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Transcutaneous carbon dioxide measurement (TcCO2) offers the ability to continuously and non-invasively monitor carbon dioxide (CO2) tensions when end-tidal monitoring is not possible. The accuracy of TcCO2 has not been established in anesthetized apneic patients with obesity. In this secondary publication, we present a methods comparison analysis of TcCO2 with the gold standard arterial PCO2, in adult patients with body mass index (BMI) > 35kg/m2 who were randomized to receive high flow or low flow nasal oxygenation during post-induction apnea. Agreement between PaCO2 and TcCO2 at baseline, the start of apnea and the end of apnea were assessed using a non-parametric difference plot. Forty-two participants had a median (IQR) BMI of 52 (40-58.5) kg/m2. The mean (SD) PaCO2 was 33.9 (4.0) mmHg at baseline and 51.4 (7.5) mmHg at the end of apnea. The bias was the greatest at the end of apnea median (95% CI, 95% limits of agreement) 1.90 mmHg (-2.64 to 6.44, -7.10 to 22.90). Findings did not suggest significant systematic differences between the PaCO2 and TcCO2 measures. For a short period of apnea, TcCO2 showed inadequate agreement with PaCO2 in patients with BMI > 35 kg/m2. These techniques require comparison in a larger population, with more frequent sampling and over a longer timeframe, before TcCO2 can be confidently recommended in this setting.
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Monitorização Transcutânea dos Gases Sanguíneos , Dióxido de Carbono , Adulto , Humanos , Índice de Massa Corporal , Monitorização Transcutânea dos Gases Sanguíneos/métodos , Apneia , Obesidade/complicaçõesRESUMO
BACKGROUND: Evidence is lacking regarding the efficacy of Optiflow transnasal humidified rapid-insufflation ventilator exchange (THRIVE™) in obese patients. We compared the impact of this technique at 70 L min-1 with 4 L min-1 oxygen via nasal prongs on safe apnoea times of paralysed obese patients. METHODS: We randomised adults with a BMI >35 kg m-2 undergoing elective bariatric surgery. While apnoeic and paralysed, Group T received 70 L min-1 oxygen via Optiflow THRIVE™. Group N received nasal prong oxygen at 4 L min-1. The primary outcome was time to SpO2 ≤95% while apnoeic, with a 360 s cut-off. This was analysed by applying a time-to-event analysis. RESULTS: Forty-two patients were included. The median (inter-quartile range) BMI was 44.8 kg m-2 (40.0-50.0) in Group T and 42.0 kg m-2 (39.3-45.1) in Group N. Median (inter-quartile range) time to SpO2 ≤95% in Group T was 356 (165 to ≥360) s and in Group N, 210 (160-270) s. Using a survival analysis framework, median time-to-event in Group T was 356 s (95% confidence interval 165 s-upper limit not defined) and 210 s (95% confidence interval 160-242 s) (P=0.049) in Group N. CONCLUSIONS: Compared with oxygen delivered via nasal prongs at 4 L min-1, oxygen delivery via Optiflow THRIVE™ at a flow rate of 70 L min-1 can prolong safe apnoea time, however, the results are statistically inconclusive. Optiflow THRIVE™ did decrease the rate of reduction in Pao2 during apnoea. CLINICAL TRIAL REGISTRATION: ANZCTR 12618000445279.
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Apneia/metabolismo , Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Oxigenoterapia/métodos , Adulto , Feminino , Humanos , Insuflação/métodos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigênio/metabolismo , Paralisia/fisiopatologia , Troca Gasosa Pulmonar , Fatores de TempoRESUMO
BACKGROUND: Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity. METHODS: Participants had a body mass index (BMI) ≥45 kg/m2 and underwent laparoscopic bariatric surgery. FC and INV measurements were obtained simultaneously every 5 min on each patient, following induction of anesthesia. Agreement over time was assessed using modified Bland-Altman plots and error grid analysis permitted clinical interpretation of the results. Four-quadrant plots allowed assessment of concordance in blood pressure changes. RESULTS: The 30 participants had a median (IQR) BMI of 50.2 kg/m2 (IQR 48.3-55.3). The observed bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 14.3 mmHg (14.1, -13.4 - 42.0), 5.2 mmHg (10.9, -16.0 - 26.5) for mean arterial pressure (MAP) and 2.6 mmHg (10.8, -18.6 - 23.8) for diastolic blood pressure (DBP). Error grid analysis showed that the proportion of readings in risk zones A-E were 90.8, 6.5, 2.7, 0 and 0% for SBP and 91.4, 4.3, 4.3, 0 and 0% for MAP, respectively. Discordance occurred in ≤8% of pairs for consecutive change in SBP, MAP and DBP. CONCLUSIONS: The vascular unloading technique was not adequately in agreement with radial arterial monitoring. Evaluation in a larger sample is required before recommending this technique for intraoperative monitoring of patients with BMI ≥45 kg/m2.
