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1.
AJNR Am J Neuroradiol ; 44(6): 634-640, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37169541

RESUMO

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Falha de Tratamento , Procedimentos Endovasculares/métodos , Embolização Terapêutica/métodos
2.
Neurochirurgie ; 68(2): 202-205, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34186030

RESUMO

Recent studies of the medical literature have revealed numerous and serious problems. Errors in the design, methods and interpretation of studies can frequently be identified. A huge hidden problem is publication bias, the tendency for positive articles to be published, while negative articles are either not written or submitted. This can systematically lead to an overestimation of the value of treatments, of diagnostic or prognostic studies. Even more worrisome is selective reporting: only a subset of a wide array of tested hypotheses are presented (the ones that turned out to be positive with significance testing). This is particularly true for secondary endpoints and subgroup findings, but even the primary endpoints of trials have been modified when publications are compared to protocols. The peer-review process is fallible. Even if it were strengthened, reviewers cannot examine what is not reported. Hence many problems can only be mitigated with better reporting. Numerous initiatives have proposed guidelines to promote transparent reporting, but progress is slow.

3.
AJNR Am J Neuroradiol ; 42(9): 1615-1620, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34326106

RESUMO

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (αK) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (αK = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (αK = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (αK = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (αK = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (αK = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Angiografia , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Reprodutibilidade dos Testes , Instrumentos Cirúrgicos , Resultado do Tratamento
4.
AJNR Am J Neuroradiol ; 41(4): 612-618, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32217551

RESUMO

BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best (κ ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial (κ > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters' judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial (κ ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.


Assuntos
Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , Vasoespasmo Intracraniano/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia
5.
Neurochirurgie ; 65(6): 370-376, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31229533

RESUMO

BACKGROUND AND PURPOSE: Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. METHODS: The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS>2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. RESULTS: An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS>2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%-53%), and 10/34 patients allocated to coiling (29%; 17%-46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%-94%), and 18/27 patients allocated to coiling (67%; 47%-81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%-60%]) than EVT (9/48 [19%; 10%-31%]). CONCLUSION: Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.


Assuntos
Aneurisma Roto/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Angiografia Cerebral , Estudos Cross-Over , Determinação de Ponto Final , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
J Neurol Neurosurg Psychiatry ; 79(1): 91-2, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18079301

RESUMO

After occlusion of flow in an artery, further ischaemic episodes are not expected due to lack of a flow conduit to carry the embolus. In the carotid stump syndrome, ongoing ischaemic events may continue due to collateral flow via the external carotid artery. We report two patients presenting with posterior circulation strokes after documented vertebral artery occlusion, due to a vertebral stump syndrome. Their presentation, the pathophysiology of cervico-vertebral anastomoses and management are described.


Assuntos
Arteriopatias Oclusivas/patologia , Trombose Intracraniana/cirurgia , Artéria Vertebral/patologia , Idoso , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/terapia , Encéfalo/irrigação sanguínea , Cerebelo/irrigação sanguínea , Cerebelo/patologia , Circulação Cerebrovascular/fisiologia , Diplopia/etiologia , Embolização Terapêutica , Lateralidade Funcional/fisiologia , Hemianopsia/etiologia , Humanos , Trombose Intracraniana/complicações , Trombose Intracraniana/patologia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/terapia , Imageamento por Ressonância Magnética , Masculino , Síndrome
7.
J Neuroradiol ; 35(4): 210-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18242706

RESUMO

There is currently no evidence that treatment of unruptured aneurysms is beneficial. Confronted with the uncertainty, many clinicians are attracted by an individual calculus of risks using numbers extracted from subgroup statistics of observational studies or natural history data. The so-called natural history of unruptured aneurysms refers to a purely man-made ratio of events divided by the number of untreated patients identified by imaging, a ratio heavily influenced by referral patterns and arbitrary clinical decisions. Available studies lacked prespecified hypotheses, exposing all analyses to sampling error and bias, and sample sizes were too small to provide reliable subgroup statistics. Far from being "natural kinds" of aneurysms, subgroups were post-hoc creations. Resulting data-driven statistics can only be exploratory, the error too uncontrollable to serve for clinical decisions. A randomized trial is in order, but selection according to fixed size criteria is ill-advised, given the imprecision of imaging, the influence of other factors such as location, previous history, multiplicity of lesions, risks of treatment, age and the danger of arbitrarily excluding from a long trial a large segment of the population with aneurysms for whom the research question is most pertinent.


