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Biomedical subjects

M Siebler

Publications and source records attributed to M Siebler.

At least 73 records · Page 4Linked to original sources
PubMed1994

Usefulness of an intravenous contrast medium in the characterization of high-grade internal carotid stenosis with color Doppler-assisted duplex imaging.

BACKGROUND AND PURPOSE: The remaining limitations of ultrasonographic imaging in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion may be overcome by enhancing the echogenicity of flowing arterial blood with contrast agents. This study assessed the usefulness of the intravenous (transpulmonary) contrast medium SH U 508 A in improving the characterization and quantification of severe internal carotid stenosis. METHODS: We examined 32 patients (30 had vessels with a stenosis of greater than 70% luminal narrowing and 2 had vessel occlusions) using a 7.5-MHz linear-array transducer for color Doppler-assisted duplex imaging before and after injection of the contrast medium. RESULTS: The SH U 508 A-induced increase in carotid blood echogenicity began 11 +/- 2 (mean +/- SD) seconds after the start of the bolus injection, peaked at 21 +/- 2 dB, and showed a half-life of 75 seconds. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length, respectively) obtained before and after contrast application were highly correlated (r > .90). Visualization of the entire length of the intrastenotic residual flow lumen, however, was significantly improved by contrast enhancement (52% versus 83%, P = .01). CONCLUSIONS: This pilot study on patients with extracranial carotid artery disease suggested that ultrasonic contrast media may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.

Aged↗
PubMed1994

Cerebral microembolism in symptomatic and asymptomatic high-grade internal carotid artery stenosis.

Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (> or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (< 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate > or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of "unstable ICA disease."

Aged↗
PubMed1993

Impaired neuronal function induced by the immune mediator leukotriene B4.

Inflammatory cerebral processes, mediated by immunologically active substances or invading of macrophages are frequently associated with neuronal dysfunction. This study describes the effects of leukotriene B4 on membrane potential, membrane resistance and potassium currents of cultured cortical neurons from the embryonic rat. Leukotriene B4 (1 microM) did not depolarize cortical neurons but induced a reversible reduction of voltage-dependent potassium outward currents (IK) in a subpopulation of these cells (35%). The results suggest that, in comparison to astrocytes, cortical neurons lack receptors for LTB4 or its intracellular activation pathway. Immune mediators, such as leukotrienes, may contribute to neuronal dysfunction during inflammatory diseases by affecting neuronal membrane currents.

Animals↗
PubMed1993

Strychnine-sensitive glycine receptors in cultured primary neurons from rat neocortex.

After 1 day in vitro (DIV) glycine (1 mM) evoked chloride-dependent membrane currents in about 50% of primary cultured rat neocortical neurons and more than 98% of the cells were glycine-sensitive after 2 DIV lasting for at least up to 12 DIV which was similar to GABA chemosensitivity. Strychnine (IC50 40 nM) and picrotoxin (30 microM) but not bicuculline (50 microM) blocked the glycine-evoked currents. The results provide evidence for a very early expression of glycine receptors on cortical neurons leading to a powerful chloride channel-operating capacity during early development.

Animals↗
PubMed1993

Depolarization of cultured astrocytes by leukotriene B4. Evidence for the induction of a K+ conductance inhibitor.

Since astrocytes have been shown to participate in intracerebral immunological processes we investigated the effect of the immune mediators, leukotrienes (LT) B4, LTC4 and LTD4 on membrane properties of cultured astrocytes from neonatal rat brain. When LTB4 was added to the bath solution the membrane potential slowly decreased from -96 mV to -38 mV. While LTB4 at a concentration of 500 nM was ineffective, depolarization occurred when concentrations of 750 nM and above were used. The depolarizing effect was specific for LTB4, since LTC4 and LTD4, other arachidonic acid derivates, failed to depolarize astrocytes at even higher concentrations (1 microM). When the K+ conductance blocker, Ba2+ (2 mM), was added to the bath solution, astrocytes depolarized to the same degree but no further depolarization was achieved when LTB4 was added. Bath application of Co2+ (1 mM), in order to reduce putative Ca2+ inward currents or reduced internal chloride concentration, did not alter the LTB4-induced depolarization, thus arguing against additional Ca(2+)- or Cl(-)-dependent depolarizing effects. The LTB4-induced depolarization could be markedly reduced, however, by preincubation of the cells with cycloheximide (2 microM), which blocks translation and thereby protein synthesis. Cycloheximide alone had no effect on the membrane potential. These data indicate that, in astrocytes, LTB4 stimulates the synthesis of a protein, which, in turn, inhibits K+ conductances. This effect could impair glial, as well as neuronal, functions during CNS diseases accompanied by immunological processes.

