PubMed Health⌕ Search

Biomedical subjects

E Busch

Publications and source records attributed to E Busch.

At least 19 recordsLinked to original sources
PubMed2005

[Thrombophilias in patients with ischemic stroke. Indication and calculated costs for evidence-based diagnostics and treatment].

Patients with ischemic stroke are sometimes found to have an underlying inherited (deficiency of protein C, protein S, antithrombin III, activated protein C resistance, prothrombin gene mutation, hyperhomocysteinemia) or acquired thrombophilia (lupus anticoagulant and anticardiolipin antibodies, hyperhomocysteinemia). Patient selection for thrombophilia screening is, therefore, a frequent question in managing patients with ischemic stroke. In this review we discuss patient selection and timing for laboratory tests for thrombophilia screening in stroke patients based on a literature review and we calculated overall costs per year in Germany for testing patients older than 18 years with an ischemic stroke of undetermined cause. As there is a lack of studies comparing anticoagulation with antiplatelet therapy in patients with diagnosed thrombophilia, laboratory screening for thrombophilia even in a selected group of patients with cryptogenic ischemic stroke remains of questionable value at present. An exception appears to be testing for lupus anticoagulant and anticardiolipin antibodies in younger patients with suspected antiphospholipid syndrome (two positive test results necessary), because anticoagulation seems to be superior to aspirin in patients with antiphospholipid syndrome.

Brain Ischemia↗
PubMed2001

Changes in apparent diffusion coefficients of metabolites in rat brain after middle cerebral artery occlusion measured by proton magnetic resonance spectroscopy.

Diffusion-weighted proton MR spectroscopy and imaging have been applied to a rat brain model of unilateral middle cerebral artery occlusion between 1 and 4 hr post occlusion. Similar apparent diffusion coefficients (ADC) of most metabolites were observed within each hemisphere. In the ischemic ipsilateral hemisphere, the ADCs were (0.083--0.116). 10(-3) mm(2)/sec for lactate (Lac), alanine (Ala), gamma-amino butyric acid (GABA), N-acetyl aspartate (NAA), glutamine (Gln), glutamate (Glu), total creatine (tCr), choline-containing compounds (Cho), and myo-inositol (Ins), in the contralateral hemisphere (0.138--0.158). 10(-3) mm(2)/sec for NAA, Glu, tCr, Cho, and Ins. Higher ADCs was determined for taurine (Tau) in the ipsilateral (0.144. 10(-3) mm(2)/sec) and contralateral (0.198. 10(-3) mm(2)/sec) hemisphere. In the ischemic hemisphere, a relative ADC decrease to 65--75% was observed for NAA, Glu, tCr, Cho, Ins and Tau, which was similar to the decrease of the water ADC (to 67%). The results suggest a common cause of the observed ADC changes and provide a broader experimental basis to evaluate theories of water and metabolite diffusion. Magn Reson Med 45:383-389, 2001.

Animals↗
PubMed2000

Calcium affinity, cooperativity, and domain interactions of extracellular EF-hands present in BM-40.

The structure and function of cytosolic Ca(2+)-binding proteins containing EF-hands are well understood. Recently, the presence of EF-hands in an extracellular protein was for the first time proven by the structure determination of the EC domain of BM-40 (SPARC (for secreted protein acidic and rich in cysteine)/osteonectin) (Hohenester, E., Maurer, P., Hohenadl, C., Timpl, R., Jansonius, J. N., and Engel, J. (1996) Nat. Struct. Biol. 3, 67-73). The structure revealed a pair of EF-hands with two bound Ca(2+) ions. Two unusual features were noted that distinguish the extracellular EF-hands of BM-40 from their cytosolic counterparts. An insertion of one amino acid into the loop of the first EF-hand causes a variant Ca(2+) coordination, and a disulfide bond connects the helices of the second EF-hand. Here we show that the extracellular EF-hands in the BM-40 EC domain bind Ca(2+) cooperatively and with high affinity. The EC domain is thus in the Ca(2+)-saturated form in the extracellular matrix, and the EF-hands play a structural rather than a regulatory role. Deletion mutants demonstrate a strong interaction between the EC domain and the neighboring FS domain, which contributes about 10 kJ/mol to the free energy of binding and influences cooperativity. This interaction is mainly between the FS domain and the variant EF-hand 1. Certain mutations of Ca(2+)-coordinating residues changed affinity and cooperativity, but others inhibited folding and secretion of the EC domain in a mammalian cell line. This points to a function of EF-hands in extracellular proteins during biosynthesis and processing in the endoplasmic reticulum or Golgi apparatus.

Amino Acid Motifs↗
PubMed2000

Spreading waves of transient and prolonged decreases in water diffusion after subarachnoid hemorrhage in rats.

