Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis

Objective-We previously demonstrated that upregulation of intermediate-conductance Ca2+ -activated K+ channels (KCa 3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of KCa3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. Methods and Results-Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific KCa3.1 blocker TRAM-34. Expression of KCa3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. KCa3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented KCa3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. Conclusion-Blockade of KCa3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. © 2008 American Heart Association, Inc.

Fluid dynamics and platelet deposition in a model arterial stenosis

The objective of this study was to gain further understanding and elucidation of the fluid dynamic factors and flow-induced mechanisms of the thrombogenic process of platelet deposition onto, and possible subsequent embolization from, the walls of an arterial stenosis. This has been accomplished by measurement of the axial dependence of platelet deposition within a modeled arterial stenosis for a transitional flow and a completely laminar flow field. The stenotic region of the model was collagen-coated to simulate a damaged endothelial lining of an artery. Fluid dynamics within a stenosis was studied using qualitative flow visualization, and was further compared to the in vitro platelet deposition studies. Normalized platelet density (NPD) measurements indicate decreased levels of NPD in the high shear throat region of the stenosis for a Reynolds number of 300 and a drastic increase in NPD at the throat for a Reynolds number of 175. This study provides further understanding of the flow dynamic effects on thrombus development within a stenosis. ^

Prosthetic carotid bypass graft for in-stent restenosis performed for post-endarterectomy recurrent stenosis: technical details

Aim. Carotid artery stenting (CAS) is the treatment of choice for recurrent stenosis after carotid endarterectomy (CEA). However a significative incidence of in-stent restenosis could be occurred. Despite classical CEA leads to good results, in selective cases bypass graft may be the best treatment of in-stent restenosis. Case reports. We describe two cases of carotid bypass graft performed to treat a recurrent in-stent stenosis after CAS for post-CEA restenosis. No death and cardiac complication occurred and no cranial nerves impairment was detected. Conclusion. Prosthetic bypass graft is safe and effective in treatment of in-stent recurrent restenosis after CEA restenosis.

Stenosis triggers spread of helical Pseudomonas biofilms in cylindrical flow systems

Biofilms are multicellular bacterial structures that adhere to surfaces and often endow the bacterial population with tolerance to antibiotics and other environmental insults. Biofilms frequently colonize the tubing of medical devices through mechanisms that are poorly understood. Here we studied the helicoidal spread of Pseudomonas putida biofilms through cylindrical conduits of varied diameters in slow laminar flow regimes. Numerical simulations of such flows reveal vortical motion at stenoses and junctions, which enhances bacterial adhesion and fosters formation of filamentous structures. Formation of long, downstream-flowing bacterial threads that stem from narrowings and connections was detected experimentally, as predicted by our model. Accumulation of bacterial biomass makes the resulting filaments undergo a helical instability. These incipient helices then coarsened until constrained by the tubing walls, and spread along the whole tube length without obstructing the flow. A three-dimensional discrete filament model supports this coarsening mechanism and yields simulations of helix dynamics in accordance with our experimental observations. These findings describe an unanticipated mechanism for bacterial spreading in tubing networks which might be involved in some hospital-acquired infections and bacterial contamination of catheters.

Estenosis esofágica. Aplicación de una técnica quirúrgica. Caso clínico

Se presenta el caso clínico de un paciente que presenta estenosis esofágica tras ingesta de caústicos, con disfagia a líquidos por lo que se realizó esofagectomía transhiatal con técnica de tubo gástrico como alternativa para reemplazo esofágico con ascenso mediastinal y yeyunostomía de alimentación, luego del procedimiento presenta fístula a nivel de la anastomosis proximal cervical y derrame pleural que se drena mediante avenamiento pleural bilateral, se maneja de manera conservadora sin desfuncionalización la fistula cervical mediante dren semirígido, con cierre espontaneo y se da de alta al paciente luego de tolerar dieta

Comparison of 1-year outcome in patients with severe aorta stenosis treated conservatively or by aortic valve replacement or by percutaneous transcatheter aortic valve implantation (data from a multicenter Spanish registry)

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies.