Animals↗
PubMed1993

Spontaneous activity and recurrent inhibition in cultured hippocampal networks.

As a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium-dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), "miniature" PSPs and APs appeared after 3-6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid-shaped neurons could be identified after 10-12 DIV, which fired preferentially at interspike intervals between 20-120 ms and 190-400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA-A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA-ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is network-driven, based on synaptic "noise" and patterned by recurrent inhibition.

Action Potentials↗
PubMed1993

Paroxysmal long-lasting depolarizations in cultured hippocampal neurons are generated by activation of NMDA and non-NMDA receptors.

In primary cultures of hippocampal neurons from the embryonic rat, spontaneous depolarizations lasting up to 6 sec and resembling paroxysmal depolarization shifts (PDSs) appeared after 11 days in vitro. These depolarizations are presumably generated by synaptic events, because: (1) both their appearance and duration are independent of membrane potential, (2) the amplitudes of the underlying currents depend monotonically on membrane potential, and (3) they are reversed at the reversal potential of the excitatory postsynaptic potentials (EPSPs). In addition, PDSs disappeared reversibly when sodium-dependent action potentials were blocked by tetrodotoxin (10 microM) and when synaptic transmission was reduced by elevated Mg2+ (5 mM). Further, the fact that these depolarizations can appear simultaneously in two neurons in paired recordings also points to a synaptic origin. Inhibition of glutaminergic synaptic transmission by kynurenic acid (50 microM) and the NMDA-antagonist D-2-amino-5-phosphonovaleric acid (APV; 50 microM) led to a marked shortening of the depolarizations. This blocking effect of kynurenic acid and APV and comparison with the currents elicited by locally applied glutamate or NMDA provide evidence for an activation of both types of glutamate receptors to induce PDSs. The role of alteration of glutaminergic synaptic transmission in the induction and maintenance of these depolarizations is discussed in the context of results from the literature on the appearance of PDSs in cultures grown under chronic blockade of glutamate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1993

Silent cerebral embolism caused by neurologically symptomatic high-grade carotid stenosis. Event rates before and after carotid endarterectomy.

Fourteen symptomatic patients with severe extracranial internal carotid artery stenosis (> or = 70% of luminal narrowing) were monitored using long-term transcranial Doppler ultrasonography to determine the rate of clinically silent embolism of the ipsilateral middle cerebral artery. Before carotid endarterectomy (all patients being treated with intravenous heparin), 462 such events occurred during a total monitoring time of 45 h. Statistical analyses of the inter-event intervals and of the relationship between events and cardiac cycle revealed random occurrence. While the ipsilateral events were found in each subject, silent embolism of the contralateral middle cerebral artery occurred in only four patients each of whom had angiographically proven intracranial cross-flow from the symptomatic carotid territory (39 embolic events during 7 h monitoring time). The other 10 patients showed no contralateral embolism (10 h monitoring time). Five or more days (median 10 days) after surgery and cessation of intravenous anticoagulation the ipsilateral event rate had dropped to 13 in 33 h (P < 0.001) and the contralateral rate to zero. This suggests that the stenosed arterial segment is the main source of cerebral embolism detectable with ultrasound in symptomatic patients with high-grade internal carotid stenosis, and that carotid endarterectomy substantially reduces the rate of these events. Since reduction of ipsilateral stroke risk by successful endarterectomy is known to be of a similar degree in patients as those studied here, transcranially detected embolism may represent a new marker of disease activity of extracranial carotid artery stenosis.

Adult↗
PubMed1993

Between-method correlation in quantifying internal carotid stenosis.

