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R Markus

Publications and source records attributed to R Markus.

At least 19 recordsLinked to original sources
PubMed2004

Hypoxic tissue in ischaemic stroke: persistence and clinical consequences of spontaneous survival.

In ischaemic stroke, expansion of the infarct core occurs at the expense of surrounding hypoxic, metabolically compromised tissue over a period of 24 h or more in a considerable proportion of patients. It is uncertain whether hypoxic tissue observed at later times after stroke onset retains the potential for survival or whether such survival has an impact on functional outcome. These factors may determine the effectiveness of therapeutic strategies aimed at salvaging this tissue. We tested the hypotheses that metabolically compromised hypoxic tissue observed within 48 h after onset of ischaemic stroke retains the potential for spontaneous survival and that the impact of such survival on functional outcome is time dependent. Consecutive patients presenting within 48 h of ischaemic stroke were studied with [(18)F]fluoromisonidazole, a ligand binding to hypoxic but viable tissue, and PET. Subjects were grouped into two time epochs, </=12 and >12 h, based on the interval from stroke onset to the time of tracer injection, and had infarct volumes measured on CT/MRI at 7 days (n = 60). The total ischaemic volume (TIV) and the proportion of the TIV that spontaneously survived (surviving hypoxic volume ratio, SHVR) were defined from the co-registered CT/MRI images. These volumetric measures were correlated with neurological outcome assessed at day 7-10 by percentage change in the National Institutes of Health Stroke Scale (DeltaNIHSS), and at 3 months by Barthel Index (BI) and modified Rankin Score (mRS). Of 66 patients investigated, hypoxic tissue occurred in 33 and outcome data was available in 27. Hypoxic tissue constituted >20% of the TIV in 60% of studies </=12 h and 16% >12 h. The spontaneously surviving proportion of the TIV (median 6.9%) or hypoxic tissue (median 45.9%) was not significantly different in patient subgroups studied </=12 or >12 h after stroke onset. Spontaneous survival of hypoxic tissue (surviving hypoxic volume ratio) was associated with improved neurological outcome in both time epochs: </=12 h, DeltaNIHSS (r = 0.85, P < 0.01), day 90 BI (r = 0.86, P < 0.01) and day 90 mRS (r = -0.89, P < 0.01); >12 h, DeltaNIHSS (r = 0.59, P < 0.01) and day 90 mRS (r = -0.46, P < 0.05). The finding that similar proportions of hypoxic tissue survived spontaneously within each time epoch suggests that its fate is not predetermined. The favourable neurological outcome associated with spontaneous survival of hypoxic tissue, even 12-48 h after stroke onset, suggests that the volume of hypoxic tissue that progressed to infarction may represent a valuable target for therapeutic intervention.

Adult↗
PubMed2003

Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke.

BACKGROUND AND PURPOSE: We sought to characterize the spatial and temporal evolution of human cerebral infarction. Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18F-fluoromisonidazole (18F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke. METHODS: Patients with acute middle cerebral artery territory stroke were imaged with 18F-FMISO PET (n=19; <6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (P<0.05; >1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch. RESULTS: Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; P<0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; P<0.05). CONCLUSIONS: These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.

Adult↗
PubMed2002

Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke.

Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.

