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Biomedical subjects

K Szabo

Publications and source records attributed to K Szabo.

At least 19 recordsLinked to original sources
PubMed2003

Effect of incomplete (spontaneous and postthrombolytic) recanalization after middle cerebral artery occlusion: a magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Early reperfusion is one of the best predictors of good outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this study was to analyze the frequency and relevance of incomplete recanalization for tissue and clinical outcome. METHODS: From a larger acute stroke database (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem occlusion (excluding carotid T-occlusions) were selected. These patients had received a multiparametric stroke MRI protocol including diffusion- and perfusion-weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom onset, at day 1 and after 1 week. Recanalization status was determined with MRA on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and used to group patients into those with persistent occlusion (0) or minimal (1), partial (2), or complete (3) recanalization. RESULTS: Incomplete recanalization according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2: n=19), complete recanalization in 10, and persistent occlusion in 33. There was no statistically significant difference in any of the clinical (National Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion, PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller in patients with recanalization (even in patients with only minimal recanalization) and outcome was related to the degree of recanalization (mean modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with no, minimal, partial, and complete recanalization, respectively). Both incomplete and complete recanalization was more frequent in patients receiving thrombolysis. CONCLUSIONS: Incomplete recanalization on day 1 is a frequent MR finding after MCA main stem occlusion, indicating a more favorable clinical course than persistent occlusion. MR indicators of early recanalization could be useful surrogates of efficacy in thrombolytic trials.

Adult↗
PubMed2003

Bilateral internal carotid artery dissection mimicking inflammatory demyelinating disease.

BACKGROUND AND PURPOSE: Internal carotid artery (ICA) dissection (ICAD) may be extremely difficult to diagnose only on the basis of historical information and clinical signs, and even standard brain imaging (computed tomography [CT], T2-weighted magnetic resonance imaging [MRI]) may not be sufficient to delineate the underlying pathology clearly, as shown in this case. METHODS: The clinical presentation and parenchymal lesion pattern on CT were suggestive of inflammatory demyelinating disease, and additional multiparametric MRI was performed. RESULTS: Diffusion-weighted MRI, magnetic resonance angiography, and perfusion-weighted MRI revealed acute ischemic lesions, bilateral ICA obstruction, and bilateral hypoperfusion in the middle cerebral artery territories. Bilateral ICAD was confirmed by Doppler and duplex ultrasound, and anticoagulation therapy was initiated. A follow-up examination showed recanalization of the obstructed ICAs and the normalization of cerebral perfusion. CONCLUSION: This case illustrates the importance of demonstrating the pathology and the value of multiparametric MRI techniques for the diagnosis and monitoring of ICAD and its hemodynamic consequences.

Carotid Artery, Internal, Dissection↗
PubMed2002

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Acute Disease↗
PubMed2001

A diffusion-weighted MRI study of acute ischemic distal arm paresis.

OBJECTIVE: To study the site of the ischemic lesion, the underlying cause, and the prognosis of acute stroke with distal arm paresis. METHOD: The authors investigated 14 consecutive patients with acute distal arm paresis with a diagnostic stroke protocol and early MRI, including T2-weighted images, diffusion-weighted images (DWI), and perfusion-weighted images (PWI). Acute DWI lesions were shown on coregistered T2-weighted images for analysis of the exact anatomic lesion location. RESULTS: Patients showed a uniform (7/14), radial (3/14), or ulnar (4/14) distribution of hand paresis. In all cases, DWI identified small lesions located in the motor cortex. Topographic lesion analysis, which was correlated with the clinical deficit, showed lesions centered in the hand knob area (2/14), involving the lateral (6/14), medial (4/14), or both (2/14) borders of the hand knob. PWI (calculated time-to-peak maps) did not show a mismatch between the DWI lesion and the PWI lesion. In six patients, DWI and PWI lesions were identical in size and location; no definite perfusion deficit was seen in eight patients. In agreement with PWI, no patient showed clinical worsening, and six patients recovered completely within a week. Further investigations showed a potential source of embolus in 11 cases. CONCLUSIONS: Acute ischemic distal arm paresis is usually caused by a small cortical lesion in the motor hand cortex attributable to distal Rolandic artery obstruction without additional tissue at risk. These findings confirm the observed benign clinical course and its apparent main cause (artery-to-artery or cardiac embolism).