BACKGROUND AND PURPOSE: The degree of internal carotid stenosis has emerged as the most important predictor of ischemic stroke in extracranial carotid artery disease. The purpose of this study was to assess the validity of the noninvasive techniques for quantifying internal carotid stenosis with respect to the accepted standard of intra-arterial angiography. METHODS: We measured the maximum percentage reduction in luminal diameter on the intra-arterial digital subtraction angiograms of 56 symptomatic patients with extracranial internal carotid stenosis (n = 77) or occlusion (n = 20). These data were compared with independent measurements based on continuous-wave Doppler ultrasonography, pulsed-wave Doppler spectrum analysis, color Doppler-assisted duplex imaging, and magnetic resonance angiography. RESULTS: Correlations with intra-arterial angiography were equally strong (r > .90) for magnetic resonance angiography, continuous-wave Doppler, and color duplex analysis. Positive and negative predictive values for (therapeutically relevant) 70% to 99% stenosis were higher for continuous-wave Doppler (.82, .97) and color duplex (.84, .98) than for magnetic resonance angiography (.79, .81). Also, accuracy in quantifying high-grade stenosis was better for both of these ultrasonographic techniques, mainly due to the frequent occurrence of a "flow gap" on the magnetic resonance angiograms. Continuous-wave Doppler and magnetic resonance angiography, but not color duplex, failed to detect slow residual arterial flow in one and two cases of symptomatic "pseudo-occlusion" of the internal carotid, respectively. CONCLUSIONS: (1) Several noninvasive methods compare well with intra-arterial angiography in identifying and quantifying high-grade internal carotid stenosis; (2) the use of these noninvasive methods may suffice for treatment decisions; and (3) because residual between-method disagreement is partly explained by principles of physics, the validity of continuous-wave Doppler and color duplex in quantifying 60% to 99% stenosis is likely to be underestimated by correlation with intra-arterial angiography.

Blood Flow Velocity↗
PubMed1993

Cerebral hemodynamics in obstructive sleep apnea.

We have investigated cerebral blood flow velocity (CBVF) in 14 patients with marked obstructive sleep apnea syndrome using transcranial Doppler ultrasonography during sleep. The CBFV increased during apnea, with a mean acceleration of 0.9 cm/s2, followed by a rapid decrease during snoring. The same effect was obtained by voluntary apnea in healthy subjects, showing a smaller acceleration rate (0.6 cm/s2). These results provide evidence for a normal CO2 regulation of cerebral vessels during sleep apnea and do not support the notion of cerebral hypoperfusion during sleep being a risk factor for stroke.

Apnea↗
PubMed1992

An improved graphical method for pattern recognition from spike trains of spontaneously active neurons.

Spontaneous activity and rhythmical oscillations are common features of large neuronal networks in mammals. Detection of repetitive spike patterns or pacemaker activity during electrophysiological recording of spontaneous action potentials from single neurons can be difficult if a "noisy" background is present. This paper describes an improved method for an online spike train analysis based on joint interval histograms (JIH, Rodiek et al. 1962). By means of higher ordered JIH the discrimination of spike patterns with repetitive bursting activity or oscillations is possible even when randomly distributed action potentials appear. Examples of simulated spike trains and those recorded from cultured hippocampal neurons are presented.

Animals↗
PubMed1992

Detection of intracranial emboli in patients with symptomatic extracranial carotid artery disease.

BACKGROUND AND PURPOSE: Cerebral embolism from extracranial sources is an important cause of ischemic stroke. The purpose of this limited study using long-term transcranial Doppler ultrasonographic monitoring was to estimate the frequency of clinically silent intracranial embolisms in patients with symptomatic extracranial carotid artery disease. SUMMARY OF REPORT: By means of a 2-MHz pulsed-wave transcranial Doppler instrumentation, three consecutive patients with extracranial internal carotid artery stenosis (n = 2) or occlusion (n = 1) and recurrent ipsilateral ischemic events were monitored (19 hours total recording time). In addition, 10 control subjects without cerebrovascular disease were studied (25 hours total recording time). Formed-element emboli were defined as distinct signals within the fast Fourier-transform Doppler spectrum that were < 70 msec in duration and > 9dB greater in intensity than the background signal. Clinically silent formed-element embolism of ophthalmic or cerebral arteries was demonstrated in all three patients. Embolic events occurred only in the territory of the symptomatic internal carotid artery. The average rate of cerebral embolization at transcranial Doppler ultrasonography was 4.1/hr, with a mean signal duration of 47 msec. No emboli were found in control subjects. CONCLUSIONS: The observed high frequency of silent embolism of the intracranial arteries detected by transcranial Doppler monitoring in patients with recurrently symptomatic extracranial carotid artery disease should encourage studies of the prognostic and therapeutic implications of this method.

