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Biomedical subjects

M Siebler

Publications and source records attributed to M Siebler.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Effect of rhG-CSF on platelets using in vitro bleeding time and transcranial Doppler examination].

There is experimental evidence for recombinant human granulocyte colony-stimulating factor (rhG-CSF)-induced stimulation of hemostaseologic parameters including platelets. Using the closure time of the in vitro bleeding test (IVBT, Thrombostat 4000, VDG, Seeon) and different hemostaseologic parameters, our results are suggestive of a directly or indirectly induced in vivo stimulation of platelets following rhG-CSF stimulation in healthy stem cell donors. According to the negative transcranial Doppler microembolic monitoring of the middle cerebral artery, there is no evidence for clinically silent cerebral microembolism supporting a prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization.

Adolescent↗
PubMed1996

Color-flow Doppler-assisted duplex imaging fails to detect ulceration in high-grade internal carotid artery stenosis.

PURPOSE: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. METHODS: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (> or = 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. RESULTS: Interobserver reliabilities for detecting carotid plaque ulceration were kappa= 0.57 for ultrasonography and kappa = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomically defined ulceration (chi square = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). CONCLUSIONS: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions.

Adult↗
PubMed1996

Cerebrospinal fluid from multiple sclerosis patients inactivates neuronal Na+ current.

Multiple sclerosis is a common inflammatory disease of the CNS. A great number of immunologically active molecules have been identified in the CSF of these patients (CSF-MS), but the role of these substances in neuronal dysfunction, especially in the origin of transient symptoms, is unclear. Therefore, we investigated the effect of CSF from 13 multiple sclerosis patients on membrane currents of cultured cortical neurons from embryonic rat and compared it with the effect of CSF from 12 patients with non-inflammatory neurological diseases. We found an increase in Na+ current (INa) inactivation by a shift of the hoo curve to more hyperpolarizing potentials by 9.3 mV. This effect was reversible by washing and could be abolished by CSF-MS heat inactivation. The degree of the shift ranged from 4.3 mV to 17.6 mV and correlated with the IgG index, but not with the degree of pleocytosis, protein or albumin content. The maximal amplitude of INa was unchanged. We concluded that diffusible factors are released into the CSF which reduce neuronal excitability and thereby disturb the function of the neuronal network. These factors may well contribute to transient neurological symptoms seen in patients with "active' multiple sclerosis.

Adolescent↗
PubMed1996

Tumour necrosis factor-alpha increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells.

Tumour necrosis factor (TNF)-alpha, a strong immune mediator, is released within the brain during inflammatory diseases and contributes to immunological activation of glial cells. Here we report that, in astrocytes, TNF-alpha also affects the intracellular Ca2+ homeostasis and basic electrophysiological properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in a cell culture model, we found that TNF-alpha (10-1000 U ml-1), but not interleukin 1 or 6, induced a slow but more than two-fold increase of the intracellular Ca2+ concentration, which could be blocked by Co2+ (1.0 mM), verapamil (100 microM) or omission of external Ca2+. This intracellular Ca2+ increase was accompanied by a marked decrease of the membrane potential by 35 mV. CSF of patients with bacterial meningitis, known to contain large amounts of TNF-alpha, induced a similar depolarization of astrocytes, which was markedly reduced by a neutralizing anti-TNF-alpha antibody. We conclude that TNF-alpha induces an increase of intracellular Ca2+ and a depolarization in astrocytes with the consequence of disturbing voltage-dependent glial functions such as regulation of local ion concentrations and glutamate uptake. During inflammatory CNS diseases this immuno-electrical coupling may contribute to an impairment of neuronal function.

Animals↗
PubMed1996

How good is intercenter agreement in the identification of embolic signals in carotid artery disease?

