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Biomedical subjects

M Hennerici

Publications and source records attributed to M Hennerici.

At least 73 records · Page 4Linked to original sources
PubMed1999

Fas (APO-1/CD95) in inflammatory CNS diseases: intrathecal release in bacterial meningitis.

Release of Fas (APO-1, CD95), a type L-membrane protein which plays a crucial role in cytokine-mediated apoptosis was investigated in bacterial meningitis, viral meningoencephalitis and multiple sclerosis in vivo. After correction for bloodbrain-CSF-disruption, significantly increased intrathecal release of Fas was demonstrated exclusively in bacterial meningitis arguing for an apoptotic cell death of granulocytes in the subarachnoidal space aimed to self-limit inflammatory host response.

Adolescent↗
PubMed1999

Modulation of striatal acetylcholine concentrations by NMDA and the competitive NMDA receptor-antagonist AP-5: an in vivo microdialysis study.

The effects of local perfusion with the competitive NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-methyl-D-aspartate (NMDA) on release of extracellular acetylcholine (ACh) and choline (Ch) in the dorsolateral striatum were studied using in vivo microdialysis in freely moving rats. AP-5 caused a dose-dependent decrease in ACh release that was counteracted by the addition of NMDA. Perfusion with AP-5 also decreased Ch levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(-5) M), but not high (10(-2) M and 10(-3) M) concentrations, that were associated with massive cellular death. These inhibitory effects of AP-5 and the stimulatory effect of NMDA in non-neurotoxic dosages on ACh release provide further evidence for a tonic stimulation of striatal cholinergic interneurons by glutamatergic neurons via NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1999

Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull.

Systemic thrombolysis of acute ischemic stroke with recombinant tissue plasminogen activator (rt-PA) has been established recently. Whereas the delay to and the rate of vessel recanalization are unknown, they are likely slower and smaller than for local application of rt-PA. This may contribute to the small benefits of recovery reported and stimulate further investigations to improve clot lysis. Pilot studies indicate that continuous-wave low-frequency ultrasound (US) can accelerate rt-PA-mediated recanalization of peripheral thrombotic vessel occlusion. For the hypothesized therapeutical purpose in stroke treatment, we measured the attenuation of ultrasound through the skull at different frequencies and intensities (33.3 and 71.4 kHz; 0.5 and 3.4 W/cm2), and investigated thrombolysis in vitro (n = 125 clots). Attenuation was lowest by transtemporal insonation of 33.3 kHz, 0.1 dB (0.9). Thrombolysis (artificial fibrin-rich clots) was significantly increased after 1 h (p < 0.025) and after 3 h (p < 0.01) for US treatment in combination with rt-PA vs. rt-PA alone. Results suggest that US increases rt-PA-mediated thrombolysis through the skull and may improve benefits of thrombolytic stroke treatment in vivo.

Brain Ischemia↗
PubMed1999

Comparison of transcranial Doppler flow velocity and cerebral blood flow during focal ischemia in rabbits.

The predictive value of transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) measurements for cerebral blood flow (CBF) calculations in humans is still controversial, and experimental correlative studies are lacking. The aim of the present study was to validate TCD signals of CBFV during focal cerebral ischemia. Therefore, CBFV determined in the middle cerebral artery (MCA) was compared with values of CBF obtained from autoradiograms of ischemic brain areas. To determine CBFV, a transcranial Doppler ultrasound probe (TCD) adapted to small sample volumes was used in 9 rabbits. CBF was quantified after a final infusion of [14C]-iodoantipyrine in the same animals. For focal cerebral ischemia induction, two threads were flushed upward simultaneously into the internal carotid artery, resulting in a flow reduction in the ipsilateral MCA. After thread occlusion, mean systolic CBFV in the MCA decreased from 49 +/- 9 cm/s to 22 +/- 3 cm/s. CBF in the caudate nucleus was reduced (19 +/- 8 mL/100 g/min) compared to the contralateral nonischemic side (52 +/- 18 mL/100 g/min). The decrease in hemispheric CBF correlated well with the decrease in both mean systolic (r = 0.97) and diastolic (r = 0.94) CBFV in the MCA (p < 0.01). The decrease in CBFV determined by transcranial Doppler ultrasound in the MCA appears to reflect the reduction in CBF in the affected brain hemisphere and can be used as a quantitative in vivo parameter for tissue perfusion.