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Determinação da Pressão Arterial/instrumentação , Determinação da Pressão Arterial/métodos , Monitorização Intraoperatória/instrumentação , Monitorização Intraoperatória/métodos , Obesidade/cirurgia , Artéria Radial/fisiologia , Adulto , Idoso , Cirurgia Bariátrica , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Designing peripheral arterial stents has proved challenging, as implanted devices will repetitively and unpredictably deform and fatigue during movement. Preclinical testing is often inadequate, given the lack of relevant animal models. The purpose of this study was to test the hypothesis that deformation of the human peripheral vasculature could be qualitatively and quantitatively modeled using an experimental animal. METHODS: Anteroposterior contrast angiography was performed in domestic Landrace-Yorkshire farm pigs. Images were obtained with the hind limbs naturally extended then repeated, (1) flexed approximately 90° at the hip and knee, (2) overflexed in a nonphysiological fashion. Quantitative vascular angiographic analysis was utilized to measure arterial diameter, length, and deformation. Percent axial arterial compression and bending were assessed. RESULTS: Eight iliofemoral arteries in four animals were imaged. Mean luminal diameters of the iliac and femoral segments in the neutral position were 5.4 ± 0.5 mm and 4.6 ± 0.5 mm. Hind limb physiologic flexion induced profound arterial compression, 17 ± 8% and 29 ± 6% and bending, 36°±10° and 76° ± 13° within the iliac and femoral segments, respectively. With extreme flexion, the femoral artery could be reliably bent >90°. The observed findings exceeded the deformation observed historically within the human superficial femoral (â¼5% compression and 10° bending) and popliteal artery (â¼10% compression and 70° bending). CONCLUSIONS: Significant nonradial deformation of the porcine iliofemoral arteries was observed during manual hind limb flexion and exceeded that typically observed in humans. This model constitutes a "worst case" scenario for testing deformation and fatigue of intravascular devices indicated for the human peripheral vasculature.
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Artéria Femoral/fisiologia , Teste de Materiais/métodos , Artéria Poplítea/fisiologia , Desenho de Prótese , Falha de Prótese , Angiografia , Animais , Fenômenos Biomecânicos , Meios de Contraste/administração & dosagem , Procedimentos Endovasculares/instrumentação , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Membro Posterior/irrigação sanguínea , Membro Posterior/fisiologia , Humanos , Masculino , Modelos Animais , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Amplitude de Movimento Articular/fisiologia , Stents , Estresse Mecânico , Sus scrofa , Doenças Vasculares/cirurgiaRESUMO
Absorbable metallic implants have been under investigation for more than a century. Animal and human studies have shown that magnesium (Mg) alloys can be safely used in bioresorbable scaffolds. Several cardiovascular and orthopedic biodegradable metallic devices have recently been approved for use in humans. Bioresorbable Mg implants present many advantages when compared to bioabsorbable polymer or nonabsorbable metallic implants, including similar strength and mechanical properties as existing implant-grade metals without the drawbacks of permanence or need for implant removal. Imaging visibility is also improved compared to polymeric devices. Additionally, with Mg-based cardiovascular stents, the risk of late stent thrombosis and need for long-term anti-platelet therapy may be reduced as the host tissue absorbs the Mg degradation products and the morphology of the vessel returns to a near-normal state. Absorbable Mg implants present challenges in the conduct of preclinical animal studies and interpretation of pathology data due to their particular degradation process associated with gas production and release of by-products. This article will review the different uses of Mg implants, the Mg alloys, the distinctive degradation features of Mg, and the challenges confronting pathologists at tissue collection, fixation, imaging, slide preparation, evaluation, and interpretation of Mg implants.
