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Improvements in diabetic microangiopathy after successful simultaneous pancreas-kidney transplantation: a computer-assisted intravital microscopy study on the conjunctival microcirculation.

A computer-assisted intravital microscopy technology has been developed to noninvasively and objectively study diabetic microangiopathy in the conjunctival microcirculation of type-1 diabetics. Quantitative characterization of the conjunctival microcirculation was performed on 12 patients pre- and 18 months postsimultaneous pancreas-kidney transplantation (SPK). Healthy nondiabetic volunteers (n=12), solitary kidney (K) transplanted type-1 diabetics (n=5), and nontransplanted type-1 diabetics (n=12) served as controls. Pre-SPK diabetics showed abnormal-sized venules (diameter=66+/-7 microm) and reduced presence of arterioles (arteriole length/area=18+/-6 microm(-1)) compared with nondiabetic controls (53+/-4 microm; 31+/-8 microm(-1); P<0.05). The computed vascular perfusion capacity of the conjunctival microvasculature was diminished in the same patients (pre-SPK diabetics=49+/-9%; nondiabetic healthy controls=71+/-6%; P<0.05). Significant improvement in microangiopathy was observed in all post-SPK diabetics (diameter=58+/-6 microm; arteriole length/area=26+/-9 microm(-1); vascular perfusion=63+/-8%; P<0.05) 18 months post-SPK. Blood flow velocities in the conjunctival microcirculation in the same post-SPK patients showed noticeable but not significant improvements (nondiabetic controls=2.94+/-0.57 mm/sec; pre-SPK=1.23+/-0.49 mm/sec; post-SPK=1.65+/-0.42 mm/sec). The solitary kidney transplant controls (post-K) showed no significant improvements in diabetic microangiopathy, confirming the unique role of the pancreas in SPK. In general, significant improvements (P<0.05) in diabetic microangiopathy were observed in all 12 diabetics 18 months post-SPK but not in the controls.

Adult↗

Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia.

OBJECTIVE: To characterize microcirculatory actions of activated protein C in an endotoxemia rodent model that allows in vivo studies of microvascular inflammation and perfusion dysfunction. DESIGN: Animal study using intravital microscopy. SETTING: Animal research facility. SUBJECTS: Male Syrian golden hamsters, 6-8 wks old with a body weight of 60-80 g. INTERVENTIONS: In skinfold preparations, endotoxemia was induced by intravenous administration of 2 mg/kg endotoxin (lipopolysaccharide, Escherichia coli). Intravital microscopy allowed quantitative analysis of arteriolar and venular leukocyte adhesion and functional capillary density (cm) that served as a measure of microvascular perfusion failure. Activated protein C (APC group, n = 8, 24 microg/kg intravenously) was substituted continuously during 8 hrs after lipopolysaccharide, whereas endotoxemic buffer-treated animals (control, n = 7) served as controls. MEASUREMENTS AND MAIN RESULTS: Lipopolysaccharide increased leukocyte adhesion and decreased functional capillary density to 50% of baseline values (p <.01 vs. baseline). Activated protein C treatment inhibited (p <.05) lipopolysaccharide-mediated leukocytic response and attenuated (p <.05) endotoxic perfusion failure in nutritive capillaries. CONCLUSIONS: Activated protein C-induced protection from lipopolysaccharide-mediated microcirculatory dysfunction was characterized in vivo for the first time. The impressive modification of leukocyte cross-talk indicates systemic anti-inflammatory activated protein C effects on leukocytes and the endothelium, subsequently improving capillary perfusion. These actions could represent the in vivo mechanism of activated protein C interactions observed in patients with severe sepsis.

Animals↗

Evaluation of nailfold videocapillaroscopic abnormalities in patients with systemic lupus erythematosus.