Animals↗
PubMed1999

Clinical range and MRI in Creutzfeldt-Jakob disease with heterozygosity at codon 129 and prion protein type 2.

A 68 year old woman with sporadic Creutzfeldt-Jakob disease is described, who neither showed characteristic EEG abnormalities nor a positive test of the neuronal protein 14-3-3 or neuron specific enolase (NSE) in CSF, despite a clinical presentation with ataxia of cerebellar type, rapidly progressive dementia, myoclonus, and marked hyperintense signal abnormalities in the deep cortical layers and the basal ganglia on T2 and diffusion weighted MRI. Moreover she showed atypical clinical features with a syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) and a peripheral sensorimotor polyneuropathy. Whether these disturbances are independent of Creutzfeldt-Jakob disease or a feature of it is discussed. It has recently been shown that in Creutzfeldt-Jakob disease different clinical and pathological phenotypes correlate with the polymorphism at codon 129 of the prion protein gene (PRNP) and the type of the protease resistant fragment that accumulates in the brain. According to the new classification at least six sporadic variants of Creutzfeldt-Jakob disease exist. The molecular genetic analysis showed heterozygosity of PRNP at codon 129 for methionine and valine and the presence of PrP(CJD) type 2 in the brain of this patient. As a new feature of changes on MRI, striking cortical changes of hyperintense signals are described in diffusion weighted as well as T2 weighted MRI that directly correlate with the histomorphological spongy degeneration of the brain in this region. In cases of rapidly progressive dementia, Creutzfeldt-Jakob disease always needs to be considered even if unusual features are present and current diagnostic criteria are not in favour of this disease.

Aged↗
PubMed1999

Age and stimulus dependency of visually evoked cerebral blood flow responses.

BACKGROUND AND PURPOSE: During visual stimulation, the increased metabolic demand is coupled with an increase of cerebral blood flow velocity (pCBFV) in the posterior cerebral artery (PCA). Investigation of the visually evoked flow responses (VEFR, expressed as percentage of increase from baseline pCBFV values) was suggested for different conditions of vasoneuronal disorders in the absence of any systematic investigation in healthy subjects. METHODS: We investigated VEFRs from both PCAs to various increasingly complex paradigms (diffuse light, alternating checkerboard patterns, and a color video movie stimulation; 5, 10, 20, and 30-second intervals) in 60 healthy volunteers (mean age, 41.5+/-14.9 years; range, 24 to 80 years; 28 male, 32 female) at different recording sites (P1 versus P2 segments of PCAs). RESULTS: With increasing complexity of stimulation, the VEFRs increased significantly (24.3+/-10.3%, 28.5+/-13.5%, and 43.4+/-10.7%, respectively). Twenty-second stimulation intervals yielded maximal responses (41.5+/-13.2%) compared with 5-, 10-, and 30-second intervals (22.6+/-14.1%, P=0.001; 34.4+/-11.7%, P=0.0042; and 35.5+/-9.9%, P=0.0032, respectively). Significantly higher responses were gained from P2 segments than from P1 segments (42.7+/-7.2% versus 28.2+/-7.1%). Although VEFRs tended to decrease in amplitude with age (mean, 41. 7+/-10.5% [20 to 40 years], 35+/-9.2% [40 to 60 years], and 33.9+/-8.6% [60 to 80 years]); without significant sex-related differences, only the percentage decrement of the pulsatility indices during stimulation were significant (mean, 24+/-10.7% [20 to 40 years], 20+/-7.3% [40 to 60 years], and 13+/-11.2% [60 to 80 years]). CONCLUSIONS: For optimal stimulus conditions for maximum VEFRs, a colored video stimulation of 20-second intervals should be used to combine responses not only from the primary visual projection fields (V1 and V2) but also from temporal lobe areas (V3 through V5) often supplied by the PCA.