Diffusion-weighted MRI (DWI), which can detect cortical spreading depressions (SDs) as propagating waves of reduced apparent diffusion coefficient (ADC) of water, was used to investigate whether spreading depression occurs after subarachnoid hemorrhage (SAH) induced by endovascular perforation in the rat. Eleven rats underwent SAH while positioned in the magnet. The ADC measurements had a temporal resolution of 12 sec. Transient decreases in ADC to 74 +/- 5% of pre-SAH values were observed in three rats after SAH, which propagated over the cortex with an average speed of 4.2 +/- 0. 6 mm/min, consistent with an SD wave. Furthermore, in all 11 rats, a wavefront of reduced ADC, which did not resolve within the 12 min observation period, spread at a speed of 3.2 +/- 1.7 mm/min in the ipsilateral cortex, and again is consistent with the speed of SD propagation. Therefore, spreading depression-like cellular depolarization is a consequence of acute subarachnoid hemorrhage in rats. Magn Reson Med 44:110-116, 2000.

Animals↗
PubMed2000

Penumbral tissue alkalosis in focal cerebral ischemia: relationship to energy metabolism, blood flow, and steady potential.

The effect of focal ischemia on tissue pH was studied at various times up to 6 hours after permanent middle cerebral artery occlusion in rats. Tissue pH was imaged by using umbelliferone fluorescence and correlated with cerebral blood flow, ATP content, and recordings of the steady potential. Circumscribed foci of allalosis (pH 7.32+/-0.11) were detected with increasing frequency in penumbral regions having near-to-normal ATP concentrations and cerebral blood flow values between 20% and 40% of control. Both the infarct core, defined by ATP loss and cerebral blood flow values of less than 20% of control, and the inner peri-infarct rim were consistently acidic (pH 6.03+/-0.36 and 6.53+/-0.24, respectively). Treatment with the glutamate antagonist dizocilpine (MK-801) suppressed negative shifts of the steady potential and reduced significantly the occurrence of alkalosis observed in 90% of untreated but only in 44% of treated animals. Penumbral alkalosis appeared to be a time-dependent event occurring 30 to 60 minutes after the passage of peri-infarct depolarizations. The diversity of penumbral pH changes reflects the local disturbance of pH regulation and, possibly, the differential fate of penumbral subareas.

Acidosis↗
PubMed2000

Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York.

To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out.

Adipose Tissue↗
PubMed1999

Simultaneous recording of evoked potentials and T2*-weighted MR images during somatosensory stimulation of rat.

Somatosensory evoked potentials (SEP) and T2*-weighted nuclear magnetic resonance (NMR) images were recorded simultaneously during somatosensory stimulation of rat to investigate the relationship between electrical activation of the brain tissue and the signal intensity change in functional NMR imaging. Electrical forepaw stimulation was performed in Wistar rats anesthetized with alpha-chloralose. SEPs were recorded with calomel electrodes at stimulation frequencies of 1.5, 3, 4.5, and 6 Hz. At the same time, T2*-weighted imaging was performed, and the signal intensity increase during stimulation was correlated with the mean amplitude of the SEP. Both the stimulation-evoked signal intensity increase in T2*-weighted images and the amplitude of SEPs were dependent on the stimulation frequency, with the largest signals at a stimulation frequency of 1.5 Hz and decreasing activations with increasing frequencies. The feasibility of simultaneous, artifact-free recordings of T2*-weighted NMR images and of evoked potentials is proved. Furthermore, the study demonstrates-in the intact brain-the validity of functional magnetic resonance imaging for estimating the intensity of electrocortical activation.

Animals↗
PubMed1999

High-resolution mapping of discrete representational areas in rat somatosensory cortex using blood volume-dependent functional MRI.

The present study documents the use of an iron oxide-based blood-pool contrast agent in functional magnetic resonance imaging to monitor activity-related changes in cerebral blood volume (CBV) resulting from peripheral sensory stimulation and the application of this technique to generate high-resolution functional maps. Rats, anesthetized with alpha-chloralose, were imaged during electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps were generated by cross-correlation of the measured signal response and a square-wave function representative of the stimulus for each image pixel. Multislice imaging produced functional maps consistent with the known functional anatomy of rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution demonstrated rapid (<6 s) CBV increases which were sustained and relatively stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation periods of up to 5 min. Enabled by this sustained response we generated high-resolution (approximately 100 micrometer in-plane) functional maps showing discrete forelimb and hindlimb activation. This technique offers many advantages over other methods for the study of brain activity in the rat and has resolution sufficient to be useful in reorganization studies.

Animals↗
PubMed1998

Magnetization transfer attenuates metabolite signals in tumorous and contralateral animal brain: in vivo observations by proton NMR spectroscopy.

