RESUMO
BACKGROUND AND PURPOSE: Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy. METHODS: All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively. RESULTS: A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046). CONCLUSIONS: Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group). METHODS: In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years). RESULTS: Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0-1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%). CONCLUSIONS: In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit-risk ratio.
Assuntos
Hemorragia Cerebral/etiologia , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Terapia Trombolítica/mortalidade , Terapia Trombolítica/estatística & dados numéricos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) is effective when performed within 6â h of symptom onset in selected stroke patients ('Tâ <â 6H'). Its safety and efficacy is unclear when the patient has had symptoms for more than 6â h ('Tâ >â 6H') or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. METHODS: Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0-2] or mortality 3â months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. RESULTS: Six-hundred and fifty-four patients were treated before (Tâ <â 6H) and 205 after 6â h or an unknown time (128 Tâ >â 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in Tâ <â 6H patients, vertebrobasilar occlusion was more common in Tâ >â 6H and UOS patients, and middle cerebral artery occlusions less common in Tâ >â 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. CONCLUSIONS: Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6â h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.
Assuntos
Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/prevenção & controle , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Idoso , Procedimentos Endovasculares/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest. METHODS: From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively. RESULTS: There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2-3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2-3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91â =â 86% and 64/78â =â 82%) compared with pharmacological thrombolysis only (15/32 = 47%; Pâ <â 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0-2] in 54/28% patients and moderate (mRS 0-3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (Pâ =â 0.001). In multivariate analysis age [odds ratio (OR)â =â 0.96, 95% confidence interval (CI)â =â 0.93-0.98], NIHSS on admission (ORâ =â 0.9, 95% CIâ =â 0.83-0.98) and functional ICA-T occlusion (ORâ =â 0.35, 95% CIâ =â 0.16-0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (ORâ =â 9.30, 95% CIâ =â 2.03-42.63). CONCLUSIONS: The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.
Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna/efeitos dos fármacos , Trombólise Mecânica , Terapia Trombolítica , Trombose das Artérias Carótidas/patologia , Artéria Carótida Interna/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reperfusão , Fatores de Risco , Resultado do TratamentoRESUMO
The horse, like the majority of animal species, has a limited amount of species-specific expressed sequence data available in public databases. As a result, structural models for the majority of genes defined in the equine genome are predictions based on ab initio sequence analysis or the projection of gene structures from other mammalian species. The current study used Illumina-based sequencing of messenger RNA (RNA-seq) to help refine structural annotation of equine protein-coding genes and for a preliminary assessment of gene expression patterns. Sequencing of mRNA from eight equine tissues generated 293,758105 sequence tags of 35 bases each, equalling 10.28 gbp of total sequence data. The tag alignments represent approximately 207 × coverage of the equine mRNA transcriptome and confirmed transcriptional activity for roughly 90% of the protein-coding gene structures predicted by Ensembl and NCBI. Tag coverage was sufficient to refine the structural annotation for 11,356 of these predicted genes, while also identifying an additional 456 transcripts with exon/intron features that are not listed by either Ensembl or NCBI. Genomic locus data and intervals for the protein-coding genes predicted by the Ensembl and NCBI annotation pipelines were combined with 75,116 RNA-seq-derived transcriptional units to generate a consensus equine protein-coding gene set of 20,302 defined loci. Gene ontology annotation was used to compare the functional and structural categories of genes expressed in either a tissue-restricted pattern or broadly across all tissue samples.
Assuntos
Cavalos/genética , Anotação de Sequência Molecular , Proteínas/genética , Animais , Feminino , Expressão Gênica , Masculino , Especificidade de Órgãos , RNA Mensageiro/genética , Análise de Sequência de RNARESUMO
Spontaneous dural arterio-venous fistulas can imperceptibly develop over a long time period before they suddenly develop symptoms like bruit, loss of vision, exophthalmos and conjunctival injection. We present the rare case of an occult, para-infectious, dural arterio-venous fistula which became symptomatic after endoscopic sinus surgery. Conjunctival injection and slight exophthalmos developed due to decompensation of venous drainage probably by intraoperative positioning of the patient, positive pressure ventilation and nasal packing.