Conservative management in very elderly patients with severe aortic stenosis: Time to change?

Despite current recommendations, a high percentage of patients with severe symptomatic aortic stenosis are managed conservatively. The aim of this study was to study symptomatic patients undergoing conservative management from the IDEAS registry, describing their baseline clinical characteristics, mortality, and the causes according to the reason for conservative management. Consecutive patients with severe aortic stenosis diagnosed at 48 centers during January 2014 were included. Baseline clinical characteristics, echocardiographic data, Charlson index, and EuroSCORE-II were registered, including vital status and performance of valve intervention during one-year follow-up. For the purpose of this substudy we assessed symptomatic patients undergoing conservative management, including them in 5 groups according to the reason for performing conservative management [I: comorbidity/frailty (128, 43.8%); II: dementia 18 (6.2%); III: advanced age 34 (11.6%); IV: patients’ refusal 62 (21.2%); and V: other reasons 50 (17.1%)]. We included 292 patients aged 81.5 ± 9 years. Patients from group I had higher Charlson index (4 ± 2.3), higher EuroSCORE-II (7.5 ± 6), and a higher overall (42.2%) and non-cardiac mortality (16.4%) than the other groups. In contrast, patients from group III had fewer comorbidities, lower EuroSCORE-II (4 ± 2.5), and low overall (20.6%) and non-cardiac mortality (5.9%). Patients with severe symptomatic aortic stenosis managed conservatively have different baseline characteristics and clinical course according to the reason for performing conservative management. A prospective assessment of comorbidity and other geriatric syndromes might contribute to improve therapeutic strategy in this clinical setting.

Implantation Of Transcatheter Aortic Valve Prosthesis Through The Ascending Aorta Concomitant With Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass.

Introdution: The transcatheter aortic valve implantation in the treatment of high-risk symptomatic aortic stenosis has increased the number of implants every year. The learning curve for transcatheter aortic valve implantation has improved since the last 12 years, allowing access alternatives. The aim of this study is to approach the implantation of transcatheter aortic valve through transaortic via associated with off-pump cardiopulmonary bypass surgery in a 67-year-old man, with chronic obstructive pulmonary disease, arterial hypertension and kidney transplant. Off-pump coronary artery bypass surgery was performed and the valve in the aortic position was released successfully. There were no complications in the intraoperative and postoperative period. Gradient reduction, effective orifice increasing of the prosthesis and absence of valvular regurgitation after implantation were observed by transesophageal echocardiography. Procedural success demonstrates that implantation of transcatheter aortic valve through the ascending aorta associated with coronary artery bypass surgery without CPB is a new option for these patients.

Plastias de estenoses de intestino delgado na doença de Crohn: resultados imediatos e tardios

BACKGROUND: Strictureplasty is an alternative surgical procedure for Crohn?s disease, particulary in patients with previous resections or many intestinal stenosis. AIM: To analyze surgical complications and clinical follow-up in patients submitted to strictureplasty secondary to Crohn?s disease. METHODS: Twenty-eight patients (57.1% male, mean age 33.3 years, range 16-54 years) with Crohn?s disease and intestinal stenosis (small bowel, ileocecal region and ileocolic anastomosis) were submitted to strictureplasty, at one institution, between September 1991 and May 2004. Thirteen patients had previous intestinal resections. The mean follow-up was 58.1 months. A total of 116 strictureplasties were done (94 Heineke-Mikulicz - 81%, 15 Finney - 13%, seven side-to-side ileocolic strictureplasty - 6%). Three patients were submitted to strictureplasty at two different surgical procedures and two in three procedures. RESULTS: Regarding to strictureplasty, postoperative complication rate was 25% and mortality was 3.6%. Early local complication rate was 57.1%, with three suture leaks (10.7%) and late complication was present in two patients, both with incisional hernial and enterocutaneous fistulas (28.6%). Patients remained hospitalized during a medium time of 12.4 days. Clinical and surgical recurrence rates were 63% and 41%, respectively. Among the patients submitted to another surgery, two patients had two more operations and one had three. Recurrence rate at strictureplasty site was observed in 3.5%, being Finney technique the commonest one. Presently, 19 patients had been asymptomatic with the majority of them under medical therapy. CONCLUSION: Strictureplasties have low complication rates, in spite of having been done at compromised site, with long term pain relief. Considering the clinical course of Crohn?s disease, with many patients being submitted to intestinal resections, strictureplasties should be considered as an effective surgical treatment to spare long intestinal resections.