Tumorous and contralateral rat brain was examined by in vivo single voxel proton NMR spectroscopy. Magnetization transfer (MT) experiments cause attenuation of various metabolite signals. Selective saturation of immobile metabolites was achieved by pulsed RF preirradiation. The method is compared with continuous wave MT generation. In contralateral tissue, MT attenuation is detected for both the CH3 and the CH2 protons of (phospho-)creatine (Cr + PCr) and for a signal at 3.44 ppm ascribed to taurine. Significant attenuation is also observed for a signal at 3.78 ppm that is commonly ascribed to the alphaCH proton of glutamate and glutamine (Glx); however, no effect is observed for the gammaCH2 protons of Glx. Within implanted F98 glioma tumors, only the CH3 signal of Cr + PCr shows significant MT attenuation. Although the MT effect detected for lactate in the tumors fails to reach significance, a significant effect is observed for the lactate signal acquired during 3 to 9 min postmortem.

Animals↗
PubMed1998

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging.

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N-acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from 163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.

Animals↗
PubMed1998

A prospective, randomized 5-year follow-up study of functional restoration in chronic low back pain patients.

A functional restoration (FR) program, dealing with a combination of intensive physical and ergonomic training, psychological pain management, and patient education, was tested in two randomized, parallel group studies. In one of these patients following the FR program were compared with a non-treated control group (project A), and in the other with patients on two less intensive treatment programs (project B). A total of 238 chronic low back pain patients participated in the two studies, 106 entering project A and 132 project B. Patients from the two projects were comparable except that the patients in project A were recruited from all over the country, whereas patients in project B all were living in and around Copenhagen. Thirteen patients never started any treatment, and 20 patients (9%) dropped out during the treatment period. Of the 207 who completed treatment, 89% returned a mailed questionnaire 5 years later. This was the case for 55% of the drop-outs. The questions referred to work situation, pain level, activities of daily living, days of sick leave, contact with health care professionals, physical activity, use of medication, and a subjective overall assessment. The results show that in project A the treated group reported significantly fewer contacts with the health care system and significantly fewer days of sick leave over the 5-year follow-up period compared to the control group. In all other parameters, including work ability, there was no statistically significant difference between the two groups. In project B, patients treated in the FR program did significantly better in most measured parameters, except in leg pain, use of pain medication and sport activity, where no significant differences were found between groups. The overall result shows a positive long-term effect of the FR program, but it also shows the necessity of testing a given treatment in different projects and designs, among other things due to statistical variations.

Absenteeism↗
PubMed1998

Superior survival of young women with malignant melanoma.

BACKGROUND: The Commission on Cancer data from the National Cancer Data Base (NCDB) relating to patients with malignant melanoma are used to examine patterns of long-term survival by patient gender and age, stage of disease, disease morphology, and anatomic subsite. METHODS: Five calls for data have yielded more than 3,700,000 cases of cancer for the years 1985 through 1993, including 23,341 cases of malignant melanoma between 1985 and 1989, from hospital cancer registries across the US, representing slightly less than a quarter of all melanoma cases diagnosed in the US between 1985 and 1989. RESULTS: Three statements can be made from this data: (1) There is little difference in the frequency of malignant melanoma between men and women with respect to stage of disease or morphology. However, differences between the genders do appear with respect to the anatomic subsite of melanotic tumors. (2) Overall, young women (45 years of age and under) enjoy superior survival rates when compared with older women (55 years of age and older) and men of any age. (3) The survival advantage held by young women is particularly pronounced among patients diagnosed with advanced stage disease. CONCLUSIONS: These data suggest that factors present in younger women may be critical in the superior survival rates seen among premenopausal women and might be hormonal in nature.

Age Factors↗
PubMed1998

Reperfusion after thrombolytic therapy of embolic stroke in the rat: magnetic resonance and biochemical imaging.

The effect of thrombolytic therapy was studied in rats submitted to thromboembolic stroke by intracarotid injection of autologous blood clots. Thrombolysis was initiated after 15 minutes with an intracarotid infusion of recombinant tissue-type activator (10 mg/kg body weight). Reperfusion was monitored for 3 hours using serial perfusion- and diffusion magnetic resonance imaging, and the outcome of treatment was quantified by pictorial measurements of ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in an immediate decrease in blood flow and a sharp decrease in the apparent diffusion coefficient (ADC) that persisted throughout the observation period. Thrombolysis successfully recanalized the embolized middle cerebral artery origin and led to gradual improvement of blood flow and a slowly progressing reversal of ADC changes in the periphery of the ischemic territory, but only to transient and partial improvement in the center. Three hours after initiation of thrombolysis, the tissue volume with ADC values less than 80% of control was 39 +/- 22% as compared to 61 +/- 20% of ipsilateral hemisphere in untreated animals (means +/- SD, P = .03) and the volume of ATP-depleted brain tissue was 25 +/- 31% as compared to 46 +/- 29% in untreated animals. Recovery of ischemic brain injury after thromboembolism is incomplete even when therapy is started as early as 15 minutes after clot embolism. Possible explanations for our findings include downstream displacement of clot material, microembolism of the vascular periphery, and events associated with reperfusion injury.