Assuntos
Seio Cavernoso/patologia , Seio Cavernoso/cirurgia , Malformações Vasculares do Sistema Nervoso Central/patologia , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Endoscopia/métodos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Crystallization of macromolecules for structural studies has long been a hit-or-miss process. The crystallization of hexanucleotides as Z-DNA was studied, and it was shown that the cation concentration for crystal formation could be predicted from solvation free energy (SFE) calculations. Solution studies on the conformation and solubilities of the hexanucleotides showed that a critical concentration of the DNA in the Z-conformation must be present in solution to effect crystallization. The SFE calculations therefore predict the propensity of the hexanucleotides to adopt the left-handed conformation and the driving force required to reach this critical concentration relative to the intrinsic solubility of Z-DNA for crystallization.
Assuntos
DNA/química , Oligodesoxirribonucleotídeos/química , Sequência de Bases , Cátions , Cristalografia , DNA/ultraestrutura , Modelos Moleculares , Conformação de Ácido Nucleico , Espectrofotometria UltravioletaRESUMO
Intravenous thrombolysis (IVT) is the evidence-based treatment of acute ischemic stroke in the first 3 h after symptom onset (IVT 3-4.5 h: off-label use with informed consent of the patient). However, intra-arterial thrombolysis (IAT) results in higher recanalization rates of the middle cerebral artery compared to IVT. Therefore it seems reasonable to apply IAT in addition or instead of IVT up to 6 h after symptom onset.
Assuntos
Fibrinolíticos/administração & dosagem , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Terapia Trombolítica/métodos , Terapia Trombolítica/tendências , HumanosRESUMO
This article provides an overview on the actual state of the interventional neuroradiological management of carotid cavernous fistulas depending on their anatomy and pathophysiology. The results are based on our experience gained during the treatment of patients with complex CCF during the last 15 years. Indications, procedures, and results of transarterial, transvenous and combined arteriovenous approaches for balloon occlusion, embolization, coiling and stenting of these lesions are discussed. Progress in this field is constant so that new technical advances are expected to improve the safety and to expand the indications for these procedures in the future.
Assuntos
Fístula Carótido-Cavernosa/diagnóstico , Fístula Carótido-Cavernosa/terapia , Cateterismo/métodos , Angiografia Cerebral/métodos , Embolização Terapêutica/métodos , Procedimentos Cirúrgicos Vasculares/métodos , HumanosRESUMO
OBJECTIVES: Diffusion-weighted MRI is sensitive to molecular motion and has been applied to the diagnosis of stroke. Our intention was to investigate its usefulness in patients with brain tumor and, in particular, in the perilesional edema. METHODS: We performed MRI of the brain, including diffusion-weighted imaging and mapping of the apparent diffusion coefficient (ADC), in 16 patients with brain tumors (glioblastomas, low-grade gliomas and metastases). ADC values were determined by the use of regions of interest positioned in areas of high signal intensities as seen on T2-weighted images and ADC maps. Measurements were taken in the tumor itself, in the area of perilesional edema and in the healthy contralateral brain. RESULTS: ADC mapping showed higher values of peritumoral edema in patients with glioblastoma (1.75 x 10(-3)mm(2)/s) and metastatic lesions (1.61 x 10(-3)mm(2)/s) compared with those who had low-grade glioma (1.40 x10(-3)mm(2)/s). The higher ADC values in the peritumoral zone were associated with lower ADC values in the tumor itself. CONCLUSIONS: The higher ADC values in the more malignant tumors probably reflect vasogenic edema, thereby allowing their differentiation from other lesions.
Assuntos
Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/patologia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: To determine the accuracy of automated vessel-segmentation software for vessel-diameter measurements based on three-dimensional contrast-enhanced magnetic resonance angiography (3D-MRA). METHOD: In 10 patients with high-grade carotid stenosis, automated measurements of both carotid arteries were obtained with 3D-MRA by two independent investigators and compared with manual measurements obtained by digital subtraction angiography (DSA) and 2D maximum-intensity projection (2D-MIP) based on MRA and duplex ultrasonography (US). In 42 patients undergoing carotid endarterectomy (CEA), intraoperative measurements (IOP) were compared with postoperative 3D-MRA and US. RESULTS: Mean interoperator variability was 8% for measurements by DSA and 11% by 2D-MIP, but there was no interoperator variability with the automated 3D-MRA analysis. Good correlations were found between DSA (standard of reference), manual 2D-MIP (rP=0.6) and automated 3D-MRA (rP=0.8). Excellent correlations were found between IOP, 3D-MRA (rP=0.93) and US (rP=0.83). CONCLUSION: Automated 3D-MRA-based vessel segmentation and quantification result in accurate measurements of extracerebral-vessel dimensions.