BACKGROUND AND PURPOSE: There has been concern regarding the reproducibility of the detection of embolic signals, particularly in patients with carotid artery stenosis in whom the signals are of low intensity. No published studies have examined inter-center agreement in reporting specific embolic signals or the factors responsible for any lack of agreement. We examined reproducibility between two centers in which widely differing proportions of embolic signals have previously been reported in patients with carotid artery stenosis. METHODS: Recordings from the middle cerebral artery of eight patients with ipsilateral carotid artery stenosis in whom embolic signals had been detected during a previously study were independently examined by three experienced observers in one center and by one experienced observer in another center. We calculated agreement within and between centers by estimating the probability that one observer would identify a specific embolic signal if other observers had identified it (a probability of 1 indicates complete agreement). The influence of different characteristics of the embolic signal on the probability of its detection as an embolic signal was determined. RESULTS: A high level of agreement in the identification of specific embolic signals was found. This was similar between all observers (.90), between the three observers in one center (.89), and between observers in the two different centers (.94). The probability of detection was independently related to the relative intensity of the embolic signal (P<.0001). It was less (although significantly) independently related to the position of the embolic signal in the cardiac cycle (P=.02), with signals in systole being more reliably detected. There was no independent relationship between the probability of detection and either the duration of the embolic signal or the velocity at the maximum intensity increase. The use of threshold intensity as a criterion for embolic signal detection increased interobserver agreement but reduced the sensitivity in detecting signals. CONCLUSIONS: The high level of interobserver agreement suggests that the technique is sufficiently reproducible for clinical use.

Blood Flow Velocity↗
PubMed1995

Cerebral microembolism in patients with Sneddon's syndrome.

BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.

Adult↗
PubMed1995

Cooperative effects of neuronal ensembles.

Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons.

Animals↗
PubMed1995

Impairment of electrophysiological function of astrocytes by cerebrospinal fluid from a patient with Waldenström's macroglobulinemia.

Patients with the Bing Neel type of Waldenström's macroglobulinemia often present with global neurological symptoms. In this case report, we investigated the effects of cerebrospinal fluid (CSF) of a such a patients (CSF-WM), who presented with seizures and psychomotor slowing, on the electrophysiological properties of cultured rat neurons and astrocytes. Membrane potential and Na+ and K+ currents of neurons were unaffected. Astrocytes, however, were significantly depolarized from -77.6 +/- 8.2 mV to -48.0 +/- 7.6 mV (38%) by CSF-WM. The depolarization was markedly reduced after CSF-WM heat inactivation or after pre-incubation of astrocytes with dexamethasone (1 microM). Astrocytes are electrophysiologically active cells, which control local ionic micro-environment. Therefore, we conclude that global neurological symptoms in the Bing Neel type of Waldenström's macroglobulinemia like generalized seizures can result from an impairment of glial cells electrophysiological functions.

Aged↗
PubMed1995

Cerebral microembolism and the risk of ischemia in asymptomatic high-grade internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography distal to internal carotid artery stenosis occurs more frequently in recently symptomatic compared with asymptomatic patients. It has remained unclear whether cerebral microembolism also indicates a higher risk of future cerebral or retinal ischemia. SUMMARY OF REPORT: Sixty-four asymptomatic patients with unilateral 70% to 90% internal carotid artery stenosis were investigated prospectively (mean follow-up, 72 weeks). Five patients developed ischemic symptoms attributable to the stenosis (transient ischemic attack, 2 patients; stroke, 3 patients). A microembolic rate of > or = 2 per hour in the ipsilateral middle cerebral artery was associated with a substantially increased risk of developing ischemia of the corresponding carotid territory (odds ratio, 31; 95% confidence interval, 3 to 302; P = .005). CONCLUSIONS: This prospective pilot study suggests that cerebral microembolism detected with transcranial Doppler sonography may define a high-risk subgroup among patients with asymptomatic high-grade internal carotid artery stenosis.

Aged↗
PubMed1995

Plaque ulceration and lumen thrombus are the main sources of cerebral microemboli in high-grade internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Previous work has shown that rates of cerebral microemboli downstream of high-grade internal carotid artery stenosis are higher in recently symptomatic compared with asymptomatic patients. In addition, microembolic rates decline after carotid endarterectomy. We conducted a prospective investigation of 40 consecutive asymptomatic or recently symptomatic patients undergoing carotid endarterectomy for 70% to 95% internal carotid artery stenosis to determine the relationship between microembolic rate and pathoanatomic features of the carotid plaque. METHODS: Transcranial Doppler monitoring including automated emboli detection was performed preoperatively to assess the rate of cerebral microemboli of the ipsilateral middle cerebral artery. The corresponding endarterectomy specimens were evaluated histologically with respect to the occurrence of plaque fissuring, intraplaque hemorrhage, plaque ulceration, or intraluminal thrombosis. RESULTS: There were strong associations between plaque ulceration, intraluminal thrombosis, and downstream cerebral microemboli (P < or = .005, respectively). There were no correlations of microembolism with plaque fissuring or intraplaque hemorrhage (P = .82 and P = .28, respectively). CONCLUSIONS: We conclude that ulceration and luminal thrombosis of the atheromatous plaque are the main sources of downstream cerebral microemboli in patients with high-grade internal carotid artery stenosis. Our data support the view that these pathoanatomic features may also play a key role in symptom development.