Resultados da cirurgia de reservatórios ileais em pacientes com doença de Crohn

BACKGROUND: Total rectocolectomy and ileal pouch-anal anastomosis is the choice surgical procedure for patients with ulcerative colitis. In cases of Crohn's disease post-operative diagnosis, it can be followed by pouch failure. AIM: To evaluate ileal pouch-anal anastomosis long-term outcome in patients with Crohn's disease. METHODS: Between February 1983 and March 2007, 151 patients were submitted to ileal pouch-anal anastomosis by Campinas State University Colorectal Unit, Campinas, SP, Brazil, 76 had pre-operative ulcerative colitis diagnosis and 11 had post-operative Crohn's disease diagnosis. Crohn's disease diagnosis was made by histopathological biopsies in nine cases, being one in surgical specimen, two cases in rectal stump, small bowel in two cases, ileal pouch in three and in perianal abscess in one of them. The median age was 30.6 years and eight (72.7%) were female. RESULTS: All patients had previous ulcerative colitis diagnosis and in five cases emergency colectomy was done by toxic megacolon. The mean time until of Crohn's disease diagnosis was 30.6 (6-80) months after ileal pouch-anal anastomosis. Ileostomy closure was possible in 10 cases except in one that had ileal pouch fistula, perianal disease and small bowel involvement. In the long-term follow-up, three patients had perineal fistulas and one had also a pouch-vaginal fistula. All of them were submitted to a new ileostomy and one had the pouch excised. Another patient presented pouch-vaginal fistula which was successfully treated by mucosal flap. Three patients had small bowel involvement and three others, pouch involvement. All improved with medical treatment. Presently, the mean follow-up is 76.5 months and all patients are in clinical remission, and four have fecal diversion. The remaining patients have good functional results with 6-10 bowel movements/day. CONCLUSION: Crohn's disease diagnosis after ileal pouch-anal anastomosis for ulcerative colitis may be usual and later complications such fistulas and stenosis are common. However, when left in situ ileal pouch is associated with good function.

Echocardiographic study of paediatric patients with mucopolysaccharidosis

Principle Mucopolysaccharidosis is an inborn error of metabolism causing glucosaminoglycans tissue storage. Cardiovascular involvement is variable but contributes significantly towards the morbidity and mortality of the patients. Objective To characterise the echocardiographic abnormalities in children and adolescents with different types of mucopolysaccharidosis. Method Echocardiograms and medical records of 28 patients aged 2–14 years, seen from 2003 to 2005, were revised. At that time, the enzymatic replacement therapy was still not available in our institution.Results Echocardiographic alterations were detected in 26 patients (93 per cent), whereas 16 (57 per cent) had abnormal auscultation, and only 6 (21 per cent) presented with cardiovascular complaint. Mitral valve thickening with dysfunction (regurgitation, stenosis, or double lesion) was diagnosed in 60.8 per cent, left ventricular hypertrophy in 43 per cent and aortic valve thickening with regurgitation in 35.8 per cent of the patients. There was no systolic dysfunction and mild left diastolic dysfunction was shown in 21.5 per cent of the patients. Pulmonary hypertension was present in 36 per cent of the patients, causing the only two deaths recorded. There was a strong association between the accumulation of dermatan sulphate and the presence of mitral valve dysfunction (p = 0.0003), aortic valve dysfunction (p = 0.006), and pulmonary hypertension (p = 0.006). Among individuals with two or more examinations, 82 per cent had a worsening evolution. Conclusions Echocardiographic alterations in children with Mucopolysaccharidosis are frequent and have a progressive character Left valve lesions, ventricular hypertrophy, and pulmonary hypertension were the most common findings and there was an association between the accumulation of dermatan sulphate and cardiovascular involvement. Unlike in adults, pulmonary hypertension was the main cause of death, not left ventricle systolic dysfunction

Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery

Background: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of >= 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. Conclusion: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis?

AIM: To evaluate the long-term results of liver resection for the treatment of primary intrahepatic lithiasis. Prognostic factors, especially the impact of bilioenteric anastomosis on recurrence of symptoms were assessed. METHODS: Forty one patients with intrahepatic stones and parenchyma fibrosis/atrophy and/or biliary stenosis were submitted to liver resection. Resection was associated with a Roux-en-Y hepaticojejunostomy in all patients with bilateral stones and in those with unilateral disease and dilation of the extrahepatic biliary duct (> 2 cm). Late results and risk factors for recurrence of symptoms or stones were evaluated. RESULTS: There was no operative mortality. After a mean follow-up of 50.3 mo, good late results were observed in 82.9% of patients; all patients submitted to liver resection alone and 58.8% of those submitted to liver resection and hepaticojejunostomy were free of symptoms (P = 0.0006). Patients with unilateral and bilateral disease showed good late results in 94.1% and 28.6%, respectively (P < 0.001). CONCLUSION: Recurrence of symptoms in patients with hepaticojejunostomy showed that this may not be the ideal solution. Further studies are needed to establish the best treatment for patients with bilateral stones or unilateral disease and a dilated extrahepatic duct. (C) 2010 Baishideng. All rights reserved.

Videodensitometric analysis of advanced carotid plaque: correlation with MMP-9 and TIMP-1 expression

Background: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP (TIMP) promote derangement of the extracellular matrix, which is ultimately reflected in plaque images seen on ultrasound. Videodensitometry can identify structural disturbances in plaques. Objectives: To establish the correlations between values determined using videodensitometry in B-mode ultrasound images of advanced carotid plaques and the total expression of MMP-9 and TIMP-1 in these removed plaques. Methods: Thirty patients underwent ultrasonic tissue characterization of carotid plaques before surgery, using mean gray level (MGL), energy, entropy and homogeneity. Each patient was assigned preoperatively to one of 2 groups: group I, symptomatic patients (n = 16; 12 males; mean age 66.7 +/- 6.8 years), and group II, asymptomatic patients (n = 14; 8 males; mean age 67.6 +/- 6.81 years). Tissue specimens were analyzed for MMP-9 and TIMP-1 expression. Nine carotid arteries were used as normal tissue controls. Results: MMP-9 expression levels were elevated in group II and in normal tissues compared to group I (p < 0.001). TIMP-1 levels were higher in group II than in group I, and significantly higher in normal tissues than in group I (p = 0.039). The MGL was higher in group II compared to group I (p = 0.038). Energy had greater values in group II compared to group I (p = 0.02). There were no differences between patient groups in homogeneity and entropy. Energy positively correlated with MMP-9 and TIMP-1 expression (p = 0.012 and p = 0.031 respectively). Homogeneity positively correlated with MMP-9 and TIMP-1 expression (p = 0.034 and p = 0.047 respectively). There were no correlations between protein expression and MGL or entropy. Conclusions: Videodensitometric computer analysis of ultrasound scanning images can be used to identify stable carotid plaques, which have higher total expression levels of MMP-9 and TIMP-1 than unstable plaques.