Assuntos
Estenose das Carótidas/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Angiografia por Ressonância Magnética/métodos , Validação de Programas de Computador , Idoso , Análise de Variância , Angiografia Digital , Estenose das Carótidas/cirurgia , Meios de Contraste , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento , Ultrassonografia Doppler DuplaRESUMO
BACKGROUND: The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%. OBJECTIVE: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions. METHODS: 294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors. RESULTS: sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH. CONCLUSIONS: With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos , Doença Aguda , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: For patients with cerebral vasospasm refractory to medical and hemodynamic therapies, endovascular therapies often remain the last resort. Data from studies in large cohorts on the efficacy and safety of multiple immediate endovascular interventions are sparse. Our aim was to assess the feasibility and safety of multiple repeat instant endovascular interventions in patients with cerebral vasospasm refractory to medical, hemodynamic, and initial endovascular interventions. MATERIALS AND METHODS: This was a single-center retrospective study of prospectively collected data on patients with cerebral vasospasm refractory to therapies requiring ≥3 endovascular interventions during the course of treatment following aneurysmal subarachnoid hemorrhage. The primary end point was functional outcome at last follow-up (mRS ≤2). The secondary end point was angiographic response to endovascular therapies and the appearance of cerebral infarctions. RESULTS: During a 4-year period, 365 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Thirty-one (8.5%) met the inclusion criteria. In 52 (14%) patients, ≤2 endovascular interventions were performed as rescue therapy for refractory cerebral vasospasm. At last follow-up, a good outcome was noted in 18 (58%) patients with ≥3 interventions compared with 31 (61%) of those with ≤2 interventions (P = .82). The initial Hunt and Hess score of ≤2 was a significant independent predictor of good outcome (OR, 4.7; 95% CI, 1.2-18.5; P = .03), whereas infarcts in eloquent brain areas were significantly associated with a poor outcome (mRS 3-6; OR, 13.5; 95% CI, 2.3-81.2; P = .004). CONCLUSIONS: Repeat instant endovascular intervention is an aggressive but feasible last resort treatment strategy with a favorable outcome in two-thirds of patients with refractory cerebral vasospasm and in whom endovascular treatment has already been initiated.
Assuntos
Procedimentos Endovasculares/métodos , Vasoespasmo Intracraniano/cirurgia , Adulto , Idoso , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Resultado do Tratamento , Vasoespasmo Intracraniano/etiologiaRESUMO
BACKGROUND AND PURPOSE: General anesthesia during endovascular treatment of acute ischemic stroke may have an adverse effect on outcome compared with conscious sedation. The aim of this study was to examine the impact of the type of anesthesia on the outcome of patients with acute ischemic stroke treated with the Solitaire stent retriever, accounting for confounding factors. MATERIALS AND METHODS: Four-hundred one patients with consecutive acute anterior circulation stroke treated with a Solitaire stent retriever were included in this prospective analysis. Outcome was assessed after 3 months by the modified Rankin Scale. RESULTS: One-hundred thirty-five patients (31%) underwent endovascular treatment with conscious sedation, and 266 patients (69%), with general anesthesia. Patients under general anesthesia had higher NIHSS scores on admission (17 versus 13, P < .001) and more internal carotid artery occlusions (44.6% versus 14.8%, P < .001) than patients under conscious sedation. Other baseline characteristics such as time from symptom onset to the start of endovascular treatment did not differ. Favorable outcome (mRS 0-2) was more frequent with conscious sedation (47.4% versus 32%; OR, 0.773; 95% CI, 0.646-0.925; P = .002) in univariable but not multivariable logistic regression analysis (P = .629). Mortality did not differ (P = .077). Independent predictors of outcome were age (OR, 0.95; 95% CI, 0.933-0.969; P < .001), NIHSS score (OR, 0.894; 95% CI, 0.855-0.933; P < .001), time from symptom onset to the start of endovascular treatment (OR, 0.998; 95% CI, 0.996-0.999; P = .011), diabetes mellitus (OR, 0.544; 95% CI, 0.305-0.927; P = .04), and symptomatic intracerebral hemorrhage (OR, 0.109; 95% CI, 0.028-0.428; P = .002). CONCLUSIONS: In this single-center study, the anesthetic management during stent retriever thrombectomy with general anesthesia or conscious sedation had no impact on the outcome of patients with large-vessel occlusion in the anterior circulation.