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Ligas/efeitos adversos , Materiais Biocompatíveis/efeitos adversos , Segurança de Equipamentos/métodos , Magnésio/efeitos adversos , Teste de Materiais/métodos , Próteses e Implantes/efeitos adversos , Ligas/química , Animais , Materiais Biocompatíveis/normas , Segurança de Equipamentos/instrumentação , Imageamento Tridimensional , Magnésio/química , Teste de Materiais/instrumentação , Próteses e Implantes/normasRESUMO
Blood pressure monitoring plays a key part in the preoperative, intraoperative, and postoperative care of all patients. In patients with obesity, hypertension indicates increased metabolic and surgical risk and may signal the presence of significant medical comorbidities, including obstructive sleep apnea. Avoidance of hypertension postoperatively is necessary to minimize bleeding risk after surgery. Hypotension in the postoperative period may be the first sign of significant complications that require urgent management. With the problem of being overweight or obese now affecting two-thirds of adults in Western countries, the proportion of patients with obesity in perioperative environments is similarly increasing. Detection of aberrations in blood pressure is contingent on the accuracy of blood pressure measurement methods. Patients with obesity tend to have a large arm circumference and "cone-shaped arms." Standard blood pressure cuffs fit such patients poorly, and this compromises the accuracy of measurements. Alternatives to arm blood pressure cuffs, some made specifically for individuals with obesity, have been evaluated but are not widely available to clinicians. This focused narrative review will discuss the relevance of hypertension management in the care of patients with obesity, highlight the currently available methods for perioperative monitoring of blood pressure, and explore the opportunities that exist to improve the perioperative blood pressure care in patients with obesity undergoing surgical procedures.
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Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Assistência Perioperatória/métodos , Idoso , Determinação da Pressão Arterial/normas , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/cirurgia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/cirurgia , Assistência Perioperatória/normasRESUMO
Objective: Recanalization with balloon angioplasty and/or self-expanding stents (SES) has become the endovascular treatment of choice for symptomatic femoropopliteal occlusive disease. These strategies generate suboptimal clinical results, however, because they fail to expand the artery fully and ineffectively prevent recoil, neointimal hyperplasia, and restenosis. Balloon-expandable stents, given their greater radial force and rigid structure, represent a more effective treatment strategy, but only short lengths can be implanted safely in arteries that deform and bend with skeletal motion. The purpose of this preclinical experiment was to test the hypothesis that simultaneous implantation of a series of short, resorbable, balloon-expandable, paclitaxel-eluting scaffolds would prevent neointimal hyperplasia and stenosis compared with SES in an animal model of percutaneous femoropopliteal intervention. Methods: We extruded 6 × 60 mm Efemoral Vascular Scaffold Systems (EVSS) from copolymers of poly-L-lactic acid, coated with paclitaxel 3 µg/mm2, crimped onto a single delivery balloon, and implanted percutaneously into the iliofemoral arteries of eight Yucatan mini-swine. We implanted 7- to 8-mm × 60 mm SES into the contralateral experimental arteries. The animals were serially imaged with contrast angiography and optical coherence tomography after 30, 90, 180, 365, and 730 days. The primary end point of this study was neointimal morphometry over time. Secondary end points included acute deformation and angiographic and optical coherence tomography-derived measurements of chronic vascular response. Results: Over the 2-year study period, one SES was found to be completely occluded at 90 days; all EVSS were widely patent at all time points. Arteries treated with SES exhibited profound neointimal hyperplasia with in-stent stenosis. In contrast, arteries treated with EVSS exhibited only modest vascular responses and minimal stenosis. After 2 years, the mean neointimal thickness (0.45 ± 0.12 vs 1.31 ± 0.91 mm; P < .05) and area (8.41 ± 3.35 vs 21.86 ± 7.37 mm2; P < .05) were significantly decreased after EVSS implantation. By 2 years, all scaffolds in all EVSS-treated arteries had resorbed fully. Conclusions: In this preclinical animal model of peripheral endovascular intervention, the EVSS decreased neointimal hyperplasia and stenosis significantly compared with SES, then dissolved completely between the first and second years after implantation.