Adenosine Triphosphate↗
PubMed1998

Characterization of middle cerebral artery occlusion infarct development in the rat using fast nuclear magnetic resonance proton spectroscopic imaging and diffusion-weighted imaging.

A nuclear magnetic resonance study of the middle cerebral artery occlusion in the rat is presented. Experiments were performed on seven animals before and after occlusion, which occurred in situ. The emphasis in this study was on evaluating rapid proton spectroscopic imaging. Data were acquired with experimental durations of between 4 and 15 minutes for a 32 by 32 spatial matrix, with 64 spectroscopic data points per spatial element. The spectroscopic data were interleaved with diffusion-weighted nuclear magnetic resonance water images of the same slice. The study was terminated at about 6 hours after occlusion. The brains were then frozen in liquid nitrogen for biochemical imaging. The results showed that the signal from N-acetyl aspartate decreased and that of lactate increased within the infarcted region. The temporal course of these intensity changes varied between animals. Nineteen cortical spreading depressions (CSD) were observed by electrophysiologic monitoring during the experiments. Of these, 11 could be unambiguously detected in the lactate images, and a further 3 were on the threshold of detectability. As only a single slice could be examined, it is possible that the centers of depression for the remaining 6 CSD were outside the slice. To the authors' knowledge, this is the first report of the measurement of CSD using proton spectroscopic imaging. Thus, it is shown that this method is valuable not only in following the continuous evolution of proton metabolites with a good spatial and temporal resolution, but also in observing transient phenomena which are believed to play an important role in the expansion of the infarcted territory.

Animals↗
PubMed1998

Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat: potential mechanisms studied by magnetic resonance imaging.

Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin (PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA (N=6), (2) human serum albumin (N =6), and (3) saline (N=7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging--derived hemispheric lesion volume in the PNA-treated group (25%+/-9%) was significantly smaller than that in the saline-treated (43%+/-13%; P=0.016) or albumin-treated groups (38%+/-6%; P=0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8%+/-7%), saline (35%+/-8%; P < 0.001), and albumin (31%+/-6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.

Animals↗
PubMed1998

High-resolution functional magnetic resonance imaging of the rat brain: mapping changes in cerebral blood volume using iron oxide contrast media.

Contrast-enhanced magnetic resonance imaging was used to produce high-resolution activation maps reflecting local changes in cerebral blood volume after a simple sensory stimulus. Activation of the forelimb region of the somatosensory cortex was performed in alpha-chloralose-anaesthetized rats with an electrical stimulus (5 V, 3 Hz) delivered through needle electrodes placed subcutaneously on the left forelimb. A gradient echo magnetic resonance imaging sequence, sensitive to changes in the relative amount of deoxyhemoglobin within the cerebral vasculature, produced a 4.05%+/-1.69% increase in signal intensity. This effect was enhanced with an injection of an intravascular iron oxide contrast agent (Combidex, Advanced Magnetics), resulting in a 9.11%+/-1.52% decrease in signal intensity.

Animals↗
PubMed1998

Diffusion MR imaging during acute subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: We analyzed the temporal and spatial pattern of water diffusion changes during acute subarachnoid hemorrhage (SAH) in rat brain to identify factors contributing to the acute pathophysiology of SAH. METHODS: Subarachnoid hemorrhage was remotely induced via perforation of the circle of Willis with an endovascular suture during MR imaging. A fast echo-planar imaging technique was used to acquire 60 maps of the apparent diffusion coefficient (ADC) beginning 1 min before and continuing for 11 min after induction of SAH. A high-resolution spin-echo diffusion sequence was used to follow diffusion changes over 6 h after SAH. Sham-operated control (n=3), nonheparinized (n=6), and heparinized (n=5) groups were studied. RESULTS: Sham-operated control animals did not show ADC changes over time. In both SAH groups, however, a sharp decline of ADC within 2 min of SAH was consistently observed in the ipsilateral somatosensory cortex. These decreases in diffusion then spread within minutes over the ipsilateral hemisphere. Similar ADC decreases on the contralateral side started with a further time delay of 1 to 3 min. From 30 min onward, the extent of the diffusion abnormality decreased progressively in the nonheparinized animals. No recovery was observed in heparinized rats. CONCLUSIONS: MR diffusion imaging allows new insight into the pathophysiology of acute SAH: The spatial and temporal pattern of diffusion changes suggests the initial occurrence of acute vasospasm and subsequently "spreading depolarization" of brain tissue. Persistent hemorrhage in heparinized animals was reflected by early decline of ADC values throughout the entire brain.

Acute Disease↗