Biomedical subjects

W D Heiss

Publications and source records attributed to W D Heiss.

At least 19 recordsLinked to original sources

PubMed2006

Primary stroke unit treatment followed by very early carotid endarterectomy for carotid artery stenosis after acute stroke.

BACKGROUND: Although it is recognized that carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the past, very early CEA has been shown to carry substantial risks. We assessed an interdisciplinary concept of very early CEA in patients with high-grade (>70%) symptomatic ICA stenosis at a single center. PATIENTS AND METHODS: The course of treatment and outcomes of patients who underwent CEA as early as possible after being referred to the stroke unit for symptoms of transient ischemic attack and stroke were prospectively evaluated, including the following parameters: age, severity of ischemia-related symptoms according to the modified Rankin scale, duration of symptoms until admission, multimodal imaging findings (color-coded duplex, cranial computed tomography, magnetic resonance imaging, positron emission tomography), duration until CEA, perioperative course and complications, as well as duration of in-hospital care. RESULTS: Fifty consecutive patients (median age 68 years, range 44-90) with clinical and imaging signs of transient ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until December 2004. All except 1 patient showed a preoperative Rankin < 4. There was a median time period of 6 h between the onset of symptoms and admission (range 1 h to 15 days) and a median duration of 4 days after admission until operation (range 1-21 days). Seven patients underwent CEA of the contralateral, severely stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients who primarily underwent systemic thrombolysis recovered almost completely. Three patients (6%) experienced a clinical deterioration before surgery. In the majority of patients (43/50), CEA was performed under local anesthesia with selective shunt use which became necessary in 26%. Three patients (6%) had postoperative worsening due to new infarcts. In 2 cases, an intracerebral hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical revision was necessary because of an ICA thrombosis without permanent neurological decline. Patients were discharged after a median time of 14.5 days (range 4-44). CONCLUSIONS: After careful selection and preparation in a stroke unit, patients with acute stroke due to carotid stenosis can undergo very early CEA under local anesthesia with a perioperative risk comparable with the risk of later endarterectomy, therefore preventing very early stroke recurrences.

Adult↗

PubMed2006

[Fatal familial insomnia: case presentation and discussion of typical clinical and imaging findings].

Fatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20. It is characterized by disturbed night sleep, resulting in daily vigilance perturbations and a variety of other neurological symptoms. We present the case of a 46-year-old woman deteriorating despite immunosuppressive treatment which was initiated suspecting cerebral vasculitis as the cause of her progressive neurological symptoms. The correct diagnosis was established only post mortem. Based on the case presented here, we discuss typical clinical symptoms and imaging findings. In particular, we outline how modern diagnostic methods such as positron emission tomography with [(15)O]H(2)O and [(18)F]FDG and single photon emission computed tomography can add valuable information to results from conventionally performed imaging techniques and genetic testing.

Fatal Outcome↗

PubMed2006

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.

Adult↗

PubMed2005

Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways.

OBJECTIVE: To assess neurochemical deficits in patients with Parkinson disease (PD) associated dementia (PDD) in vivo. METHODS: The authors performed combined PET with N-[11C]-methyl-4-piperidyl acetate (MP4A) and 18F-fluorodopa (FDOPA) for evaluation of cholinergic and dopaminergic transmitter changes in 17 non-demented patients with PD and 10 patients with PDD. Data were compared to 31 age-matched controls by a combined region-of-interest and voxel-based Statistical Parametric Mapping analysis. RESULTS: The striatal FDOPA uptake was significantly decreased in PD and PDD without differences between the groups. The global cortical MP4A binding was severely reduced in PDD (29.7%, p < 0.001 vs controls) and moderately decreased in PD (10.7%, p < 0.01 vs controls). The PDD group had lower parietal MP4A uptake rates than did patients with PD. Frontal and temporo-parietal cortices showed a significant covariance of striatal FDOPA reduction and decreased MP4A binding in patients with PDD. CONCLUSIONS: While non-demented patients with Parkinson disease had a moderate cholinergic dysfunction, subjects with Parkinson disease associated dementia (PDD) presented with a severe cholinergic deficit in various cortical regions. The finding of a closely associated striatal FDOPA and cortical MP4A binding reduction suggests a common disease process leading to a complex transmitter deficiency syndrome in PDD.