OBJECTIVE: Nailfold capillaroscopy (NFC) has been shown to have a remarkable value in the differential diagnosis of connective tissue diseases. In fact, NFC patterns reflect the microvascular changes that may play a significant role in pathogenesis. The aims of this study were to determine in patients with systemic lupus erythematosus (SLE) the prevalence of NFC patterns, to evaluate any association with clinical features and laboratory parameters. MATERIALS AND METHODS: One hundred twenty-three patients with SLE were included in this retrospective study. Video NFC parameters were analyzed in each patient. In all cases, the following parameters were evaluated: capillary arrangement, density, size, and shape. RESULTS: In patients with SLE, major capillary abnormalities were frequently observed (44 of 123 = 35.8%); however, no specific pattern was noted. There was a significant correlation between the SLEDAI index and the severity of capillary abnormalities (P < 0.0001). Pathologic capillary abnormalities were also significantly increased in SLE with positive anti-U1-RNP antibodies (P < 0.05). CONCLUSION: NFC may be a useful method to evaluate the microvascular changes in patients with SLE, and the presence of major capillary abnormalities seems to herald a more severe clinical course of the illness.

Adolescent↗

Imaging of the vulnerable plaque: new modalities.

Atherosclerosis is currently considered to be an inflammatory and thus a systemic disease affecting multiple arterial beds. Recent advances in intravascular imaging have shown multiple sites of atherosclerotic changes in coronary arterial wall. Traditionally, angiography has been used to detect and characterize atherosclerotic plaque in coronary arteries, but recently it has been found that plaques that are not significantly stenotic on angiography cause acute myocardial infarction. As a result, newer imaging and diagnostic modalities are required to predict which of the atherosclerotic plaque are prone to rupture and hence distinguish "stable" and "vulnerable" plaques. Intravascular ultrasound can identify multiple plaques that are not seen on coronary angiography. Thermography has shown much promise and is based on the concept that the inflammatory plaques are associated with increased temperature and can also identify "vulnerable patients." Of all these newer modalities, magnetic resonance imaging has shown the most promise in identification and characterization of vulnerable plaques. In this article, we review the newer coronary artery imaging modalities and discuss the limitations of traditional coronary angiography.

Angioscopy↗

A proposed taxonomy for nailfold capillaries based on their morphology.

Certain diseases cause permanent changes to the shapes and densities of nailfold capillaries and, therefore, nailfold capillaroscopy is important as a tool for diagnosing and monitoring these diseases. The first aim of the project is to resolve differences in terminology that have developed over the years in previous work. We propose a taxonomy for nailfold capillaries that cover six descriptive classes: cuticulis, open, tortuous, crossed, bushy, and bizarre. The first three are parametric in that they may be distinguished by the ratio of capillary length to width and by the curvature of the capillary limbs. The last three are characterized by their topology; a crossed capillary has a closed area that is not connected to the image background. Bushy and bizarre capillaries have atypical shapes that are characterized by the convex hull of their skeleton. These descriptive classes may be modified according to anomalies in width and length. The second aim is to automate the classification of capillaries by encapsulating the taxonomy in an algorithm; our computer program rivals the most experienced clinicians in classifying capillaries consistently with an overall agreement of 85% with the clinicians' majority view. This was particularly valuable in classifying borderline shapes objectively and consistently.

Capillaries↗

Interactive virtual endoscopy in coronary arteries based on multimodality fusion.

A novel approach for platform-independent virtual endoscopy in human coronary arteries is presented in this paper. It incorporates previously developed and validated methodology for multimodality fusion of two X-ray angiographic images with pullback data from intravascular ultrasound (IVUS). These modalities pose inherently different challenges than those present in many tomographic modalities that provide parallel slices. The fusion process results in a three- or four-dimensional (3-D/4-D) model of a coronary artery, specifically of its lumen/plaque and media/adventitia surfaces. The model is used for comprehensive quantitative hemodynamic, morphologic, and functional analyses. The resulting quantitative indexes are then used to supplement the model. Platform-independent visualization is achieved through the use of the ISO/IEC-standardized Virtual Reality Modeling Language (VRML). The visualization includes an endoscopic fly-through animation that enables the user to interactively select vessel location and fly-through speed, as well as to display image pixel data or quantification results in 3-D. The presented VRML virtual-endoscopy system is used in research studies of coronary atherosclerosis development, quantitative assessment of coronary morphology and function, and vascular interventions.