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BACKGROUND: Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes. METHOD: Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic ß-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours. RESULTS: After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect. CONCLUSION: After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.
Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/terapia , Stents Farmacológicos , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Angiografia Coronária , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Reestenose Coronária/prevenção & controle , Vasos Coronários/patologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Everolimo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Necrose , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Sirolimo/administração & dosagem , Suínos , Fatores de Tempo , Cicatrização/efeitos dos fármacosRESUMO
Symptomatic femoropopliteal occlusive disease has been increasingly treated using endovascular methods. However, restenosis, especially after implantation of permanent metallic stents, has remained common. To date, resorbable scaffolds have failed to achieve sufficient radial strength to enable the successful treatment of long, mobile, peripheral arteries. In the present nonsurvival, large animal experiment, a novel device consisting of multiple, short, serial, balloon-expandable, bioresorbable scaffolds was deployed in arteries subjected to supraphysiologic deformation. Compared with native vessels, the scaffolded arteries continued to bend (113° ± 19° vs 110° ± 20°; P = .10) and shorten (15% ± 15% vs 20% ± 14%; P = .16), unencumbered by the placement of the investigational device. The mean luminal diameter of the scaffolded arteries was preserved without kinks or occlusions in exaggerated flexion (4.7 ± 0.7 vs 4.7 ± 0.5 mm in extension vs flexion; P = .80). Arterial deformation was borne by shortening of the interscaffold spaces (2.2 ± 0.8 mm vs 1.9 ± 0.7 mm in extension vs flexion; P < .01) and the scaffolds themselves (10.7 ± 1.4 mm vs 9.9 ± 1.1 mm in extension vs flexion; P < .01). The results from the present study challenge the perceived limitations of balloon-expandable devices implanted in peripheral mobile arteries. We have presented a bioresorbable scaffold that combines sufficient radial strength to preserve the mean luminal diameter with movement and the flexibility to accommodate femoropopliteal deformation.
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The degradation of Mirage Bioresorbable Microfiber Scaffold was evaluated in vitro and in vivo. The degradation in polymer molecular weight (MW), strut morphology, and integrity was accessed using gel permeation chromatography (GPC), X-ray micro-computed tomography (micro-CT) evaluation. To simulate the physiological degradation in vitro, scaffolds were deployed in silicone mock vessels connected to a peristaltic pumping system, which pumps 37°C phosphate-buffered saline (PBS, pH 7.4) at a constant rate. At various time points (30D, 60D, 90D, 180D, 270D, and 360D), the MW of microfibers decreased to 57.3, 49.8, 36.9, 13.9, 6.4, and 5.1% against the baseline. The in vivo degradation study was performed by implanting scaffolds in internal thoracic arteries (ITAs) of mini-swine. At the scheduled sacrifice time points (30D, 90D, 180D, 270D, 360D, and 540D), the implanted ITAs were excised for GPC analysis; the MW of the implanted scaffolds dropped to 58.5, 34.7, 24.8, 16.1, 12.9, and 7.1, respectively. Mass loss of scaffolds reached 72.4% at 540D of implantation. Two stages of hydrolysis were observed in in vitro and in vivo degradation kinetics, and the statistical analysis suggested a positive correlation between in vivo and in vitro degradation. After 6 months of incubation in animals, significant strut degradation was seen in the micro-CT evaluation in all sections as strut fragments and separations. The micro-CT results further confirmed that every sample at 720D had X-ray transmission similar to surrounding tissue, thereby indicating full degradation within 2 years. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1842-1850, 2018.