Assuntos
Aneurisma Intracraniano/terapia , Diagnóstico por Imagem , Humanos , Aneurisma Intracraniano/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Medição de Risco , Estatística como Assunto
8.
AJNR Am J Neuroradiol ; 28(3): 524-7, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17353328

RESUMO

BACKGROUND AND PURPOSE: Several angiographic features of brain arteriovenous malformations (BAVMs) have been associated with an increased risk of hemorrhage. However, interpretation of these features may not be consistent between observers. We conducted a study to determine inter- and intraobserver agreement of various angioarchitectural characteristics of BAVM. MATERIALS AND METHODS: Two experienced interventional neuroradiologists independently reviewed pre- and post-endovascular treatment angiograms from 50 consecutive patients. Axial CT and/or MR images before treatment were included. We collected the following data: Spetzler-Martin grades, number of involved arterial territories, associated aneurysms by location (circle of Willis, feeding artery, intranidal, and venous), and nidus reduction after endovascular treatment (<33%, 33%-66%, and >66%). The reviewers were compared with each other, and 1 was compared with himself after a 3-month interval. Measures of agreement were performed by using the kappa statistic (kappa) for nominal data and the weighted kappa for ordinal data. RESULTS: Inter- and intraobserver agreement were higher for assessment of the Spetzler-Martin grade (weighted kappa = 0.70/0.75) and nidus size reduction after endovascular treatment (kappa = 0.74/0.77). Inter- and intraobserver agreement were inferior for findings concerning feeding artery aneurysms (kappa = 0.19/0.36), intranidal aneurysms (kappa = 0.34/0.35), and venous aneurysms (kappa = 0.50/0.67). CONCLUSION: Angiographic characteristics of BAVMs considered as risk factors for hemorrhage, such as aneurysms, are not reliably detected on global angiograms between different observers. In contrast, the Spetzler-Martin grading system and angiographic results of endovascular treatment can be used with high observer agreement.


Assuntos
Angiografia Cerebral/estatística & dados numéricos , Embolização Terapêutica , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/terapia , Índice de Gravidade de Doença , Adulto , Angiografia Cerebral/normas , Estudos de Coortes , Humanos , Malformações Arteriovenosas Intracranianas/epidemiologia , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
9.
Diagn Interv Imaging ; 98(3): 227-233, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27473190

RESUMO

PURPOSE: The goal of this study was to estimate the frequency and the quality of agreement studies published in diagnostic imaging journals. MATERIALS AND METHODS: All studies published between January 2011 and December 2012 in four radiology journals were reviewed. Four trained readers evaluated agreement studies using a 24-item form that included the 15 items of the Guidelines for Reporting Reliability and Agreement Studies criteria. RESULTS: Of 2229 source titles, 280 studies (13%) reported agreement. The mean number of patients per study was 81±99 (SD) (range, 0-180). Justification for sample size was found in 9 studies (3%). The number of raters was≤2 in 226 studies (81%). No intra-observer study was performed in 212 (76%) articles. Confidence intervals and interpretation of statistical estimates were provided in 98 (35%) and 147 (53%) of the studies, respectively. In 168 studies (60%), the agreement study was not mentioned in the discussion section. In 8 studies (3%), reporting of the agreement study was judged to be adequate. Twenty studies (7%) were dedicated to agreement. CONCLUSION: Agreement studies are preliminary and not adequately reported. Studies dedicated to agreement are infrequent. They are research opportunities that should be promoted.


Assuntos
Consenso , Variações Dependentes do Observador , Radiografia , Projetos de Pesquisa , Humanos
10.
AJNR Am J Neuroradiol ; 38(3): 432-441, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28082261