Assuntos
Anestesia Geral , Isquemia Encefálica/cirurgia , Sedação Consciente , Remoção de Dispositivo/métodos , Procedimentos Endovasculares/métodos , Stents , Acidente Vascular Cerebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo/efeitos adversos , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Trombectomia/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6 hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. METHODS: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. RESULTS: 76 patients (33.0%) presented within 3 hours, 69 (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6 hours did not undergo arteriography and thrombolysis, mostly because of mild (n=44) or rapidly improving neurological deficits (n=13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n=7), limiting comorbidty (n=7) and baseline international normalized ratio>1.7 (n=1). CONCLUSIONS: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6 hours time window and mild or rapidly improving symptoms.
Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Resultado do Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intra-Arteriais/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: Recent studies have focused on mechanical thrombectomy as a means to reduce the time required for revascularization and increase the revascularization rate in acute stroke. To date no systematic evaluation has been made of the different mechanical devices in this novel and fast-developing field of endovascular interventions. To facilitate such evaluations, we developed a specific in vivo model for mechanical thrombectomy that allows visualization of dislocation or fragmentation of the thrombus during angiographic manipulation. METHODS: Angiography and embolization with a preformed thrombus was performed in 8 swine. The thrombus was generated by mixing 25 IU bovine thrombin and 10 mL autologous blood. For visualization during angiography, 1 g barium sulfate was added. RESULTS: The preformed thrombus exhibited mechanical stability, reproducibility, and high radiographic absorption, providing excellent visibility during angiography. The setting allowed selective embolization of targeted vessels without thrombus fragmentation. Despite the application of barium sulfate no local or systemic reaction occurred. Histologic evaluation revealed no intimal damage caused by the thrombus or contrast agent washout. CONCLUSION: The model presented here allows selective and reliable thromboembolization of vessels that reproduce the anatomic and hemodynamic situation in acute cerebrovascular stroke. It permits visualization of the thrombus during angiography and intervention, providing unique insight into the behavior of both thrombus and device, which is potentially useful in the development and evaluation of mechanical clot retrieval in acute cerebrovascular stroke.
Assuntos
Modelos Animais de Doenças , Trombose Intracraniana/cirurgia , Acidente Vascular Cerebral/cirurgia , Trombectomia , Doença Aguda , Angiografia , Animais , Angiografia Cerebral , Trombose Intracraniana/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , SuínosRESUMO
PURPOSE: We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS: Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS: The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION: MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Estudos ProspectivosRESUMO
The gene-to-drug quest will be most directly served by the discovery and development of small molecules that bind to nucleic acids and modulate gene expression at the level of transcription and/or inhibit replication of infectious agents. Full realization of this potential will require implementation of a complete suite of modern drug discovery technologies. Towards this end, here we describe our initial results with a new assay for identification and characterization of novel nucleic acid binding ligands. It is based on the well recognized property of stabilization of hybridization of complementary oligonucleotides by groove and/or intercalation binding ligands. Unlike traditional thermal melt methodologies, this assay is isothermal and, unlike gel-based footprinting techniques, the assay also is performed in solution and detection can be by any number of highly sensitive, non-radioisotopic modalities, such as fluorescence resonance energy transfer, described herein. Thus, the assay is simple to perform, versatile in design and amenable to miniaturization and high throughput automation. Assay validation was performed using various permutations of direct and competitive binding formats and previously well studied ligands, including pyrrole polyamide and intercalator natural products, designed hairpin pyrrole-imidazole polyamides and furan-based non-polyamide dications. DNA specific ligands were identified and their DNA binding site size and sequence preference profiles were determined. A systematic approach to studying the relationship of binding sequence specificity with variation in ligand structure was demonstrated, and preferred binding sites in longer DNA sequences were found by pseudo-footprinting, with results that are in accord with established findings. This assay methodology should promote a more rapid discovery of novel nucleic acid ligands and potential drug candidates.