Acetates↗

PubMed2005

Large-N scaling behavior of the Lipkin-Meshkov-Glick model.

We introduce a novel semiclassical approach to the Lipkin model. In this way the well-known phase transition arising at the critical value of the coupling is intuitively understood. New results--showing for strong couplings the existence of a threshold energy which separates deformed from undeformed states as well as the divergence of the density of states at the threshold energy--are explained straightforwardly and in quantitative terms by the appearance of a double well structure in a classical system corresponding to the Lipkin model. Previously unnoticed features of the eigenstates near the threshold energy are also predicted and found to hold.

Journal Article↗

PubMed2004

Encircling an exceptional point.

We calculate analytically the geometric phases that the eigenvectors of a parametric dissipative two-state system described by a complex symmetric Hamiltonian pick up when an exceptional point (EP) is encircled. An EP is a parameter setting where the two eigenvalues and the corresponding eigenvectors of the Hamiltonian coalesce. We show that it can be encircled on a path along which the eigenvectors remain approximately real and discuss a microwave cavity experiment, where such an encircling of an EP was realized. Since the wave functions remain approximately real, they could be reconstructed from the nodal lines of the recorded spatial intensity distributions of the electric fields inside the resonator. We measured the geometric phases that occur when an EP is encircled four times and thus confirmed that for our system an EP is a branch point of fourth order.

Journal Article↗

PubMed2003

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

Alzheimer Disease↗

PubMed2003

Observation of a chiral state in a microwave cavity.

A microwave experiment has been realized to measure the phase difference of the oscillating electric field at two points inside the cavity. The technique has been applied to a dissipative resonator which exhibits a singularity-called exceptional point-in its eigenvalue and eigenvector spectrum. At the singularity, two modes coalesce with a phase difference of pi/2. We conclude that the state excited at the singularity has a definitive chirality.

Journal Article↗

PubMed2003

Significant shrinkage of extracellular space during global cerebral ischemia: differences in gray and white matter ischemia.

Brain extracellular space (ECS) provides an important microenvironment for neurons and glial cells. In the present study, we investigated differences in ischemic changes of ECS in gray and white matter during global ischemia in cats (n = 8). Diffusion capacity of tetramethylammonium ion (TMA+, 74.1Da) was evaluated by measuring extracellular TMA+ concentration applied via microdialysis. In both gray and white matter, TMA+ concentration significantly increased within 10 minutes after the induction of ischemia, and sustained during 120 min of ischemia. The increase, however, was slower and smaller in white matter than in gray matter. In other two animals, volume fraction and tortuosity of ECS were determined by iontophoresis during global ischemia. After 30 min of ischemia induction, volume fraction was decreased and tortuosity was increased in both gray and white matter. In white matter, decrease in volume fraction and increase in tortuosity were smaller than in gray matter. The present study demonstrates that cerebral ischemia induces not only significant shrinkage of ECS volume but also restricts molecular diffusion within. Smaller changes of diffusion capacity within white matter ECS during ischemia may be relevant for lower ischemic vulnerability of the region.

Animals↗

PubMed2003

Prediction of malignant infarction: perifocal neurochemical monitoring following prolonged MCA occlusion in cats.

Neurochemical monitoring in the ischemic core predicts malignancy in focal ischemia in cats. Since perifocal regions are more suitable for clinical microdialysis (MD) applications, we tested whether monitoring at such site predicts also malignancy.--Laser Doppler (LD) probes, pressure microsensors, and MD/HPLC measured cerebral blood flow (CBF), intracranial pressure (ICP), and extracellular glutamate (Glu), respectively. The middle cerebral artery was occluded (MCAO) for 3 hours followed by 6 hours reperfusion. Additionally, LD measured CBF in ischemic core.--MCAO reduced CBF in the core in all below 25% of control. In animals exhibiting malignancy (eye dilatation during reperfusion), MCAO decreased CBF in the perifocal site to around 35%. CBF primarily recovered following recirculation but decreased thereafter as ICP rose due to progressive edema formation. Glu increased concomitantly. In cats exhibiting a benign course, MCAO decreased CBF in the perifocal site to around 55%. Recirculation normalized CBF, and Glu did not increase. During MCAO, Glu differences between both groups were not significant.--Glu determinations in perifocal sites taken during MCAO do not predict fatal outcome. This contrasts with determinations in the core. After reperfusion, Glu elevation in perifocal sites may serve as a rather late predictor of malignancy.

