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Biomedical subjects

Johannes Weber

Publications and source records attributed to Johannes Weber.

14 recordsLinked to original sources
PubMed2006

Blood-brain barrier disruption by low-frequency ultrasound.

BACKGROUND AND PURPOSE: A recent study showed a dramatic increase in cerebral hemorrhage comprising atypical locations with low-frequency ultrasound-mediated recombinant tissue plasminogen activator-thrombolysis in humans. Here, we provide a possible explanation for this phenomenon by a side effect observed in a study using the similar ultrasound device. METHODS: The study was originally undertaken to investigate by transcranial Doppler sonography, positron emission tomography and perfusion MRI whether transcranial application of wide-field low-frequency ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral small vessel disease. RESULTS: Showing no clear positive effect on cerebral hemodynamics in 4 patients and on cerebral perfusion (positron emission tomography) in 2 patients, the study has been terminated early because of a remarkable side effect in the first patient (a 62 year-old man) undergoing perfusion-MRI: detection of frontoparietal extravasation of Gadolinium contrast agent (applied during MRI perfusion imaging preinsonation) on MRI immediately postinsonation. CONCLUSIONS: Abnormal permeability of the human blood-brain barrier can be induced by wide-field low-frequency insonation. The observed excessive bleeding rate with low-frequency sonothrombolysis might thus be attributable to primary blood-brain barrier disruption by ultrasound.

Aged↗
PubMed2005

Sigma-pi energy separation in homodesmotic reactions.

A well-established quantity for specifying the aromaticity or antiaromaticity of cyclic conjugated molecules is the so-called aromatic stabilization energy (ASE), which can be derived-either experimentally or theoretically-from appropriate homodesmotic reactions. To gain further insight into the origin of aromaticity, several schemes have been devised to partition ASE into nuclear and electronic as well as sigma and pi contributions, some of which have resulted in contradictory statements about the driving force of aromatic stabilization. Currently, these contradictions have not been resolved and have resulted in a confusing distinction between two different types of aromaticity: extrinsic and intrinsic aromaticity. By investigating different homodesmotic reactions we show that, in contrast to ASE itself, the individual contributions that enter the ASE can strongly depend on the type of reaction. Caution is therefore advised if conclusions or physical interpretations are derived from the individual components. The contradictions result from the fact that some reactions suffer from an imbalance in the number of interaction terms at the two sides of the reaction equation. The concept of isointeractional reactions is introduced and results in the elimination of the imbalance. For these reactions, the contradictions disappear and the distinction between intrinsic and extrinsic aromaticity becomes unnecessary. As far as the sigma-pi partitioning is concerned, several schemes proposed in the literature are compared. Contradictory results are obtained depending on the partitioning scheme and reaction used. In this context, it is demonstrated that for the partitioning of the electron-electron interaction, the scheme introduced by Jug and Köster is the one that is most theoretically grounded.

Journal Article↗
PubMed2005

Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI.

Chronic alcohol consumption is frequently accompanied by cerebellar degeneration. The exact aetiology of alcoholic cerebellar degeneration is still a matter of debate. The aim of the present study was to investigate whether patients with chronic alcohol consumption exhibit a decrease in dentate nuclei intensity as measured by MRI, and if so, whether this decrease correlates with cerebellar atrophy as revealed by MR imaging or with clinical signs of cerebellar ataxia. A decrease in dentate nuclei intensity would indirectly indicate that iron accumulation, and therefore, oxidative stress may play a role in alcoholic cerebellar degeneration. MRI of 45 alcoholics and 44 age and sex-matched healthy control subjects was performed using a 3D-T1-weighted fast low angle shot (FLASH) echo sequence. Signal intensities of the dentate nuclei and cerebellar white matter were bilaterally measured. Planimetric measurements of cerebellar size were performed using a 3D-T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. Results demonstrated that dentate nuclei intensity was not significantly decreased in patients with chronic alcohol consumption (mean +/- SD signal intensity 65.36 +/- 13.0) if compared with control subjects (mean +/- SD signal intensity 68.95 +/- 9.4) (p = 0.15). Dentate nuclei intensity did not correlate with cerebellar size neither in control subjects nor in alcoholics. In contrast, vitamin B1 level correlated with cerebellar size in alcoholics even if the vitamin B1 concentration was within normal values (r = 0.344, p = 0.028). These results support the view that thiamine deficiency rather than direct neurotoxic effects of alcohol is the main causative factor for the development of alcoholic cerebellar degeneration.

Adolescent↗
PubMed2005

Inhibition of bacterial transglutaminase by its heat-treated pro-enzyme.