Acute Disease↗
PubMed2002

Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is the most serious complication of thrombolytic therapy for stroke. We explored factors associated with this complication in the Australian Streptokinase Trial. METHODS: The initial CT scans (< or =4 hours after stroke) of 270 patients were reviewed retrospectively by an expert panel for early signs of ischemia and classified into the following 3 categories: no signs or < or =1/3 or >1/3 of the vascular territory. Hemorrhage on late CT scans was categorized as major or minor on the basis of location and mass effect. Stepwise, backward elimination, multivariate logistic regression analysis was used to identify risk factors for each hemorrhage category. RESULTS: Major hemorrhage occurred in 21% of streptokinase (SK) and 4% of placebo patients. Predictors of major hemorrhage were SK treatment (odds ratio [OR], 6.40; 95% CI, 2.50 to 16.36) and elevated systolic blood pressure before therapy (OR, 1.03; 95% CI, 1.01 to 1.05). Baseline systolic blood pressure >165 mm Hg in SK-treated patients resulted in a >25% risk of major secondary hemorrhage. Early ischemic CT changes, either < or =1/3 or >1/3, were not associated with major hemorrhage (OR, 1.58; 95% CI, 0.65 to 3.83; and OR, 1.11; 95% CI, 0.45 to 2.76, respectively). Minor hemorrhage occurred in 30% of the SK and 26% of the placebo group. Predictors of minor hemorrhage were male sex, severe stroke, early CT changes, and SK treatment. Ninety-one percent of patients with major hemorrhage deteriorated clinically compared with 23% with minor hemorrhage. CONCLUSIONS: SK increased the risk of both minor and major hemorrhage. Major hemorrhage was also more likely in patients with elevated baseline systolic blood pressure. However, early CT changes did not predict major hemorrhage. Results from this study highlight the importance of baseline systolic blood pressure as a potential cause of hemorrhage in patients undergoing thrombolysis.

Acute Disease↗
PubMed2001

CT-guided preoperative needle localization of MRI-detected breast lesions.

To assess the value of accurate preoperative CT-guided needle localization of occult breast lesions, we reviewed a total of 39 needle-directed biopsies of breast tumors in 24 women. The average age was 52.9 years (range 31-67). All lesions were nonpalpable and mammographically, as well as sonographically occult. They were solely seen on MR-images. After demonstrating the suspicious region on CT scans, a hookwire was inserted. The correct position was confirmed by a control scan. The subsequent histopathological examination showed that 28 of the lesions (71.8%) were benign, among them mastopathy, fibrosis, fibroadenoma, papilloma, intramammary lymph node, liponecrosis and epitheliosis. Eleven lesions (28%) were malignant and showed either lobular, ductal or tubular cancer. Our results endorse that CT guided needle localization is a helpful method that allows a precise surgical excision of the suspect area with the removal of a minimal amount of breast tissue.

Adult↗
PubMed2001

The brain decade in debate: IV. Chronobiology.

The present article is the adapted version of an electronic symposium organized by the Brazilian Society of Neuroscience and Behavior (SBNeC) which took place on June 14, 2000. The text is divided into three sections: I. The main issues, II. Chronodrugs, and III. Methods. The first section is dedicated to the perspectives of chronobiology for the next decade, with opinions about the trends of future research being emitted and discussed. The second section deals mostly with drugs acting or potentially acting on the organism's timing systems. In the third section there are considerations about relevant methodological issues concerning data analysis.

Brain↗
PubMed2001

A better potassium hydroxide preparation? In vivo diagnosis of tinea with confocal microscopy.

BACKGROUND: Traditional diagnostic testing for dermatophyte infection currently requires skin scraping for light microscopy and/or fungal culture or skin biopsy. Immunofluorescent microscopy can also be used with calcofluor stain. All of these tests can be time-consuming to perform, require a waiting period for results, and are invasive. We investigated the use of a real-time, noninvasive, confocal microscope in visualizing dermatophyte hyphae in vivo. OBSERVATIONS: Confocal microscopic imaging of active tinea can clearly identify dermatophyte hyphae within the upper epidermis after potassium hydroxide application. The hyphae appear as bright linear branching objects not found in uninvolved skin. CONCLUSIONS: It is possible to immediately and painlessly image dermatophyte hyphae in active lesions of tinea by means of a confocal microscope. With further improvement, imaging devices may be available to physicians to instantly and noninvasively evaluate a variety of skin disorders in microscopic detail.

Adult↗
PubMed2000

The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke.

We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued.

Adult↗
PubMed1993

Treatment of chronic hepatitis B with interferon alpha-2b and interleukin-2.