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Ácidos Nucleicos/genética , Ácidos Nucleicos/metabolismo , Pareamento de Bases , Sequência de Bases , Ligação Competitiva , Pegada de DNA , Dactinomicina/metabolismo , Distamicinas/metabolismo , Transferência de Energia , Fluorescência , Substâncias Intercalantes/metabolismo , Cinética , Ligantes , Netropsina/metabolismo , Hibridização de Ácido Nucleico , Ácidos Nucleicos/química , Nylons/metabolismo , Oligonucleotídeos/química , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Regiões Promotoras Genéticas/genética , Pirróis/metabolismo , Reprodutibilidade dos Testes , Soluções , Especificidade por Substrato , Temperatura , TermodinâmicaRESUMO
OBJECTIVE: We examined long-term outcomes of patients with in-stent restenosis (ISR) who underwent different percutaneous interventions at the discretion of individual operators: balloon angioplasty (BA), repeat stent or rotational atherectomy (RA). We also examined long-term outcomes of patients with ISR who underwent coronary artery bypass surgery (CABG). BACKGROUND: In-stent restenosis remains a challenging problem, and its optimal management is still unknown. METHODS: Symptomatic patients (n = 510) with ISR were identified using cardiac catheterization laboratory data. Management for ISR included BA (169 patients), repeat stenting (117 patients), RA (107 patients) or CABG (117 patients). Clinical outcome events of interest included death, myocardial infarction, target vessel revascularization (TVR) and a combined end point of these major adverse cardiovascular events (MACE). Mean follow-up was 19+/-12 months (range = 6 to 61 months). RESULTS: Patients with ISR treated with repeat stent had significantly larger average post-procedure minimal lumen diameter compared with BA or RA (3.3+/-0.4 mm vs. 3.0+/-0.4 vs. 2.9+/-0.5, respectively, p < 0.05). Incidence of TVR and MACE were similar in the BA, stent and RA groups (39%, 40%, 33% for TVR and 43%, 40%, 33% for MACE, p = NS). Patients with diabetes who underwent RA had similar outcomes as patients without diabetes, while patients with diabetes who underwent BA or stent had worse outcomes than patients without diabetes. Patients who underwent CABG for ISR, mainly because of the presence of multivessel disease, had significantly better outcomes than any percutaneous treatment (8% for TVR and 23% for MACE). CONCLUSIONS: In this large cohort of patients with ISR and in the subset of patients without diabetes, long-term outcomes were similar in the BA, repeat stent and RA groups. Tissue debulking with RA yielded better results only in diabetic patients. Bypass surgery for patients with multivessel disease and ISR provided the best outcomes.
Assuntos
Doença das Coronárias/complicações , Doença das Coronárias/cirurgia , Complicações do Diabetes , Stents , Angioplastia Coronária com Balão , Aterectomia Coronária , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: This study sought to determine whether infrapopliteal transcatheter interventions can salvage ischemic limbs in diabetic patients referred for below the knee amputation at our institution. BACKGROUND: The value of transcatheter interventions in diabetic crural arteries is controversial. Tissue oxygen partial pressure (TCO2) levels < 40 mm Hg predict poor wound healing. METHODS: Percutaneous interventions were performed in 29 consecutive diabetic patients in need of limb salvage. Technical success was defined as < 20% residual vessel stenosis. Clinical success was defined as the avoidance of amputation and achievement of wound healing. At hospital discharge, patients were treated with Coumadin and aspirin. Ankle-brachial index (ABI) and TCO2 measurements were obtained before and after the intervention. RESULTS: After 12-month follow-up, six patients had presistent wounds, whereas 23 experienced wound healing. Forty of the 50 infrapopliteal arteries successfully dilated were occluded, with a mean (+/-SD) lesion length of 18.0 +/- 3.5 cm. After the procedure, TCO2 improved from 27.82 +/- 9.97 mm Hg (95% confidence interval [CI] 23.95 to 31.69) to 54.5 +/- 14.73 mm Hg (95% CI 48.79 to 60.21, p < 0.0001), whereas the ABI did not (p > 0.2). TCO2 predicted procedural and clinical success (p < 0.0182). CONCLUSIONS: Infrapopliteal transcatheter interventions in diabetic patients may salvage the majority of limbs doomed to amputation. Although TCO2 measurements are valuable in predicting wound healing and success after interventions, ABI measurements are not.