RESUMO

BACKGROUND AND PURPOSE: Some patients are at high risk of aneurysm recurrence after endovascular treatment: patients with large aneurysms (Patients Prone to Recurrence After Endovascular Treatment PRET-1) or with aneurysms that have previously recurred after coiling (PRET-2). We aimed to establish whether the use of hydrogel coils improved efficacy outcomes compared with bare platinum coils. MATERIALS AND METHODS: PRET was an investigator-led, pragmatic, multicenter, parallel, randomized (1:1) trial. Randomized allocation was performed separately for patients in PRET-1 and PRET-2, by using a Web-based platform ensuring concealed allocation. The primary outcome was a composite of a residual/recurrent aneurysm, adjudicated by a blinded core laboratory, or retreatment, intracranial bleeding, or mass effect during the 18-month follow-up. Secondary outcomes included adverse events, mortality, and morbidity (mRS > 2). The hypothesis was that hydrogel would decrease the primary outcome from 50% to 30% at 18 months, necessitating 125 patients per group (500 for PRET-1 and PRET-2). RESULTS: The trial was stopped once 250 patients in PRET-1 and 197 in PRET-2 had been recruited because of slow accrual. A poor primary outcome occurred in 44.4% (95% CI, 35.5%-53.2%) of those in PRET-1 allocated to platinum compared with 52.5% (95% CI, 43.4%-61.6%) of patients allocated to hydrogel (OR, 1.387; 95% CI, 0.838-2.295; P = .20) and in 49.0% (95% CI, 38.8%-59.1%) in PRET-2 allocated to platinum compared with 42.1% (95% CI, 32.0%-52.2%) allocated to hydrogel (OR, 0.959; 95% CI, 0.428-1.342; P = .34). Adverse events and morbidity were similar. There were 3.6% deaths (1.4% platinum, 5.9% hydrogel; P = .011). CONCLUSIONS: Coiling of large and recurrent aneurysms is safe but often poorly effective according to angiographic results. Hydrogel coiling was not shown to be better than platinum.


Assuntos
Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/instrumentação , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapêutico , Aneurisma Intracraniano/cirurgia , Adulto , Idoso , Aneurisma Roto/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Platina , Recidiva , Retratamento , Resultado do Tratamento
11.
Biochim Biophys Acta ; 692(2): 296-304, 1982 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-6293563

RESUMO

Studies on (Na+ +K+)-ATPase generally employ detergents such as SDS and deoxycholate. Under such conditions, the purified enzyme possesses high specific activity. The (Na+ +K+)-ATPase from kidney membranes was unmasked by deoxycholate and SDS as described by Jlrgensen and its kinetic properties were studied. The results suggest that these detergents induce some irreversible alterations in the kinetic properties of the native enzyme. Another detergent, saponin, unmasked the (Na+ +K+)-ATPase as effectively as did SDS, but it seems to affect the kinetic properties of the native enzyme to a lesser extent.


Assuntos
Detergentes/farmacologia , Medula Renal/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Tensoativos/farmacologia , Animais , Membrana Celular/enzimologia , Ácido Desoxicólico/farmacologia , Cinética , Ouabaína/metabolismo , Fosfatos/farmacologia , Fosforilação , Potássio/farmacologia , Saponinas/farmacologia , Dodecilsulfato de Sódio/farmacologia
12.
J Am Coll Cardiol ; 26(3): 787-92, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7642874

RESUMO

OBJECTIVES: The arrhythmogenic and electrophysiologic properties of sotalol, a class III antiarrhythmic drug, administered alone and in combination with mexiletine, a class I antiarrhythmic drug, were compared in conscious dogs predisposed to torsade de pointes arrhythmias. BACKGROUND: The utility of sotalol is limited by proarrhythmia related to excessive delays in repolarization. The addition of mexiletine may limit the risk of torsade de pointes because it reduced in vitro the sotalol-induced increase in action potential duration. METHODS: Two studies were performed in eight hypokalemic dogs (plasma potassium level < or = 3.2 mmol/liter) with chronic atrioventricular block (mean ventricular cycle length, RR 1,100 ms) at 3-day intervals using a crossover protocol. Intravenous sotalol (4.5 + 1.5 mg/kg body weight per h) alone was given for 2 h, or, on another day, an intravenous mexiletine infusion (4.5 + 1.5 mg/kg per h) was begun 30 min before sotalol infusion. Spontaneous ventricular cycle length and QT interval and ventricular effective refractory period at the 1,000-ms pacing cycle length were measured at baseline and 30 min after the onset of each drug infusion. The electrocardiogram (ECG) was continuously monitored for torsade de pointes. RESULTS: Sotalol plus mexiletine and sotalol alone had a significant (p < or = 0.05) and similar effect on ventricular cycle length (+ 800 +/- 93 vs. + 690 +/- 104 ms [mean +/- SEM]) and ventricular effective refractory period (+ 20 +/- 4 vs. + 25 +/- 4 ms), but sotalol plus mexiletine had a lesser effect on QT interval (+ 20 +/- 6 vs. + 50 +/- 8 ms, p < or = 0.05). Torsade de pointes is less frequent (one of eight dogs vs. six of eight dogs, p = 0.02) with sotalol plus mexiletine than with sotalol alone. CONCLUSIONS: The coadministration of a class Ib agent can reduce the proarrhythmic potential of a class III drug in experimental animals predisposed to torsade de pointes arrhythmias and further suggests the clinical utility of such a strategy.