A total of 37 patients with histologically confirmed chronic viral hepatitis B and presence of HBV-DNA and HBsAg in the serum were treated in a randomized, prospectively controlled multicenter trial either with recombinant IFN alpha-2b alone or a combination of IFN alpha-2b and recombinant IL-2. Twenty-two patients from group A were treated with 3 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Starting at month 2 IL-2 was added: priming doses of 1.5 million CU were given s.c. on the first 2 days of each of the remaining 3 months, followed by maintenance doses of 0.3 million CU daily for 5 days per week. Fifteen patients from group B received 5 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Five patients from group A (24%) and 4 patients from group B (28%) cleared HBV-DNA and HBeAg from the serum, and normalized elevated serum aminotransferase activities. The response rate in both groups did not differ significantly. Since side effects were more pronounced during combination therapy than in IFN alpha-2b monotherapy, it is suggested that treatment with IFN alpha-2b alone is preferable to a regimen of IFN alpha-2b/IL-2 applied according to the above schedule.

Adult↗
PubMed1993

Low dose alpha interferon treatment in chronic hepatitis B virus infection.

Fifty eight patients with chronic viral hepatitis B (HBV) were randomised in a prospectively controlled trial. Thirty patients were treated with 3 million units (MU) of interferon alfa-2b subcutaneously thrice weekly for four months. Twenty eight controls received no treatment. The follow up period after treatment was six months. Twenty eight treated patients and 27 controls completed the protocol. One woman in the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response. Three patients in the control group (11%) lost hepatitis B e antigen and HBV-DNA spontaneously. This finding is statistically significant (p < 0.05). The elimination of HBV markers from the serum was associated with a return to normal of serum aminotransferase activities. Reactivation of hepatitis was not observed after seroconversion.

Adolescent↗
PubMed1990

[Early prognostic significance of hepatitis B surface antigen specific circulating immune complexes in acute type B viral hepatitis].

A total of 120 patients with acute viral hepatitis B was investigated for the presence of circulating immune complexes, HBsAg-specific immune complexes, and the behavior of some other immune parameters (immunoglobulins, rosette inhibitory factor RIF, histamine induced inhibition of spontaneous rosette forming lymphocytes). Pathologically elevated levels of circulating immune complexes were seen in 89 per cent of patients, often related to extrahepatic signs in the prodromal phase. In 95.7 per cent of them, HBsAg-containing complexes were found. There were no differences in the behavior of immune complexes between patients with recovery and patients developing chronic hepatitis B. On the contrary, the levels of RIF and differences in the inhibitory effect of histamine on rosette forming test of patient's lymphocytes did allow to distinguish patients with recovery from patients with development of chronic hepatitis B early in the course.

Antigen-Antibody Complex↗
PubMed1990

[Treatment of chronic hepatitis B with interferon alpha-2b].

In a prospective randomized trial 58 patients (46 men, 12 women; mean age 41 [18-65] years) with histologically proven chronic hepatitis B and demonstration of HBs antigen and hepatitis B virus DNA in serum were randomly divided into two groups: 30 patients were treated with recombinant alpha 2b interferon. The interferon was administered subcutaneously, 3 x 10(6) IU, three times weekly for four months. 28 patients served as untreated controls. There was a six-month post-treatment follow-up. Two patients in the treatment group and one in the control group had to be excluded later. In the treatment group one patient responded completely (HBs antigen, HBe antigen and HBV-DNA negative) and eight partially (HBe antigen and HBV-DNA negative). In three patients of the control group, HBe antigen and HBV DNA were no longer demonstrated (P less than 0.05). The loss of HBV features was associated with normalization of serum transaminases activity. Reactivation of liver inflammation after seroconversion was not observed.

Adolescent↗
PubMed1990

Treatment of chronic hepatitis B with interferon alfa-2b.

A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of hepatitis B surface antigen and hepatitis B virus DNA (HBV DNA) in the serum were randomized in a prospectively controlled trial. Thirty patients were treated with 3 megaunits of recombinant interferon alfa-2b (INTRON A, R Schering-Plough, Essex Corporation) subcutaneously thrice weekly for 4 months. Twenty-eight controls received no treatment. The post-treatment follow-up period consisted of 6 months. Twenty-eight treated patients and 27 controls completed the protocol. One female patient of the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response to therapy. Three patients in the control group (11%) lost hepatitis B e antigen and HBV DNA spontaneously. This finding is statistically significant (p less than 0.05). The elimination of hepatitis B virus markers from the serum was associated with a normalization of aminotransferase activities in the serum. Reactivation of hepatitis was not observed after seroconversion.

Adult↗