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2.
Acta Neurochir (Wien) ; 158(11): 2039-2044, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27605230

RESUMO

BACKGROUND: Chronic subdural haematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The recurrence rate of cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclo-oxygenase-2 (COX-2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks' time postoperatively in comparison to a control group. METHOD: The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher's exact test (significance level of alpha, 0.05 [two-sided]). RESULTS: After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers. CONCLUSIONS: The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Idoso , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Pituitary ; 18(5): 613-20, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25492407

RESUMO

PURPOSE: Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. METHODS: 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). RESULTS: 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. CONCLUSION: Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.


Assuntos
Adenoma/cirurgia , Angiografia/métodos , Corantes/administração & dosagem , Hipofisectomia/métodos , Verde de Indocianina/administração & dosagem , Microscopia de Fluorescência , Microscopia de Vídeo , Microcirurgia/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/irrigação sanguínea , Adenoma/complicações , Adenoma/patologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Cuidados Intraoperatórios , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/irrigação sanguínea , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Stroke ; 29(10): 2129-35, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9756594

RESUMO

BACKGROUND AND PURPOSE: Activation of endothelial cells is a consequence of cerebral ischemia and leads to the expression of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, which can be released into the blood. This study aimed to define the kinetics of soluble adhesion molecule serum levels after cerebral ischemia and their correlation with the extent of neurological deficits, clinical outcome, and infarct volume as measured on CT scans. Methods-Plasma levels of soluble (s) ICAM-1, sVCAM-1, and sE-selectin were repeatedly determined by ELISA in 38 patients during a period of 14 days after acute cerebral ischemia. RESULTS: Soluble adhesion molecule levels demonstrated considerable variability. Overall, concentrations revealed characteristic and significant changes after completed strokes but not after transient ischemic attacks. In patients with completed stroke (n=26) but not in patients with transient ischemic attacks (n=12), sICAM-1 peaked within 24 hours (P=0.04), sVCAM-1 reached a maximum after 5 days (P=0.02), and sE-selectin levels decreased after 5 days (P=0.002). There was no clear-cut correlation of soluble adhesion molecule levels with infarct volume or clinical disability. The initial increase of sE-selectin levels was higher in more disabled patients (P=0.02). sICAM-1 levels were higher in patients with signs of infection (n=9; P=0.03). CONCLUSIONS: As a result of large interindividual variability influenced by ischemia-independent factors, soluble adhesion molecules are not reliable candidates as surrogate markers in acute cerebral ischemia. The characteristic profile of individual soluble adhesion molecules after completed stroke supports prior hypotheses of their involvement in the pathogenesis of acute cerebral ischemia, but this needs to be clarified in detail.


Assuntos
Transtornos Cerebrovasculares/sangue , Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Infarto Cerebral/sangue , Infarto Cerebral/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Solubilidade , Fatores de Tempo , Tomografia Computadorizada por Raios X
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