Animals↗

PubMed2003

Identification of malignant brain edema after hemispheric stroke by PET-imaging and microdialysis.

Cerebral blood flow (CBF) and extent of irreversible tissue damage as well as the time course of extracellular concentration of amino acids, substrates of energy metabolism, and purine metabolites, intracranial pressure and tissue oxygen tension were assessed in 34 patients with large strokes covering more than 50% of the MCA territory. The results were compared to findings in the experimental model of transient (for 3 hours) MCA occlusion in cats. In the experimental model as well as in the clinical setting development of malignant brain infarcts (due to formation of space occupying brain edema) was predicted by the size of critically hypoperfused tissue and the volume of irreversibly damaged tissue. The course of malignant infarcts was characterized by progressive increase in concentrations of excitatory amino acids, lactate, pyruvate, glycerol, hypoxanthine and in intracranial pressure, while cerebral perfusion pressure and tissue oxygen tension decreased. These results clearly differentiate a malignant from a benign course of large hemispheric infarction. The methods can be used to identify patients at risk for formation of space occupying edema and to select patients who could benefit from invasive therapeutic strategies.

Amino Acids↗

PubMed2003

Imaging in gene therapy of patients with glioma.

Over 10 years ago, the first successful gene therapy paradigms for experimental brain tumors models have been conducted, and they were thought to revolutionize the treatment of patients with gliomas. Application of gene therapy has been quickly forced into clinical trials, the first patients being enrolled in 1994, with overall results being disappointing. However, single patients seemed to benefit from gene therapy showing long-term treatment response, and most of these patients bearing small glioblastomas. Whereas the gene therapy itself has been performed with high sophistication, limited attention has been paid on technologies, which (i) allow an identification of viable target tissue in heterogenous glioma tissue and which (ii) enable an assessment of successful vector administration and vector-mediated gene expression in vivo. However, these measures are a prerequisite for the development of successful gene therapy in the clinical application. As biological treatment strategies such as gene and cell-based therapies hold promise to selectively correct disease pathogenesis, successful clinical implementation of these treatment strategies rely on the establishment of molecular imaging technology allowing the non-invasive assessment of endogenous and exogenous gene expression in vivo. Imaging endogenous gene expression will allow the characterization and identification of target tissue for gene therapy. Imaging exogenously introduced cells and genes will allow the determination of the 'tissue dose' of transduced cell function and vector-mediated gene expression, which in turn can be correlated to the induced therapeutic effect. Only these combined strategies of non-invasive imaging of gene expression in vivo will enable the establishment of safe and efficient vector administration and gene therapy protocols for clinical application. Here, we review some aspects of imaging in gene therapy trials for glioblastoma, and we present a 'proof-of-principle' 2nd-generation gene therapy protocol integrating molecular imaging technology for the establishment of efficient gene therapy in clinical application.

Brain↗

PubMed2003

Monitoring the effect of chemotherapy in a mixed glioma by C-11-methionine PET.

The effect of chemotherapy with procarbazine, CCNU, and vincristine in an anaplastic oligoastrocytoma was monitored by repeated positron emission tomography (PET) with C-11-methionine (C-11-MET). Chemotherapy caused a continuous decline of active tumor volume at a rate of approximately 2.4% per day, resulting in complete remission that persisted until the end of follow-up at 3 years. Thus, the authors conclude that C-11-MET PET may be useful for monitoring chemotherapy in gliomas and deserves further study.

Adult↗

PubMed2002

HeinzelCluster: accelerated reconstruction for FORE and OSEM3D.