Acute Disease↗
PubMed2001

The possible association of in vivo leukocyte-platelet heterophilic aggregate formation and the development of diabetic angiopathy.

Circulating leukocyte-platelet heterophilic aggregates produce procoagulant, oxidative and mitogenic substances, and can cause microembolism in capillaries as well as acute arterial thrombosis. Our aim was to determine if there was any difference in the number of circulating heterophilic aggregates between diabetic patients and controls, if the formation of aggregates correlated with the actual HgbA1c level, duration of diabetes and postprandial rise in serum glucose level, with different vascular complications and whether decreasing postprandial serum glucose had any effect on heterophilic aggregate formation. The number of circulating heterophilic aggregates was measured in 90 diabetic patients (Type 1, 29; Type 2, 61) and in 23 control subjects by a flow-cytometric assay, and the result was given as percentage of the respective leukocyte subsets. There was no significant difference in lymphocyte-platelet and neutrophil-platelet aggregate number in patients and controls; however, there was a significant difference in the percentage of monocyte-platelet aggregates between the diabetic and control group (Type 1, 43.0 +/- 17.8; Type 2, 34.9 +/- 12.5; control, 24.6 +/- 8.2; P < 0.01 and P < 0.5, respectively). Patients with proliferative retinopathy and nephropathy showed the highest number of monocyte-platelet aggregates. No significant correlation was, however, found with HgbA1c. In Type 2 diabetes a non-significant, but remarkable, tendency between elevation of postprandial serum glucose levels and platelet-monocyte aggregate formation was observed and acarbose seemed to be effective in decreasing both. This study provides further support that heterophilic aggregates might have role in the pathogenesis of diabetic vascular complications.

Acarbose↗
PubMed2001

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗
PubMed2000

MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping.

The human MDR3 gene is a member of the multidrug resistance (MDR) gene family. The MDR3 P-glycoprotein is a transmembrane protein that translocates phosphatidylcholine. The MDR1 P-glycoprotein related transports cytotoxic drugs. Its overexpression can make cells resistant to a variety of drugs. Attempts to show that MDR3 P-glycoprotein can cause MDR have been unsuccessful thus far. Here, we report an increased directional transport of several MDR1 P-glycoprotein substrates, such as digoxin, paclitaxel, and vinblastine, through polarized monolayers of MDR3-transfected cells. Transport of other good MDR1 P-glycoprotein substrates, including cyclosporin A and dexamethasone, was not detectably increased. MDR3 P-glycoprotein-dependent transport of a short-chain phosphatidylcholine analog and drugs was inhibited by several MDR reversal agents and other drugs, indicating an interaction between these compounds and MDR3 P-gp. Insect cell membranes from Sf9 cells overexpressing MDR3 showed specific MgATP binding and a vanadate-dependent, N-ethylmaleimide-sensitive nucleotide trapping activity, visualized by covalent binding with [alpha-(32)P]8-azido-ATP. Nucleotide trapping was (nearly) abolished by paclitaxel, vinblastine, and the MDR reversal agents verapamil, cyclosporin A, and PSC 833. We conclude that MDR3 P-glycoprotein can bind and transport a subset of MDR1 P-glycoprotein substrates. The rate of MDR3 P-glycoprotein-mediated transport is low for most drugs, explaining why this protein is not detectably involved in multidrug resistance. It remains possible, however, that drug binding to MDR3 P-glycoprotein could adversely affect phospholipid or toxin secretion under conditions of stress (e.g. in pregnant heterozygotes with one MDR3 null allele).

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

The level of C/EBP protein is critical for cell migration during Drosophila oogenesis and is tightly controlled by regulated degradation.