Transglutaminases form a unique family of cross-linking enzymes which may be interesting for pharmaceutical and technical purposes. Bacterial transglutaminase, differing from the eucaryotic counterparts in being independent from Ca2+ ions, is excreted by several Streptomyces species. Until now an endogenous factor regulating activated transglutaminase could not be detected. Here, we investigated whether an inhibitor of transglutaminase is excreted into the culture fluid of Streptomyces mobaraensis. We could demonstrate that heat-resistant inhibitory activity is produced after 24h of growth reaching a maximum after 72h. A two-step ion exchange chromatography purification procedure revealed co-elution of the heat-treated inhibitor with pro-transglutaminase. Experiments with wild-type and recombinant pro-transglutaminase confirmed that the precursor protein indeed inhibits the activity of the mature enzyme.

Culture Media↗
PubMed2005

Brain perfusion following single seizures.

PURPOSE: The aim of this study was to assess the regional relative interictal and postictal perfusion changes in temporal and parietal lobe epilepsy. METHODS: We investigated interictal and postictal magnet resonance perfusion changes in five patients with temporal lobe epilepsy either with hippocampal sclerosis (n = 3) or without (n = 2), and in one patient with extratemporal (parietal lobe) epilepsy. T(2)*-weighted single-shot echo-planar images were acquired after bolus application of 0.2 mmol/kg gadolinium-diethylene triamine pentaacetic acid (GD-DTPA) at baseline and after intervals of 2-12 min, 15-23 min, 28-50 min, 63-72 min, and 180-240 min. The bolus-peak ratio was calculated in regions of interest in the hippocampus (HIP), parahippocampal gyrus (PHG), thalamus (THA), cortex (COR), and white matter (WM), yielding relative perfusion changes. RESULTS: Interictally, we found relative hyperperfusion of the ictogenic side in five of six patients in the HIP. Postictally, the perfusion decreased in the HIP by 25-39% as compared to baseline, whereas the PHG showed a reverse pattern. In the late postictal phase, perfusion increased in the HIP again and decreased in the PHG. In the THA, the inter- and postictal changes were small (5-19%). COR and WM showed equivocal results. CONCLUSION: Postictal relative hypoperfusion in the HIP appears to be associated with the cessation of neuronal ictal discharge, whereas postictal hyperperfusion in the PHG lags behind and may reflect increased metabolism to restore the interictal state of neuronal excitability.

Adult↗
PubMed2005

Clinical and radiological results after parapedicular screw fixation of the thoracic spine.

OBJECT: The proximity of thoracic pedicles to the spinal cord and neurovascular structures has prompted numerous efforts to obtain proper screw placement. The aim of this study was to evaluate the feasibility and efficacy of thoracic parapedicular (intercostovertebral) screw fixation by following anatomical landmarks and using fluoroscopy. METHODS: Thoracic parapedicular screw fixation was performed in 41 patients (328 screws). Postoperative computerized tomography scans were obtained in all cases to analyze the position of each screw with respect to the pedicle rib unit, the spinal canal, and the vertebral body (VB) according to a proposed novel grading system. Additionally, screw convergence angles were calculated for each instrumented level. There was no additional morbidity associated with parapedicular screw insertion. In a single case a screw suspected of entering the spinal canal was revised without causing neurological damage. The remaining screws were placed entirely within the pedicle rib unit and VB without breaching the neural foramina, pleura, or vascular structures. CONCLUSIONS: Thoracic and thoracolumbar instability can be treated adequately and safely by using parapedicular screw fixation guided by anatomical landmarks and fluoroscopic imaging. The use of computer-aided navigation may be beneficial but does not appear to be mandatory.

Aged↗
PubMed2004

Age-related changes of the dentate nuclei in normal adults as revealed by 3D fast low angle shot (FLASH) echo sequence magnetic resonance imaging.

