home to the ischemic tissue, and contribute to neovascularization and angiogenesis. 11-14 Moreover, EPC is regarded to have a key role in the maintenance of vascular integrity and to act as "repair" cells in response to the endothelial injury, 15,16 which has been regarded as an initial step in atherosclerosis and a result of the actions of various cardiovascular risk factors. 17 Current data suggest that decrease in circulating EPC contributes not only to impaired angiogenesis but also to the progression of atherosclerosis, 18 and patients at risk for coronary artery disease have a decreased number of circulating EPC with impaired activity. 19 -22 Therefore, we reasoned that EPC, which is critical for neovascularization and the maintenance of vascular integrity, Methods Study SubjectsWe...

Ethanol embolization has the potential for cure in the management of AVMs of the body and extremities but with acceptable risk of minor and major complications.

After conservative treatment of SISMAD, we have observed that the majority of patients showed improvement or no change on both angiogram and clinical examination. We believe this observation supports an approach of conservative treatment for patients with SISMAD.

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

ObjectivesTo identify the incidence and the risk factors of emergence agitation in adults undergoing general anesthesia for nasal surgery.MethodsWe retrospectively examined 792 patients aged ≥18 years who underwent general anesthesia for elective nasal surgery between July 2012 and August 2013. Patients in the postanesthesia care unit with a Richmond Agitation Sedation Scale≥+1 at any time were considered to have emergence agitation.ResultsThe overall incidence of emergence agitation is 22.2%. From multivariate regression analysis, the following six variables were found to be significantly associated with emergence agitation (P<0.05): younger age, recent smoking, sevoflurane anesthesia, postoperative pain on the numerical rating scale (NRS)≥5, presence of a tracheal tube, and presence of a urinary catheter. Presence of a tracheal tube was the greatest risk factor, increasing the risk of developing emergence agitation by approximately fivefold (odds ratio, 5.448; 95% confidence interval, 2.973 to 9.982). Younger age was also a strong risk factor (odds ratio, 0.975 for each 1-year increase; 95% confidence interval, 0.964 to 0.987). Current smoking, sevoflurane anesthesia, postoperative pain of NRS≥5, and the presence of a urinary catheter nearly doubled the risk of emergence agitation.ConclusionEmergence agitation following general anesthesia is a common complication in adult nasal surgery patients. To reduce the occurrence and consequences of agitation episodes, elimination of the associated risk factors is necessary, especially in at-risk patients.

Endothelial progenitor cells (EPCs) act as endothelial precursors that promote new blood vessel formation and increase angiogenesis by secreting growth factors and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC transplantation should accelerate the wound-repair process by facilitating neovascularization and the production of various molecules related to wound healing. In a murine dermal excisional wound model, EPC transplantation accelerated wound re-epithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPCtransplanted group exhibited significantly more monocytes/ macrophages in the wound at day 5 after injury than did the EC-transplanted group. This observation is consistent with enzyme-linked immunosorbent assay results showing that EPCs produced in abundance several chemoattractants of monocytes and macrophages that are known to play a pivotal role in the early phase of wound healing. At day 14 after injury, the EPC-transplanted group showed a statistically significant increase in vascular density in the granulation tissue relative to that of the EC-transplanted group. Fluorescence microscopy revealed that EPCs preferentially moved into the wound and were directly incorporated into newly formed capillaries in the granulation tissue. These results suggest that EPC transplantation will be useful in dermal wound repair and skin regeneration, because EPCs both promote the recruitment of monocytes/macrophages into the wound and increase neovascularization. Stem Cells 2005;23:1571-1578

Abstract-Vascular enlargement is a characteristic feature of angiopoietin-1 (Ang1)-induced changes in adult blood vessels. However, it is unknown whether tissues having Ang1-mediated vascular enlargement have more blood flow or whether the enlargement is reversible. We have recently created a soluble, stable and potent Ang1 variant, COMP-Ang1.In the present study, we investigated the effects of varied dose and duration of COMP-Ang1 on vascular enlargement and blood flow in the tracheal microvasculature of adult mice and explored a possible mechanism of long-lasting vascular enlargement. We found that COMP-Ang1 administered by adenoviral vector induced long-lasting vascular enlargement and increased tracheal blood flow. In contrast, short-term administration of COMP-Ang1 recombinant protein induced transient vascular enlargement that spontaneously reversed within a month. In both cases, the vascular enlargement resulted from endothelial proliferation. The COMP-Ang1-induced vascular remodeling is mediated mainly through Tie2 activation. Sustained overexpression of Tie2 could participate in the maintenance of vascular changes. Together, our findings indicate that sustained treatment with COMP-Ang1 can produce long-lasting vascular enlargement and increased blood flow. Key Words: angiopoietin-1 Ⅲ COMP-Ang1 Ⅲ vascular enlargement Ⅲ blood flow A ngiopoietin-1 (Ang1) is known to be a ligand to Tie2 tyrosine kinase receptor expressed on endothelial cells. 1 Ang1/Tie2 signaling is thought be involved in branching and remodeling of the primitive vascular network and in the recruitment of mural cells during development. 2,3 Transgenic overexpression of Ang1 using the skin-specific keratin-14 promoter produces leakage-resistant and enlarged vessels with an increased number of endothelial cells in skin. 4,5 Gene transfer of Ang1 into ischemic tissues produces notably enlarged blood vessels. 6,7 Baffert et al recently identified that Ang1-induced vascular enlargement could be the result of endothelial proliferation in trachea mucosa. 8 Thus, a cardinal feature of Ang1-induced vascular remodeling is vascular enlargement resulting from endothelial cell proliferation in adult animals. 4 -8 Given that Ang1-induced therapeutic benefits correlated with vascular enlargement in the ischemic tissues, 6,7,9 enhanced blood flow through blood vessels enlarged by Ang1 treatment could provide a great therapeutic benefit to ischemic peripheral tissues. However, it is not known whether the tissues having Ang1-mediated enlarged vessels have more blood flow. In addition, the effective dose and treatment period of Ang1 for inducing effective vascular enlargement is not known. Moreover, it is not known whether Ang1-mediated vascular enlargement regresses when Ang1 stimulation is withdrawn.We have recently developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. 10 To create this protein, we replaced the amino-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP). COMP-Ang1 is more po...

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