Adult↗
PubMed1991

[The leukostasis syndrome with a cerebral infarct in rapidly progressing chronic lymphatic leukemia].

An 82-year-old woman developed acute neuropsychiatric signs (confusion, disorders of speech and vision) together with ataxic gait and left hemiparesis mainly affecting the lower limb. For 10 years she had been known to have chronic lymphatic leukaemia (CLL) which had not hitherto needed treatment. The patient had an exceptionally high leucocyte count (1,300,000/microliters), most of the cells being morphologically atypical lymphocytes. The computed tomogram of the skull showed a marginal zone infarct with a hypodense focus in the area of the right middle and posterior cerebral arteries, extending from the cortical to subcortical zones almost as far as the posterior horn. This was interpreted as a leukostasis syndrome with cerebral infarction due to rapid progression of the CLL. Significant reduction of leucocyte count with considerable improvement in clinical signs was achieved after three doses of vincristine and prednisone together with one cycle of COP (cyclophosphamide, vincristine, prednisone) therapy. Although the leucocyte count is not an important criterion in planning the therapy of CLL, in the event of rapidly increasing leucocytosis it is important to begin cytoreductive treatment in good time so as to avert the leukostasis syndrome.

Aged↗
PubMed1990

Electrophysiological properties of rat septal region neurons during development in culture.

We report on the development of membrane properties of septal region neurons from embryonic rats in serum-free culture during 1-25 days in vitro (DIV). Na(+)-dependent action potentials could be evoked within 1 day after plating and 3 different types of outward current were observed by means of the patch-clamp technique: IK, IA and IC. In some neurons the neurotransmitter GABA evoked a chloride current after 2 DIV. In addition a cationic current elicited by glutamate appeared after 4 DIV. Within 8-12 DIV virtually all neurons were sensitive to both GABA and glutamate. Spontaneous action potentials and postsynaptic potentials occurred after 7-10 DIV but cultured septal neurons did not generate any pacemaker-like activity.

Action Potentials↗
PubMed1990

GABA and glutamate receptor development of cultured neurons from rat hippocampus, septal region, and neocortex.

The early development of functionally active GABA and glutamate receptors on neurons from hippocampus, septal region, and neocortex of embryonic rats were studied using primary dissociated serum-free cell cultures. The responses to GABA and glutamate, applied to individual neurons by pressure ejection, were tested at different developmental stages, starting at 1 day in vitro (DIV) until 3 weeks. In all three types of neuronal cultures, the GABAA-receptor developed prior to the glutamate receptors, and after 9 DIV most of the neurons were sensitive to both GABA and glutamate. N-methyl-D-aspartate (NMDA) and non-NMDA receptor subtypes of the glutamate receptors could be distinguished in hippocampal cultures. The development of GABA and glutamate receptors on septal region neurons appeared to be delayed as compared to hippocampal neurons. In neocortical cultures the majority of neurons was sensitive to GABA just after plating, whereas the sensitivity to glutamate was retarded. The differences in GABA and glutamate receptor development among these three neuronal cultures provide evidence that the appearance of transmitter receptors on cultured neurons is predominantly determined by intrinsic mechanisms rather than by environmental conditions. The proportion of spontaneously active networks in these cultures increased with a time course very similar to the rise in glutamate-sensitive neurons suggesting that functional active glutamate receptors may be involved in the generation of spontaneous activity.

Animals↗
PubMed1990

Cerebral blood flow velocity alterations during obstructive sleep apnea syndrome.

We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night.

Blood Flow Velocity↗
PubMed1988

GABA activated chloride currents in cultured rat hippocampal and septal region neurons can be inhibited by curare and atropine.

In order to study the influence of curare and atropine on the gamma-aminobutyric acid (GABA)-evoked chloride current, we have investigated cultures of hippocampal and septal region neurons from embryonic rats (E18). The neurons were cultured under the trophic influence of spatially separated astrocytes in serum-free medium. By means of the patch clamp technique, the excitable cells displayed GABA induced chloride currents within 1-15 days in vitro. In both cultures picrotoxin or bicuculline as well as curare or atropine reversibly inhibited the chloride current in a dose dependent manner. We conclude that curare and atropine are not specifically anti-cholinergic for cultured central neurons. Our results provide evidence for common ligand binding properties shared by GABAA and acetylcholine (ACh) receptors supporting the recent concept of a receptor superfamily.

Animals↗