The aim of the present study was to investigate age-related changes in iron-deposition in dentate nuclei using iron-induced susceptibility effects in magnetic resonance imaging. MR images from 74 healthy subjects (age range 20-68 years) were obtained using a three-dimensional (3D) T1-weighted fast low angle shot (FLASH) echo sequence. Signal intensities of the dentate nuclei and cerebellar white matter were bilaterally measured independently by three blinded investigators. The signal intensities of dentate nuclei were intraindividually normalised to the corresponding signal intensities of the cerebellar white matter of corresponding slices. Mean normalised signal intensities were correlated with age and compared between different age decades and gender. Intraclass correlation coefficients were high (dentate nuclei: 0.98, cerebellar white matter: 0.75) indicating sufficient interrater reliabilities for the determination of signal intensities. Bland-Altman analysis confirmed this finding. The normalised mean signal intensity of the dentate nuclei correlated inversely with age (r = -0.462, p < 0.0001). Comparison of age decades revealed that significant decreases took place between the third and fourth decade and to a lesser degree between the fourth and fifth decade. Moreover, variability of normalised mean signal intensities of the dentate nuclei increased significantly with age (r = 0.964, p = 0.008). There were no differences of the normalised mean signal intensities between genders. The present study revealed an age-dependent decrease of signal intensities in dentate nuclei most likely reflecting an age-dependent increase in dentate iron concentration. These age-dependent changes have to be taken into account in interpretation of disease related MR changes of cerebellar nuclei in patients with degenerative or acquired cerebellar ataxia.

Adult↗
PubMed2004

Albumin targeting of damaged muscle fibres in the mdx mouse can be monitored by MRI.

Increased sarcolemmal permeability has been implicated as a major pathological event in muscular dystrophies. In our study, we evaluated whether damaged muscle fibres can be specifically targeted using albumin as a carrier. We tagged human serum albumin (HSA) with Gadolinium (Gd) and systemically applied this compound (Gd-DTPA-HSA) to wildtype and dystrophin-deficient mdx mice. We performed magnetic resonance imaging before and after intravenous administration of Gd-DTPA-HSA and found localised signal enhancement only in mdx skeletal muscle. We also examined skeletal muscle after contrast enhanced magnetic resonance imaging using anti-human albumin antibodies and demonstrated intracellular accumulation of Gd-DTPA-HSA in clusters of damaged mdx muscle fibres. Comparison of magnetic resonance imaging and histological data emphasised the value of contrast agent enhanced magnetic resonance imaging for the in vivo assessment of fibre damage in muscular dystrophies. Furthermore, our data provide evidence that albumin can be used as a carrier to target covalently bound molecules to degenerating muscle fibres.

Animals↗
PubMed2004

Brain tissue water uptake after middle cerebral artery occlusion assessed with CT.

BACKGROUND AND PURPOSE: To study whether computed tomography (CT) can measure the water content of early ischemic edema. METHODS: The authors obtained cranial CT in 5 groups of rats subjected to 1 hour (n = 8), 2 hours (n = 11), 3 hours (n = 13), 4 hours (n = 13), or 6 hours (n = 14) of right middle cerebral artery (MCA) occlusion. Immediately after CT, the authors removed the rats' brains and determined tissue water content by the dry-wet weight method. They correlated brain x-ray attenuation with brain tissue water content. RESULTS: Mean brain tissue water content remained constant in the nonischemic left hemispheres at 77.9% +/- 0.6% and increased up to 79.3% +/- 1.0% in the right hemispheres after 6 hours of permanent right MCA occlusion. X-ray attenuation remained constant in the left hemispheres at 75.6 + 2.2 Hounsfield units (HU) and decreased to 71.7 +/- 3.4 HU in the right hemispheres after 6 hours of right MCA occlusion. The decrease in x-ray attenuation correlated significantly with the increase in ischemic brain tissue water content (y = 217.3 - 1.8x x; r = .55, P < .0001). That means that a 1% increase in hemispheric tissue water content causes a decrease in x-ray attenuation of 1.8 HU. CONCLUSIONS: After MCA occlusion, immediate brain tissue net water uptake is associated with a decrease in x-ray attenuation. CT can monitor ischemic edema in an acute stroke.

Animals↗
PubMed2003

Brain diffusion after single seizures.

PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone. METHODS: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2-210 min after a seizure. RESULTS: The interictal ADC was significantly (p < 0.05) elevated in the ictogenic hippocampus in all patients with temporal lobe epilepsy. The following postictal changes of the ADC were seen: (a) decreases by maximally 25-31%, which were most pronounced in the epileptogenic zone (n = 2); (b) generalized ADC changes after generalized seizures (n = 1) or prolonged complex partial seizures (n = 2); (c) no major changes after short-lived seizures or if the time to first DWI scan was >15 min or both (n = 3); and (d) widespread bilateral ADC increases after a flumazenil-induced seizure (n = 1). CONCLUSIONS: ADC changes seen during serial postictal DWI are complex and appear to reflect origin and spread of the preceding seizure. A delineation of the epileptogenic zone appears to be possible only in complex-partial seizures of >60 s duration that do not secondarily generalize.

Adult↗
PubMed2003

Presurgical evaluation of epilepsy by brain diffusion: MR-detected effects of flumazenil on the epileptogenic focus.