Algorithms↗

The pneumatic tourniquet technique for endoscopic radial artery harvest.

BACKGROUND: Endoscopic vessel harvest is viewed as a safe, reliable, and cost-effective method for greater saphenous vein removal. As the radial artery has more recently become a popular conduit choice in coronary artery revascularization, we describe herein an endoscopic technique for radial artery harvest in our first 50 patients as an alternative to the more traditional open technique. METHODS: From November 2001 to July 2002, 54 radial arteries were harvested endoscopically in 50 patients utilizing the VasoView Endoscopic Vessel Harvesting System, an Esmark bandage, and a pneumatic cuff tourniquet. RESULTS: No patients experienced symptoms of vascular compromise, or signs of infection in the donor arm. No adjunctive procedures were required during the vessel harvest, i.e., conversion to open technique. All radial arteries were successfully removed with endoscopic technique and 53 of the 54 radial arteries were successfully used as bypass conduits. Although the quality of the radial artery harvested remains subjective, we found less vasospasm than in our experience with the open technique. Thirty-day follow-up revealed no readmissions, no cardiac ischemic complications, no significant complications with the donor arm, and an excellent cosmetic result. CONCLUSIONS: Endoscopic harvest of the radial artery with the tourniquet technique may offer advantages over the more traditional open technique.

Adult↗

In vivo quantification of the structural abnormalities in psoriatic microvessels before and after pulsed dye laser treatment.

BACKGROUND: Microvascular abnormalities (capillary elongation, widening and tortuosity) are a characteristic feature of psoriasis and form one of the pathological diagnostic criteria. These changes occur early in the progression of a psoriatic plaque, before there is clinical or histological evidence of epidermal hyperplasia. Treatment of psoriatic microvessels with a pulsed dye laser (PDL) has been associated with both clinical improvement and clearance of lesions. OBJECTIVES: To quantify the structural vascular abnormalities in plaque skin using noninvasive techniques in vivo. Investigations were carried out before and after PDL treatment to determine the nature of laser-induced microvascular changes and the relationship between these changes and clinical improvement. METHODS: Plaque microvessels were visualized using native capillaroscopy. Plaques were then treated three times with the PDL at 14-day intervals. Native capillaroscopy was repeated at 2 and 6 weeks after the final laser treatment. Images were analysed using a combination of nonstereological and stereological measurements. RESULTS: Whole body disease was stable. Treated plaques showed a 48% reduction in plaque severity score (P < 0.01). Native studies showed that the PDL significantly reduced plaque microvessel density (P < 0.05), image area fraction (P < 0.01), microvessel length density (P < 0.01) and vessel image width (P < 0.01). The reduction in plaque severity score (which denoted clinical improvement) was related quantitatively to the reduction in microvessel area per unit area of plaque skin, i.e. the image area fraction (correlation coefficient = 0.772, P < 0.01). The greatest response of plaque microvessels was within 2 weeks after the final laser treatment, while the greatest reduction in plaque severity score occurred between 2 and 6 weeks after the final laser treatment, i.e. clinical improvement was preceded by microvascular improvement. CONCLUSIONS: These findings indicate that there is a close correlation between the state of the superficial vasculature and the clinical status of psoriasis. The expanded superficial microvascular bed in plaque skin is a necessary component for maintaining clinical lesions and these blood vessels are thus a legitimate target for treatment.

Adult↗

Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.