The C/EBP transcription factor, Slbo, is required for migration of border cells during Drosophila oogenesis. Unexpectedly, we find that neither increase nor decrease of Slbo activity is tolerated in border cells. Correct protein level is in part ensured by cell type-specific regulated turnover of Slbo protein. Through genetic screening, we identify two genes that are involved in this regulation. The Ubp64 ubiquitin hydrolase acts as a stabilizer of Slbo protein. A novel gene, tribbles, is a negative regulator of slbo in vivo. Tribbles acts by specifically targeting Slbo for rapid degradation via ubiquitination.

Animals↗
PubMed2000

Increased leukocyte-platelet adhesion in chronic myeloproliferative disorders with high platelet counts.

The heterophilic adhesions between monocytes and platelets may result in the modification of both platelet and monocyte function. This mutual modification includes a greater activation of platelets with increased production of PDGF and other metabolites as well as an enhanced tissue factor expression of monocytes with greater activity in the circulation. The heterophilic aggregation has been well documented during extracorporal circulation, haemodialysis and in diabetic retinopathy. Here we provide evidence that there is significant increase of monocyte-platelet aggregates in disorders associated with high platelet counts, such as chronic myeloproliferative disorders. The presence of these heterophilic aggregates may contribute to the vascular complications observed frequently in polycythaemia vera and essential thrombocythaemia.

Adult↗
PubMed2000

Failure to demonstrate peri-infarct depolarizations by repetitive MR diffusion imaging in acute human stroke.

BACKGROUND AND PURPOSE: Peri-infarct depolarizations (PIDs) have been demonstrated with diffusion-weighted MRI (DWI) in experimental stroke and are regarded as an important mechanism of ischemic injury. We tested the hypothesis that PIDs are of relevance for the early enlargement of human brain infarcts. METHODS: Ten stroke patients were investigated by repetitive imaging of the apparent diffusion coefficient (ADC) in the acute phase (7 patients) or subacute phase (3 patients) of developing cortical infarction. In each patient, 20 ADC maps were obtained from serially measured echo-planar DWI (interval of 45 seconds). Data analysis focused on the potential spatial and temporal ADC changes, including structured qualitative analysis, calculation of subtraction images, serial analysis of regions of interest positioned in the infarct core and border, and calculation of hemispheric lesion areas, depending on various ADC thresholds ranging between 0 and 800 microm(2)/s. RESULTS: Data analysis was unable to disclose any time-dependent changes in ADC that would resemble PID. In ischemic regions, the ADC reduction significantly progressed from the infarct border (555+/-96 microm(2)/s) to the infarct core (431+/-104 microm(2)/s, P:<0.01). CONCLUSIONS: By using an MRI protocol with high temporal resolution and elaborated postprocessing, we were unable to demonstrate a pattern of diffusion changes that would be indicative of PID in human stroke. Experimental infarction and human stroke may differ in the detectability of PID.

Acute Disease↗
PubMed1999

The microangioarchitecture of the conducting system in cattle.

Macroscopic researches on heart vascularization have indicated that the angioarchitecture of the conducting system differs from that of the normal myocardium. In order to observe this variance, eight cow hearts were dissected for perfusion through the Ramus ventricularis dexter and Ramus septalis of the A. coronaria dextra with Ringer's solution, and then injected with Mercox. After corrosion in KOH the casts were prepared for observation in a SEM. In the region of the sinoatrial node no special capillary arrangement was observed, but only valves on the venous side. At the atrioventricular node and the bundle of His, the arterioles showed a diffuse formation, filling this area with a regular caliber, without any special capillary orientation. The arteries that reach the right bundle dichotomized and ran collateral to the opposite extremity of this structure, lying parallel. The vessels with the biggest caliber were deeply positioned. In the left bundle the arterioles showed a net like figure, mainly in one plane. Following the form of the bundle, and below the conducting tissue a big anastomotic venous arrangement is observable.

Animals↗
PubMed1999

Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand.

The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](-)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (f(max)), its retention value at 75 minutes (fT), and its normalized retention (f(rel) = fT/f(max)) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DV(T)) and its specific binding component (DV(S)). Both the noncompartmental (fT,f(rel)) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](-)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter f(rel) demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, f(rel) demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform lnDV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental f(rel) with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters (k1, k2, and BV), and that both the noncompartmental parameter f(rel) and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted.

Adult↗