Assuntos
Implantes Absorvíveis , Prótese Vascular , Teste de Materiais , Artérias Torácicas , Microtomografia por Raio-X , Animais , Masculino , Suínos , Porco Miniatura , Artérias Torácicas/diagnóstico por imagem , Artérias Torácicas/cirurgiaRESUMO
BACKGROUND AND PURPOSE: The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. METHODS: We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. RESULTS: The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test (P=0.39) or Spearman test (P=0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. CONCLUSIONS: USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Ferro , Imageamento por Ressonância Magnética/métodos , Óxidos , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Dextranos , Feminino , Óxido Ferroso-Férrico , Humanos , Inflamação/diagnóstico por imagem , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade , Radiografia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Fatores de TempoRESUMO
OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day). The study started in November 2006 and concluded in August 2010. All subjects underwent 2 brain structural magnetic resonance imaging (MRI) scans, at baseline and at the end of the trial. Structural MRI images had been processed using the automated pipeline for longitudinal segmentation and surface reconstruction implemented in FreeSurfer. The primary outcome measure of this post hoc study was the annualized percentage change (APC) of cortical thickness. RESULTS: The donepezil group exhibited reduced APC cortical thinning compared to placebo in the rostral anterior cingulate (right: P = .048; left: P = .032), the orbitofrontal (right: P = .012; left: P < .048), and the right inferior frontal (P = .022) cortices and in the right insula (P = .010). These results were not statistically significant after Bonferroni correction likely due to insufficient power for cortical thickness measurements in the study group powered for the predefined hippocampus outcome. CONCLUSIONS: Our findings support the hypothesis that cortical thickness is a reliable candidate surrogate outcome in early predementia AD trials. In addition, donepezil treatment may have an impact on cortical structure/morphology in areas innervated by the medial and lateral cholinergic pathways. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00403520.
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Doença de Alzheimer/tratamento farmacológico , Amnésia/tratamento farmacológico , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/tratamento farmacológico , Progressão da Doença , Indanos/farmacologia , Nootrópicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Piperidinas/farmacologia , Sintomas Prodrômicos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Amnésia/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Disfunção Cognitiva/diagnóstico por imagem , Donepezila , Método Duplo-Cego , Feminino , Humanos , Indanos/administração & dosagem , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Nootrópicos/administração & dosagem , Piperidinas/administração & dosagemRESUMO
Smoking is a major risk factor for atherosclerotic diseases. However, the impact of cigarette smoke exposure on neovascularization that develops in response to tissue ischemia is unknown. Here we demonstrate that cigarette smoke extracts inhibit hypoxia-induced in vitro angiogenesis (matrigel assay) in human umbilical vascular endothelial cells. In vivo, mice exposed to cigarette smoke (MES) were shown to have a significant impairment of angiogenesis following surgically induced hindlimb ischemia. The reduced angiogenic response in MES was documented by Laser Doppler flow perfusion studies and capillary density analyses in ischemic hindlimbs. Inhibition of angiogenesis by cigarette smoke in vitro and in vivo was associated with a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in hypoxic conditions. Administration of an adenoviral vector encoding for HIF-1alpha/VP16, a hybrid transcription factor that is stable in hypoxic and normoxic conditions, restored VEGF expression and completely reversed the cigarette smoke inhibition of angiogenesis in hypoxic conditions. Taken together, these results suggest that cigarette smoke exposure impairs angiogenesis by inhibiting VEGF through decreased expression of HIF-1alpha in hypoxic conditions.