Assuntos
Modelos Animais de Doenças , Eletrocardiografia/efeitos dos fármacos , Mexiletina/uso terapêutico , Sotalol/antagonistas & inibidores , Sotalol/uso terapêutico , Torsades de Pointes/tratamento farmacológico , Análise de Variância , Animais , Cães , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Quimioterapia Combinada , Eletrocardiografia/métodos , Eletrofisiologia , Torsades de Pointes/fisiopatologia
13.
AJNR Am J Neuroradiol ; 36(1): 24-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25059693

RESUMO

BACKGROUND AND PURPOSE: The repeatability of head CT interpretations may be studied in different contexts: in peer-review quality assurance interventions or in interobserver agreement studies. We assessed the agreement between double-blind reports of outpatient CT scans in a routine academic practice. MATERIALS AND METHODS: Outpatient head CT scans (119 patients) were randomly selected to be read twice in a blinded fashion by 8 neuroradiologists practicing in an academic institution during 1 year. Nonstandardized reports were analyzed to extract 4 items (answer to the clinical question, major findings, incidental findings, recommendations for further investigations) from each report, to identify agreement or discrepancies (classified as class 2 [mentioned or not mentioned or contradictions between reports], class 1 [mentioned in both reports but diverging in location or severity], 0 [concordant], or not applicable), according to a standardized data-extraction form. Agreement regarding the presence or absence of clinically significant or incidental findings was studied with κ statistics. RESULTS: The interobserver agreement regarding head CT studies with positive and negative results for clinically pertinent findings was 0.86 (0.77-0.95), but concordance was only 75.6% (67.2%-82.5%). Class 2 discrepancy was found in 15.1%; class 1 discrepancy, in 9.2% of cases. The κ value for reporting incidental findings was 0.59 (0.45-0.74), with class 2 discrepancy in 29.4% of cases. Most discrepancies did not impact the clinical management of patients. CONCLUSIONS: Discrepancies in double-blind interpretations of head CT examinations were more common than reported in peer-review quality assurance programs.


Assuntos
Encefalopatias/diagnóstico por imagem , Neurologia/normas , Adulto , Idoso , Método Duplo-Cego , Feminino , Cabeça , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Pacientes Ambulatoriais , Médicos , Tomografia Computadorizada por Raios X/métodos
14.
Biochimie ; 65(8-9): 519-27, 1983.
Artigo em Francês | MEDLINE | ID: mdl-6315083

RESUMO

Incubation of membrane fragments from sheep kidney outer medulla in detergents such as SDS or saponin revealed increased specific (NA+) ATPase activity. Measurement of enzyme phosphorylation from [gamma 32P] ATP showed irreversible alteration of EP to (Na+) ATPase activity ratio when SDS is used as unmasking agent. These results were found with unmasked and purified enzyme.


Assuntos
Rim/enzimologia , Saponinas , Dodecilsulfato de Sódio , ATPase Trocadora de Sódio-Potássio/isolamento & purificação , Trifosfato de Adenosina/metabolismo , Animais , Membrana Celular/enzimologia , Técnicas In Vitro , Ouabaína/farmacologia , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação , Ovinos , ATPase Trocadora de Sódio-Potássio/metabolismo
15.
J Pharmacol Toxicol Methods ; 29(1): 45-57, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8481561