PURPOSE: After focal status epilepticus, focal alterations of the apparent diffusion coefficient (ADC) have been demonstrated in the epileptogenic zone by using diffusion-weighted magnetic resonance (MR)imaging (DWI). Effects of flumazenil on an epileptogenic focus have been demonstrated by EEG recordings, but not by functional MRI. We hypothesized that dynamic spatiotemporal alterations of brain diffusion of the epileptogenic focus after application of flumazenil will be detectable by DWI and correlate with the epileptogenic zone. METHODS: Twelve adult patients considered for epilepsy surgery with medically intractable temporal lobe epilepsy (TLE; n = 7), extratemporal lobe epilepsy (ETE; n = 2), and TLE+ETE (n = 3) were prospectively examined with DWI interictally (serving as baseline) and 10 min after application of 1 mg flumazenil i.v. RESULTS: The baseline interictal ADC was significantly elevated in the hippocampus on the ictogenic side in the patients with TLE (p = 0.002) as compared with healthy volunteers. The following changes of the mean ADC were seen in different regions of interest (ROIs) after injection of flumazenil: decreases in the hippocampus on the seizure-onset side by 14.8% (p = 0.005); decreases in the parahippocampal gyrus on both sides by 6.8% (epileptogenic side; p = 0.044) or 7.9% (nonepileptogenic side; NS), respectively; decreases in the cortex on the nonictogenic side by 7.9% (p = 0.047); and no significant changes of the ADC in the other ROIs. CONCLUSIONS: ADC decreases measured after application of flumazenil were seen in the seizure-onset zone as revealed by EEG and structural MRI and are an indicator of focus localization in patients with TLE.

Adult↗
PubMed2002

Eyeblink-related areas in human cerebellum as shown by fMRI.

Classical eyeblink conditioning is used frequently to study the role of the cerebellum in associative learning. To understand the mechanisms involved in learning, the neural circuits that generate the eyeblink response should be identified. The goal of the present study was to examine cerebellar regions that are likely to control the human eyeblink response using event-related functional magnetic resonance imaging (fMRI). In 14 healthy volunteers eyeblinks were evoked by unilateral air-puff stimulation (total of 30 stimuli, inter-trial interval 27-44 sec). With eyes closed throughout the experiment, eyeblinks were recorded using a video-based system with infrared reflecting markers being attached to the upper eyelids. From each subject 500 scans were taken (TR = 2.2 sec, 22 slices per scan, slice thickness = 3 mm) using an echo planar imaging sequence (EPI). The statistical parametric maps of the experimental volume images were estimated with SPM99 specifying an appropriate event-related design matrix. Two main regions of significant activation were found in the ipsilateral posterior lobe of the cerebellar hemisphere. In the more anterior region the maxima of activation were located in hemispheral lobules VI and Crus I, and in the more posterior region in hemispheral lobules VIIb, Crus II and VIIIa (nomenclature according to Schmahmann et al. [2000]: MRI Atlas of the Human Cerebellum). Although less pronounced, activity was found also in corresponding areas of the contralateral cerebellar hemisphere. These eyeblink-related areas agree with trigeminal projection areas and blink reflex control areas shown in previous animal studies.

Adult↗
PubMed2002

Brain representation of hemifield stimulation in poststroke visual field defects.

BACKGROUND AND PURPOSE: Plasticity in extended, parallel, or reciprocal operating networks is well recognized. Changes in neuronal activity after lesions to distinct localized structures, such as the primary visual cortex, are less well characterized. We investigated the cortical reorganization in patients with poststroke visual field defects using blood oxygen level-dependent functional MRI. METHODS: Brain activation was measured in 7 patients with a single occipital cortical lesion and partially recovered hemianopia and in 7 age-matched control subjects. Differences in activation between rest and visual hemifield stimulation were assessed with statistical parametric mapping (SPM'99). RESULTS: In normal subjects, significant activation was found in the contralateral primary visual cortex and bilaterally in the extrastriate cortex. During hemifield stimulation of the unaffected side of stroke patients, a similar pattern was found compared with that seen in control subjects. During stimulation of the hemianopic side, bilateral activation was seen within the extrastriate cortex, stronger in the ipsilateral hemisphere. The primary visual cortex was not significantly activated in either hemisphere during stimulation of the hemianopic side. CONCLUSIONS: Visual field defects after stroke are associated with bilateral activation of the extrastriate visual cortex. This pattern of activation indicates altered neuronal activity in the visual system. Further investigation is necessary to determine the relationship between functional reorganization and recovery of lost visual function after poststroke hemianopia.

Adult↗