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Fatores de Crescimento Endotelial/antagonistas & inibidores , Linfocinas/antagonistas & inibidores , Neovascularização Fisiológica , Fumar/efeitos adversos , Fatores de Transcrição/antagonistas & inibidores , Adenoviridae/genética , Animais , Hipóxia Celular , Endotélio Vascular/citologia , Endotélio Vascular/crescimento & desenvolvimento , Vetores Genéticos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Modelos Biológicos , Transdução de Sinais , Fatores de Transcrição/genética , Transfecção , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Although durable polymer coated drug-eluting stents (DES) are standard care in percutaneous coronary interventions, new stent platforms employing biodegradable polymer based drug delivery are increasingly being used in clinical practice. AIM: To evaluate the short- (28 days) and medium-term (90 days) vascular effects of the new biodegradable polymer coated sirolimus-eluting stent - the PROLIM stent. METHODS: The objectives of the study were evaluated using standard angiographic and histological methods. In addition, the mechanical integrity of tested stents was assessed using Faxitron imaging. A total of 12 PROLIM stents, 11 biodegradable polymer only coated stents (BPCS), and 12 bare metal stents (BMS) were implanted in the coronary arteries of 16 female non-atheroslerotic domestic swine using an overstretch of 1.1:1.0. RESULTS: At 28 days, neointimal proliferation was significantly lower in the PROLIM and BMS stents compared to the BPCS stents (p ≤ 0.05). Interestingly, despite thin neointima found at this time in the PROLIM group, there was a further significant decrease in neointimal formation between 28 and 90 days (p = 0.04). Although a statistically bigger neointima was found in BPCS stents at 28 days compared to the PROLIM and BMS stents, there was a 50% decrease in the neointimal area at 90 days follow-up (p = 0.02) which reached the level seen in other groups. The endothelialisation was completed in all tested stents after 28 days. There was a significant increase of fibrin depositions in the PROLIM treated arteries at 28 days which were resorbed nearly completely at 90 days follow-up. At 28 days, the inflammatory response was found to be numerically higher in the BPCS stents (p = NS) compared to other tested groups. On the contrary, at 90 days follow-up when the degradation process of the polymer had been completed, the inflammatory reaction decreased substantially to the level seen in the PROLIM and BMS stents. Faxitron analysis of the stented arteries revealed no major abnormalities except for isolated strut fractures observed in the mid portions of two BMS stents and one BPCS stent. CONCLUSIONS: The PROLIM - a biodegradable polymer coated sirolimus-eluting stent - demonstrates very good short-term and medium-term angiographic and histological results. The lack of 'catch-up phenomenon', fast endothelialisation process, and minimal inflammatory reaction may contribute to favourable clinical outcomes using PROLIM stents.
Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Stents Farmacológicos , Teste de Materiais , Sirolimo/administração & dosagem , Animais , Materiais Revestidos Biocompatíveis/efeitos adversos , Angiografia Coronária , Vasos Coronários/cirurgia , Stents Farmacológicos/efeitos adversos , Feminino , Técnicas In Vitro , Poliésteres , Desenho de Prótese , Suínos , Vasculite/etiologiaRESUMO
La esclerosis tuberosa, enfermedad de Bourneville, Epiloia de Sherlock, enfermedad de Brushfield-Wyatt, escleroma de Virchow o adenomas sebáceos de Pringle, es un síndrome neurocutáneo que presenta gran variedad de manifestaciones clínicas, patológicas y radiológicas debidas al resultado de malformaciones hemartomatosas multiorgánicas a nivel de la piel, sistema nerviosos central, riñones, aparato cardiovascular, pulmones, ojos, huesos y aparato digestivo. Presentamos una paciente de 33 años con un cuadro de saciedad precoz, disfagia con una masa palpable en hipocondrio y flanco izquierdo. Comparamos los hallazgos en la literatura y concluimos que si bien es infrecuente la asociación de la esclerosis tuberosa con el carcinoma de células renales, existe una participación genética en el desarrollo tumoral renal, siendo aún más rara, la presencia de metástasis hepática
Assuntos
Humanos , Feminino , Adulto , Carcinoma de Células Renais/complicações , Esclerose Tuberosa/complicações , Neoplasias Hepáticas/secundário , Tomografia Computadorizada por Raios X , Esclerose Tuberosa , Esclerose Tuberosa/diagnósticoRESUMO
Objetivo: el propósito de éste estudio es determinar la eficacia de la Tomografía Computada Helicoidal bifásica para predecir la resecabilidad del adenocarcinoma cefálico de páncreas en la invasión de la vena porta y mesentérica superior. Material y métodos: 46 pacientes con diagnóstico de adenocarcinoma cefálico de páncreas que fueron sometidos a una cirugía curativa o paliativa fueron estudiados con Tomografía Computada Helicoidal preoperatoria. El compromiso tumoral de la vena porta y mesentérica superior fue graduada en una escala de 1 a 3, basado en la contigüidad circunferencial del tumor sobre el vaso. Grado 1: sin contacto, grado 2: contacto tumoral con el vaso en menos del 50 por ciento y grado 3: contacto tumoral en más del 50 por ciento. Resultados: el número total de vasos evaluados fue 92. En nuestra serie la TC Helicoidal preoperatoria mostró una corteza diagnóstica del 77 por ciento para la resecabilidad y del 100 por ciento la irresecabilidad. Conclusión: nuestra experiencia estadificando en 3 grados con TC Helicoidal bifásica el compromiso vascular del adenocarcinoma cefálico de páncreas es altamente específica para predecir el tumor irresecable, en pacientes que fueron graduados 2 y 3