BACKGROUND: Neutrophil apoptosis and phagocytic clearance have been proposed as key determinants affecting the resolution of airway inflammation. Objective To determine the kinetics of neutrophil priming, recruitment, activation and subsequent clearance in a naturally occurring equine disease model of neutrophilic pulmonary inflammation. METHODS AND RESULTS: A 5 h mouldy hay/straw challenge in hypersensitive horses induced transient pulmonary dysfunction lasting 4 days. At 24 h circulating neutrophils were primed and displayed delayed rates of spontaneous apoptosis in vitro. Neutrophil numbers in the airspaces peaked at 5 h and then fell abruptly, returning to pre-challenge levels by 4 days. Airspace neutrophils demonstrated increased respiratory burst activity compared with circulating cells and equine neutrophil elastase 2A concentrations increased in parallel with neutrophil numbers indicating in vivo priming and degranulation. The number of apoptotic neutrophils and proportion of alveolar macrophages containing phagocytosed apoptotic neutrophils increased significantly at 24 h and 4 days post-challenge corresponding to the period of most rapid neutrophil clearance. CONCLUSION: This is the first demonstration of spontaneous neutrophil apoptosis and phagocytic removal in a natural disease model of airway inflammation and provides critical kinetic data to support the hypothesis that this clearance pathway plays a central role in the resolution of neutrophilic inflammation.

Allergens↗

The prognostic value of nailfold capillary changes for the development of connective tissue disease in children and adolescents with primary raynaud phenomenon: a follow-up study of 250 patients.

To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective tissue disease. We concluded that there were no specific capillary changes predictive for future development of systemic lupus erythematosus, juvenile onset rheumatoid arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in children and adolescents with Raynaud phenomenon. Most of our study subjects with Raynaud phenomenon who developed these diseases had normal capillary findings or nonspecific changes. Children and adolescents who developed scleroderma spectrum disorders showed a sclerodermatous type of capillary changes 6 months before the expression of the disease, indicating that this type of capillary changes in children and adolescents with Raynaud phenomenon highly correlated with further development of scleroderma spectrum disorders.

Adolescent↗

Endoscopy-assisted radiofrequency ablation around the coronary sinus ostium in dogs: its effects on atrioventricular nodal properties and ventricular response during atrial fibrillation.

INTRODUCTION: Radiofrequency ablation of the slow pathway can prolong atrioventricular (AV) nodal properties and RR intervals during atrial fibrillation (AF) in many patients with AV nodal reentrant tachycardia. However, it is not well elucidated whether these changes are related to the presence of dual AV nodal pathway physiology. The aim of this study was to evaluate changes of AV nodal properties and RR intervals during AF caused by ablation of two specific areas in dogs. METHODS AND RESULTS: Assisted by fiberoptic endoscopy, linear lesions were created between the coronary sinus ostium and tricuspid valve annulus (area 1) or posterior to the ostium (area 2) in 15 dogs. Three additional dogs served as controls. The measurements were made under autonomic blockade. Catheter ablation could be assisted in all dogs by means of endoscopy. Linear lesions were confirmed at autopsy. AV nodal parameters and RR intervals showed no overall changes. Individual data showed that ablation of area 1 resulted in modification of AV nodal properties in 54.5% (facilitation in 36.3% and inhibition in 18.2%), whereas ablation of area 2 induced changes in 50% (facilitation in 10% and inhibition in 40%). The RR intervals were shortened in 33.3% and 20% and prolonged in 44.5% and 40% after ablation of areas 1 and 2, respectively. The RR intervals during AF correlated well with the Wenckebach cycle length and the AV node functional refractory period before and after ablation (r = 0.78 to 0.94, P < 0.01 for each). CONCLUSIONS: Ablation of the two specific areas around the coronary sinus ostium was equally effective in modifying AV nodal properties and the ventricular response during AF without dual AV nodal pathway physiology. The ventricular rate to AF after ablation correlated well with the residual AV nodal properties.

Angioscopy↗

Antithrombin and thrombolytic effects of a new antithrombin agent: angioscopic and angiographic comparison with heparin or batroxobin.

The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.

Angiography↗

Aortic root endoscopy in pediatric cardiac operations for aortic valvuloplasty.

We use aortic root endoscopy for assessment of the aortic valve in pediatric patients. A flexible fiberscope inserted through the ascending aorta provides clear and precise visualization of the aortic valve. This technique of endoscopic assessment will help to judge the cusp prolapse and malcoaptation of the aortic valve in pediatric aortic surgery.

Angioscopy↗