RESUMO

The canine model of ventricular tachycardias (VT) induced by programmed stimulation is used routinely in several laboratories to test antiarrhythmic drugs. The aim of the present study was to determine the rate of success and reproducibility of this model. We analyzed a group of 58 dogs that underwent a 2-hr occlusion and were submitted to programmed electrical stimulation at least 4 days after the surgery. Only 29 dogs (50%) were inducible and included in the study, as 22 dogs died following myocardial infarction, and seven dogs were never inducible. Out of 130 trials, 92 (70%) performed on inducible dogs were positive with 11% of nonsustained ventricular tachycardias, 63% of sustained monomorphic ventricular tachycardias, and 26% of ventricular fibrillation. Inducibility decreased over time in a subgroup of 19 dogs that was submitted to four trials during the first month after the infarction (68% of inducible dogs versus 46% in trials 1 and 4, respectively). Ventricular effective refractory period decreased significantly from 146 +/- 7 msec at trial 1 to 114 +/- 6 msec at trial 4, and the severity of the induced ventricular tachycardias increased. This variability should be considered when planning studies on antiarrhythmic drugs in this model.


Assuntos
Modelos Animais de Doenças , Estimulação Elétrica , Taquicardia Ventricular/fisiopatologia , Animais , Antiarrítmicos/farmacologia , Cães , Eletrofisiologia , Feminino , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Reprodutibilidade dos Testes , Taquicardia Ventricular/tratamento farmacológico , Fatores de Tempo
16.
Fundam Clin Pharmacol ; 9(3): 240-7, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7557819

RESUMO

The proarrhythmic effects of 3-hydroxy-hydroquinidine (3-OH-HQ) and quinidine were compared in a canine model of QT-dependent ventricular arrhythmias. Eight hypokalemic ([K+] < or = 3.2 mmol/l) dogs with AV block (around 45 bpm) were given either drug in a randomized order at 2-day intervals. Each drug was given as two 1 hour doses, with a bolus (low dose: 5 mg/kg or high dose: 10 mg/kg) plus infusion (25 or 50 micrograms/kg/min) protocol. Propranolol infusion was combined with a third hour of the high dose infusion. Electrophysiologic measurements were performed at baseline and 30 minutes after the beginning of each dose and propranolol infusion, and proarrhythmic events were recorded 30 minutes before and during the experiment. Neither drugs altered the ventricular cycle length. Quinidine and 3-OH-HQ prolonged the QT interval similarly and significantly when paced at 60 bpm after the low dose (+39 +/- 18 and +28 +/- 22 msec, respectively) and after the high dose (+51 +/- 29 and +50 +/- 22 msec). Quinidine was more arrhythmogenic than 3-OH-HQ: 7/8 dogs (p < or = 0.05) developed ventricular arrhythmias (isolated, repetitive ventricular beats, or polymorphic ventricular tachycardias) during quinidine infusion (low dose: 4 dogs) compared to 3/8 dogs (NS) during 3-OH-HQ infusion (low dose: 1 dog). Addition of propranolol-induced bradycardia (around 30 bpm) caused torsades de pointes (wave burst arrhythmias) or polymorphic ventricular tachycardias after both drugs (in 3 dogs after quinidine and in 2 dogs after 3-OH-HQ). Thus 3-OH-HQ was slightly less arrhythmogenic than quinidine in this model of torsades de pointes, but the addition of an extra favouring factor (bradycardia) reduced that difference.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Quinidina/análogos & derivados , Antagonistas Adrenérgicos beta/farmacologia , Animais , Arritmias Cardíacas/fisiopatologia , Complexos Cardíacos Prematuros/induzido quimicamente , Complexos Cardíacos Prematuros/fisiopatologia , Cães , Eletrocardiografia/efeitos dos fármacos , Eletrofisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Propranolol/farmacologia , Quinidina/antagonistas & inibidores , Quinidina/toxicidade , Taquicardia Ventricular/fisiopatologia
17.
Pathol Res Pract ; 178(1): 40-7, 1983 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6227872

RESUMO

The ameloblastic fibrosarcoma is a rare variety of neoplasm. Three new cases reported here occurred within preexistent benign odontogenic tumors (ameloblastic fibroma or fibro-odontoma). These large, osteolytic tumors, spreading to adjacent soft parts, recurred after surgical treatment in two cases. One of them had a lethal course, with pleuro-pulmonary, mediastinal lymph node and hepatic metastases. Histologically, these sarcomas show a malignant mesenchymal component and few benign ameloblastic islands, which often disappear after one or several recurrences. Histoenzymologically, a high level of alkaline phosphatase and ATPase activities is always present, a feature not present in common fibrosarcomas. The ultrastructural study demonstrates, in analogy with odontogenic myxomas, clear cells provided with numerous microfilaments, secretory cells and also some fibroblasts and myofibroblast-like cells. In addition to these pleomorphic cells, a great number of peculiar granular cells with numerous lysosomal bodies were also found. The histogenesis of these tumors in unknown. Perhaps the epithelial component, being unable to assume its functions of organization, may initiate the malignant transformation of its odontogenic mesenchyme.


