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1.
J Neuroimaging ; 32(1): 97-103, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34591348

RESUMO

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right-to-left-shunt underlies interindividual variability. Here, we aimed to assess whether a pressure-controlled standardization of VM is useful to estimate PFO size. METHODS: We included patients aged 18-80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE-based PFO size. The predictive value of TCD at rest and VM-based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross-tab-analyses. RESULTS: We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22-80]) with PFO were included. We found an association between MES count and expiratory pressure (p < .001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. CONCLUSION: Our data provide evidence that TCD with step-wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed.


Assuntos
Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Transesofagiana/métodos , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/métodos , Manobra de Valsalva , Adulto Jovem
3.
Sci Rep ; 10(1): 19568, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177570

RESUMO

The profiles of time-contrast (TC) -curves from popular MRI injectors derived at the injection site of the attached tube-line system were compared. Variations of TC-profiles were previously reported to potentially influence image quality in time critical MRI measurements. TC-curves from five injectors obtained during commonly used injection protocols were assessed according to representative quality criteria: (1) correlation strength between a fitted boxcar function and the TC-curve (cBCF) and (2) difference between true and expected injection time (dBIT). Additionally, the impact from technical injector properties: pump type, line volume, maximum injection power and type of contrast medium (CM) on the TC-profiles was evaluated. Injectors using a piston-syrinx (PS) mechanism for CM-injection performed significantly better than those working with a peristaltic roller pump (RP) technique. Besides injection mechanism, line filling volume showed a strong influence on the final TC-curves, where larger filling volumes induced worse cBCF- and dBIT-results. Therefore, to achieve an optimal bolus in clinical MRI use of a PS-injector seems recommendable. Besides their pump mechanism, RP-injectors appeared additionally hampered by their high volume line systems, pointing out an unfavourable coinicidence of these technical features in RP-injectors. This should be considered, particularly, in comparative or time-critical MRI-studies.

4.
Neurology ; 93(9): e895-e907, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31391248

RESUMO

OBJECTIVE: To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). METHODS: We applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA. RESULTS: Quantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. CONCLUSIONS: Our findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Atrofia Muscular Espinal/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
5.
Front Physiol ; 9: 1945, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30697166

RESUMO

Purpose: Perfusion magnetic resonance imaging (P-MRI) is part of the mismatch concept employed for therapy decisions in acute ischemic stroke. Using dynamic susceptibility contrast (DSC) MRI the time-to-maximum (Tmax) parameter is quite popular, but its inconsistently defined computation, arterial input function (AIF) selection, and the applied deconvolution method may introduce bias into the assessment. Alternatively, parameter free methods, namely, standardized time-to-peak (stdTTP), zf-score, and standardized-zf (stdZ) are also available, offering consistent calculation procedures without the need of an AIF or deconvolution. Methods: Tmax was compared to stdTTP, zf-, and stdZ to evaluate robustness of infarct volume estimation in 66 patients, using data from two different sites and MR systems (i.e., 1.5T vs. 3T; short TR (= 689 ms) vs. medium TR (= 1,390 ms); bolus dose 0.1 or 0.2 ml/kgBW, respectively). Results: Quality factors (QF) for Tmax were 0.54 ± 0.18 (sensitivity), 0.90 ± 0.06 (specificity), and 0.87 ± 0.05 (accuracy). Though not significantly different, best specificity (0.93 ± 0.05) and accuracy (0.90 ± 0.04) were found for stdTTP with a sensitivity of 0.56 ± 0.17. Other tested parameters performed not significantly worse than Tmax and stdTTP, but absolute values of QFs were slightly lower, except for zf showing the highest sensitivity (0.72 ± 0.16). Accordingly, in ROC-analysis testing the parameter performance to predict the final infarct volume, stdTTP and zf showed the best performance. The odds for stdTTP to obtain the best prediction of the final infarct size, was 6.42 times higher compared to all other parameters (odds-ratio test; p = 2.2*10-16). Conclusion: Based on our results, we suggest to reanalyze data from large cohort studies using the parameters presented here, particularly stdTTP and zf-score, to further increase consistency of perfusion assessment in acute ischemic stroke.