Adult↗
PubMed1999

Adhesion molecules in cerebrovascular diseases. Evidence for an inflammatory endothelial activation in cerebral large- and small-vessel disease.

BACKGROUND AND PURPOSE: Adhesion molecules mediate attachment and transendothelial migration of leukocytes as a critical step in pathogenesis of atherosclerosis. Their expression and release were comparatively investigated in patients with large- and small-vessel disease of the central nervous system. METHODS: With immunological methods, serum concentrations of endothelial-derived adhesion molecules (soluble endothelial-leukocyte adhesion molecule [sE-selectin], soluble vascular-leukocyte adhesion molecule-1, and soluble intercellular adhesion molecule-1 [sICAM-1]) were quantified in patients with obstructive disease of extracranial (n=89) and intracranial (n=20) large-vessel disease and patients with subcortical vascular encephalopathy (n=64), a cerebral small-vessel disease. As controls, age- and sex-matched subjects without obstructive cerebrovascular disease (n=67) were studied. RESULTS: We observed significantly increased serum concentrations of sE-selectin and sICAM-1 in patients with both obstructive disease of the large brain-supplying arteries and subcortical vascular encephalopathy. Interestingly, the highest levels were observed in intracranial macroangiopathy. Furthermore, concentrations of sICAM-1 and sE-selectin were significantly increased in current smokers but not in diabetic or hypertensive patients. CONCLUSIONS: The observation of elevated release of endothelial-derived adhesion molecules in both patients with stenoses of the large brain-supplying arteries and patients with subcortical vascular encephalopathy indicates that inflammatory endothelial activation and adhesion of leukocytes play similarly important roles in cerebral large- and small-vessel disease.

Aged↗
PubMed1999

Four-dimensional ultrasonographic characterization of plaque surface motion in patients with symptomatic and asymptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: In vitro studies of atherosclerotic plaque fracture mechanics suggest that analysis of local variations in surface deformability may provide information on relative vulnerability to plaque fissuring or rupture. We investigated plaque surface deformations in patients with symptomatic and asymptomatic carotid artery disease using 4-dimensional ultrasonography and techniques for measuring optical flow. METHODS: Four-dimensional ultrasound examinations of carotid artery plaques were performed in 23 asymptomatic and 22 symptomatic patients with 50% to 90% stenosis of the internal carotid artery. Plaque surface motion during 1 cardiac cycle was computed with a hierarchical model-based motion estimator. Results were compared with plaque echogenicity and surface structure. RESULTS: Of the 45 patients examined, plaque surface motion estimates were obtained for 18 asymptomatic and 13 symptomatic patients. There were no significant differences in echogenicity or surface structure of asymptomatic and symptomatic plaques (P>0.05). Results of motion estimation showed that asymptomatic plaques had surface motion vectors of equal orientation and magnitude to those of the internal carotid artery, whereas symptomatic plaques demonstrated evidence of inherent plaque movement. There was no significant difference in maximal plaque velocity between symptomatic and asymptomatic plaques (P<0.14). Maximal discrepant surface velocity (MDSV) in symptomatic plaques was 3.85+/-1.26 mm/s (mean+/-SD), which was significantly higher (P<0.001) than MDSV of asymptomatic plaques with 0.58+/-0.42 mm/s (mean+/-SD). CONCLUSIONS: ++MDSV of carotid artery plaques is significantly different in asymptomatic and symptomatic disease. Further studies are warranted to determine whether plaque surface motion patterns can identify vulnerable plaques in patients with carotid artery stenosis.

Aged↗
PubMed1999

Improving the outcome of acute stroke management.

Recent research into stroke mechanisms suggests that it may be possible to reduce mortality and improve functional outcome in stroke patients, provided clinicians act quickly and appropriately. In this article, standards for optimal stroke management with new therapeutic strategies aiming to restore cerebral blood flow and to protect brain neurons will be discussed.