Using iterative three-dimensional (3D) reconstruction techniques for reconstruction of positron emission tomography (PET) is not feasible on most single-processor machines due to the excessive computing time needed, especially so for the large sinogram sizes of our high-resolution research tomograph (HRRT). In our first approach to speed up reconstruction time we transform the 3D scan into the format of a two-dimensional (2D) scan with sinograms that can be reconstructed independently using Fourier rebinning (FORE) and a fast 2D reconstruction method. On our dedicated reconstruction cluster (seven four-processor systems, Intel PIII@700 MHz, switched fast ethernet and Myrinet, Windows NT Server), we process these 2D sinograms in parallel. We have achieved a speedup > 23 using 26 processors and also compared results for different communication methods (RPC, Syngo, Myrinet GM). The other approach is to parallelize OSEM3D (implementation of C Michel), which has produced the best results for HRRT data so far and is more suitable for an adequate treatment of the sinogram gaps that result from the detector geometry of the HRRT. We have implemented two levels of parallelization for four dedicated cluster (a shared memory fine-grain level on each node utilizing all four processors and a coarse-grain level allowing for 15 nodes) reducing the time for one core iteration from over 7 h to about 35 min.

Algorithms↗

PubMed2002

Universal relationship between a quantum phase transition and instability points of classical systems.

The direct and universal relationship between the accumulation of exceptional points in the quantum spectrum at a phase transition and the singularity of the classical action at a homoclinic point of the separatrix is investigated. The particular common features are the analytic structure and, related to it, instability and high sensitivity leading generically to the onset of chaos in both cases under perturbation.

Journal Article↗

PubMed2002

Towards non-invasive imaging of HSV-1 vector-mediated gene expression by positron emission tomography.

The overall goals of the broad and growing field of molecular medicine is to identify fundamental errors of disease and to develop corrections of them on the molecular level. At the same time, real-time imaging of gene expression in vivo aims towards a detailed analysis of both endogenous and exogenous gene expression in animal models of disease and in the clinical setting. Non-invasive imaging of endogenous gene expression may reveal insight into the molecular basis of disease pathogenesis and the extent of treatment response. When exogenous genes are introduced, e.g. by herpes simplex virus type 1 (HSV-1)-based vectors, to ameliorate a genetic defect or to add an additional gene function to cells, imaging techniques may reveal the assessment of the location, magnitude and duration of therapeutic gene expression and its correlation to the therapeutic effect. Here, we review the main approaches of non-invasive imaging techniques of gene expression in vivo with special reference to HSV-1 vector-mediated gene expression.

Animals↗

PubMed2002

Quantum dispersion and its exponential growth of a wave packet in chaotic systems.

The quantum correspondence of one particular signature of classical chaos--the exponential instability of motion--can be characterized by the initial exponential growth rate of the spreading of the propagating quantum wave packet. The growth rate is approximately twice the classical maximum Lyapunov exponent of the system. In the regular case, the dispersion of the wave packet is only due to the usual quantum effect that should vanish in the classical limit. In contrast, in the chaotic case, the evolution behavior of the wave packet is due to the dynamical effect associated with the nonlinearity and persists as long as the spatial extension of the initial wave packet is kept finite.

Journal Article↗

PubMed2002

Prospects of molecular imaging in neurology.

Molecular imaging aims towards the non-invasive kinetic and quantitative assessment and localization of biological processes of normal and diseased cells in vivo in animal models and humans. Due to technological advances during the past years, imaging of molecular processes is a rapidly growing field, which has the potential of broad applications in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, characterization of transgenic animals, development of new treatment strategies (gene or cell-based) and their successful implementation into clinical application. Most importantly, the possibility to study these parameters in the same subject repeatedly over time makes molecular imaging an attractive technology to obtain reliable data and to safe recourse; for example, molecular imaging enables the assessment of an exogenously introduced therapeutic gene and the related alterations of endogenously regulated gene functions directly in the same subject. Therefore, molecular imaging will have great implications especially when molecular diagnostic and treatment modalities have to be translated from experimental into clinical application. Here, we review the three main imaging technologies, which have been developed for studying molecular processes in vivo, the disease models, which have been studied so far, and the potential future applications.

Animals↗