6.
J Neurol ; 262(7): 1698-705, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25957641

RESUMO

The aim of this study was to evaluate associations between co-medications and survival of patients with amyotrophic lateral sclerosis (ALS). Prescription databases of the Austrian sickness funds covering more than 5 million people formed the basis of this study. ALS cases were deduced from riluzole prescriptions during the study period from January 1, 2008, to June 30, 2012. After adjusting for potential confounding factors associations between co-medications and ALS survival were analyzed. A total of 522 ALS patients could be identified during the study period. Sixteen of the most frequently used drug classes were considered for the survival analyses of which two were nominally associated with ALS survival. Proton pump inhibitors (PPI) were negatively correlated with survival (HR 1.34, 95 % CI 1.04-1.73) and centrally acting muscle relaxants (CAMR) showed a positive association (HR 0.56, 95 % CI 0.39-0.81). After correcting for multiple testing, the association between CAMR and ALS survival remained significant (p = 0.03). In conclusion, this is the first study systematically evaluating potential associations between commonly used drugs and ALS disease course. We report a positive association between CAMR use and survival, which may have derived from an indication bias representing the better prognosis of the upper motor neuron predominant disease variant. However, this is still interesting since it demonstrates the sensitivity of our study design to pick up survival effects. The use of large prescription registries could thus provide a valuable basis to find clues to underlying pathophysiological mechanisms in ALS.


Assuntos
Esclerose Lateral Amiotrófica , Fármacos Neuroprotetores/uso terapêutico , Riluzol/uso terapêutico , Idoso , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/mortalidade , Áustria/epidemiologia , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estatísticas não Paramétricas , Análise de Sobrevida
7.
Int J Clin Pharmacol Ther ; 53(1): 54-65, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25500488

RESUMO

INTRODUCTION: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects. MATERIAL AND METHODS: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously. RESULTS: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2. CONCLUSION: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Curcumina/administração & dosagem , Curcumina/farmacocinética , Adolescente , Adulto , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/urina , Biotransformação , Curcumina/efeitos adversos , Curcumina/análogos & derivados , Curcumina/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Feminino , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Lipossomos , Masculino , Pessoa de Meia-Idade , Eliminação Renal , Medição de Risco , Adulto Jovem
8.
Biomed Res Int ; 2014: 458592, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24592391

RESUMO

PURPOSE: Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism. METHODS: In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs) were analyzed over 48 hours. RESULTS: At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism. CONCLUSIONS: Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Saúde , Heme Oxigenase-1/genética , Administração Oral , Adolescente , Adulto , Bilirrubina/sangue , Curcumina/efeitos adversos , Relação Dose-Resposta a Droga , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
9.
Anticancer Res ; 33(9): 3629-34, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24023289

RESUMO

BACKGROUND: The anti-inflammatory and antiproliferative agent curcumin has poor oral bioavailability and solubility in plasma. Liposomal formulations have therefore been developed, but the toxicity of these preparations is not yet established. We investigated the influence of free and liposomally formulated curcumin on human red blood cell (RBC) morphology in vitro. MATERIALS AND METHODS: EDTA-buffered whole blood from two healthy individuals was incubated with different concentrations (1, 10, 100 µg/ml) of free or liposomal curcumin. RBC morphology and mean cellular volume (MCV) were examined at up to 4 hours of incubation. RESULTS: Dose-dependent echinocyte formation was observed after incubation with free, and liposomal curcumin, with a threshold concentration of 10 µg/ml and peak effect after 30 minutes. A concomitant increase in mean cellular volume was detectable. CONCLUSION: Curcumin and liposomal curcumin cause dose-dependent changes in the shape of RBCs. This effect may represent an early sign of dose-limiting toxicity following intravenous administration.


Assuntos
Curcumina/farmacologia , Eritrócitos/efeitos dos fármacos , Lipossomos , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro
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