Assuntos
Neoplasias Maxilomandibulares/patologia , Tumores Odontogênicos/patologia , Fosfatase Ácida/análise , Adenosina Trifosfatases/análise , Adulto , Fosfatase Alcalina/análise , Criança , Histocitoquímica , Humanos , Neoplasias Maxilomandibulares/ultraestrutura , Masculino , Microscopia Eletrônica , Tumores Odontogênicos/ultraestrutura
18.
Int J Oral Maxillofac Surg ; 32(2): 132-6, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12729771

RESUMO

This study evaluated the treatment of intraosseous vascular malformation of the mandible. We analysed the medical records of 12 patients treated at the Salpêtrière Hospital (Paris, France) for vascular malformation of the mandible between 1965 and 1996. There were six male and six female patients, with a mean age of 16 years. The mean follow-up time was ten years. The treatment was surgery (enucleation or resection) or interventional radiology (arterial embolization or transosseous transcutaneous embolization). There are several indications for treatment, including age, and the size and type of vascular malformation (active or passive).


Assuntos
Malformações Arteriovenosas/cirurgia , Mandíbula/irrigação sanguínea , Adolescente , Adulto , Fatores Etários , Malformações Arteriovenosas/classificação , Criança , Pré-Escolar , Embolização Terapêutica/métodos , Feminino , Seguimentos , Hemangioma Cavernoso/cirurgia , Humanos , Masculino , Neoplasias Mandibulares/cirurgia , Pessoa de Meia-Idade , Radiologia Intervencionista , Estudos Retrospectivos , Resultado do Tratamento
19.
Int J Oral Maxillofac Surg ; 17(4): 219-23, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3139789

RESUMO

The 3 cases of cherubism reported affected the mandible. They were all studied by means of histo-enzymological and ultrastructural methods. This study demonstrated 3 stages in the morphological evolution of the disease, corroborated by clinical data. The 1st stage was characterized by an osteolytic granuloma with round, fusiform and giant-cells and a high level of activity of acid phosphatase. The 2nd stage showed repair with proliferation of highly active fibroblasts (increase in activity of leucine aminopeptidase). The 3rd stage exhibited an osteogenesis with high activity of alkaline phosphatase and ATPase. The pathogenesis of this rare osteodysplasia is discussed.


Assuntos
Querubismo/patologia , Mandíbula/patologia , Adolescente , Adulto , Querubismo/enzimologia , Fibroblastos/enzimologia , Fibroblastos/patologia , Granuloma/patologia , Humanos , Masculino , Mandíbula/enzimologia , Mandíbula/ultraestrutura , Microscopia Eletrônica , Osteoblastos/ultraestrutura , Osteólise/patologia , Oxirredutases/metabolismo
20.
Int J Oral Maxillofac Surg ; 30(4): 291-5, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11518350

RESUMO

A prospective study was carried out involving patients presenting with facial fractures sustained during sports. One hundred and forty patients were admitted to the Pitié-Salpêtrière University Hospital of Paris between March 1998 and March 2000, accounting for 13.3% of all patients with facial bone fractures. The ratio of males to females was 7.2:1 and the mean age was 28.5 years. The majority of accidents occurred during soccer (25.0%), followed by rugby (15.0%), and as a consequence of collisions between players (50.7%). The majority of the injuries involved the mandible (34.4%), the zygomatic bone (23.4%) and the nasal bone (15.6%). The sporting activities were classified as either contact or non-contact sports. Frontal sinus, central midface and LeFort fractures were seen more often in vehicular sports such as mountainbiking and skiing. The authors stress the importance of preventive measures, including the use of protective equipment, periodic sports medical check-ups and personal discipline.


Assuntos
Traumatismos em Atletas/epidemiologia , Traumatismos Maxilofaciais/epidemiologia , Traumatismos Maxilofaciais/etiologia , Fraturas Cranianas/epidemiologia , Fraturas Cranianas/etiologia , Adulto , Ciclismo/lesões , Feminino , Futebol Americano/lesões , França/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Futebol/lesões
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