Adult↗
PubMed1995

Cheyne-Stokes respiration in ischemic stroke.

We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute ischemic stroke. Seventeen (53%) had Cheyne-Stokes respiration with concomitant drops in oxygen saturation, unrelated to infarct location. The ventilatory disturbance promptly reversed after intravenous theophylline ethylenediamine or oxygen inhalation. The therapy is a simple way of improving arterial oxygenation in a large subgroup of patients with acute ischemic stroke.

Adult↗
PubMed1995

Variability of Doppler microembolic signal counts in patients with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. METHODS: From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. RESULTS: No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). CONCLUSIONS: The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart.

Cerebral Arteries↗
PubMed1994

Bacterial endotoxins impair electrophysiological properties of cultured astrocytes but not of cultured neurons.

The endotoxins of bacteria are lipopolysaccharides which are released in the central nervous system during bacterial meningitis. Endotoxin titers in cerebrospinal fluid correspond to the appearance of severe neurological symptoms like seizures and coma. The pathogenic mechanism, however, by which endotoxins disturb neuronal function, is unclear. The functional deficit may originate either from direct alteration of neuronal excitability or from indirect effects mediated by glial cells. Therefore, we investigated the effects of lipopolysaccharides on electrophysiological properties of cortical neurons and astrocytes in separate cell cultures. Membrane potential, resistance and membrane currents of neurons were unaffected. By contrast, astrocytes depolarized markedly in a dose dependent manner (concentration range 1.0-10.0 micrograms/ml). The depolarization was Na+ dependent and amiloride sensitive (250 microM), both indicating an activation of an electrogenic sodium dependent transport system like the Na+/Ca2+ exchanger as a source of the depolarization. These results suggest that endotoxin induced neurological deficits are not caused by direct effects on neurons, but may result from an impaired glial cell function.

Amiloride↗
PubMed1994

Lipopolysaccharides and leukotriene B4 induce independently regulated electrophysiological and immunological responses in cultured astrocytes.

Astrocytes play an important role in immunological processes within the central nervous system. They are able to produce cytokines like interleukin 6 (IL-6) and depolarize substantially after stimulation by lipopolysaccharides (LPS) or leukotriene B4 (LTB4). Therefore, we investigated the coupling between these immunological and electrophysiological processes. Amiloride (250 microM), a blocker of various Na+ transport systems, inhibited LPS (5 micrograms/ml)-induced depolarization, whereas the LPS-induced release of IL-6 was unaffected, indicating different intracellular regulatory mechanisms. LTB4 (1.0 microM) induced a depolarization of a similar degree but mediated by a different ionic mechanism and failed to induce a detectable IL-6 release. Dexamethasone (1.0 microM) and cycloheximide (2.0 microM) specifically reduced LTB4-induced depolarization, while LPS-induced depolarization was unaffected, providing further evidence for different regulatory pathways. Neither the depolarization nor the immunological stimuli served as a proliferation signal. These data demonstrate that independent immunological and electrophysiological responses with specific intracellular regulation are evoked after stimulation with LPS or LTB4. With respect to functional disturbance of depolarized glial cells, e.g. in maintaining local ionic homeostasis, neuronal excitability may be affected indirectly and by this way account for the appearance of neurological symptoms during inflammatory CNS diseases.

Animals↗
PubMed1994

Real-time identification of cerebral microemboli with US feature detection by a neural network.

PURPOSE: Abnormal transcranial Doppler ultrasonographic (US) signals indicating cerebral microembolism have characteristic but complex features. The authors wanted to assess the agreement among human observers and test the feasibility of an automated detection system. MATERIALS AND METHODS: Automated on-line detection of cerebral microemboli was accomplished by employing real-time overlapping Fourier transform and artificial neural network technology. By using long-term transcranial Doppler US recordings of the middle cerebral artery in consecutive cerebrovascular and cardiac patients, the method was evaluated in a clinical setting. RESULTS: The proportion of specific agreement (ps) among four experienced investigators identifying cerebral microemboli was high (mean ps, 0.91). Agreement among the neural network and the human observers was only slightly less (mean ps, 0.77). CONCLUSION: The technique allows highly reliable on-line evaluation of transcranial Doppler US recordings across multiple centers. It obviates time-consuming analyses by human observers.

Humans↗