Acute Disease↗
PubMed1999

Changes in coagulation and fibrinolysis markers in acute ischemic stroke treated with recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis and treatment of cerebral ischemia. In this study, we characterized the kinetics of hemostatic abnormalities induced by acute ischemic stroke and its thrombolytic (recombinant tissue plasminogen activator [rtPA]) or anticoagulant (heparin) treatment. METHODS: Systemic generation of molecular markers of hemostasis (fibrin monomer, D-dimer, thrombin-antithrombin complex, and fibrinopeptide 1.2) was monitored in acute ischemic stroke, and the effects of thrombolytic and anticoagulant treatments were analyzed. RESULTS: Thrombolysis with rtPA induced a massive response of markers of coagulation activation and fibrin formation that peaked after 1 to 3 hours and persisted for up to 72 hours. In contrast, only minor hemostatic changes were induced by acute ischemic stroke itself. Administration of heparin did not significantly affect these hemostatic abnormalities. CONCLUSIONS: This first characterization of the coagulation activation induced by rtPA treatment for acute ischemic stroke and the failure to abolish such hemostatic abnormalities by heparin may be of value for further refinement of the currently discussed thrombolytic therapy and the controversial adjunctive anticoagulant prophylaxis in stroke patients.

Aged↗
PubMed1998

Enhanced vulnerability to apoptotic cell death in sporadic Alzheimer's disease.

All important neuropathological features like neurodegeneration and amyloid deposition occur similarly in familial and in sporadic Alzheimer's disease (AD) patients, suggesting a common pathogenetic mechanism. We investigated whether defective vulnerabilty to the induction of the apoptotic cell death pathway might be one of the underlying mechanisms leading to progressive cell death in sporadic AD. Our test could prove useful in supporting the diagnosis of AD and in predicting individuals predisposed to AD.

Aged↗
PubMed1998

Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation.

OBJECTIVE: To investigate the association between affective and neuroendocrine abnormalities, commonly observed in multiple sclerosis, with inflammatory disease activity. DESIGN: Cross-sectional design. Twenty-three patients with definite relapsing-remitting multiple sclerosis and age- and sex-matched control subjects were investigated. Depression and anxiety were assessed using structured interviews, self-report measures, and Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria. Neurologic impairment was assessed by the Kurtzke Expanded Disability Status Scale and function of hypothalamic-adrenal-pituitary axis was analyzed using a corticotropin-releasing hormone stimulation test after dexamethasone suppression. Inflammatory disease activity was evaluated first by routine and experimental laboratory tests, and second by magnetic resonance assessment of gadolinium uptake of multiple sclerotic plaques. SETTING: University hospital, a major provider of acute neurologic care. RESULTS: Compared with controls, patients with multiple sclerosis had higher scores on depression and anxiety scales and exhibited a failure of suppression of cortisol release after dexamethasone pretreatment. Both affective symptoms and neuroendocrine abnormalities were correlated with cerebrospinal fluid white blood cell counts and presence of gadolinium-enhancing lesions on magnetic resonance images; however, no association with the degree of neurologic impairment was observed. CONCLUSION: Affective and neuroendocrine disorders were related to inflammatory disease activity but not to degree of disability, supporting the hypothesis that these symptoms are causally associated with brain injury.

Adult↗
PubMed1998

Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain-Barré syndrome.

BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of excessive alcohol consumption; however, acute axonal polyneuropathy related to alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data. RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had lost a substantial amount of weight recently. Additional clinical features included painful paresthesia, myalgia, and glove and stocking-type sensory loss. Repeated cerebrospinal fluid examinations failed to show the marked increase of protein concentration with normal cell count typical of Guillain-Barré syndrome, although the protein level was mildly elevated in 1 patient. Blood laboratory findings were consistent with longstanding alcohol abuse. Compound muscle and sensory nerve action potentials were absent or reduced, while conduction velocities were normal or mildly reduced. Three to 4 weeks after onset, needle electromyography displayed moderate to severe fibrillations and positive sharp waves in addition to normal motor unit potentials, indicating an acute axonal polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient. CONCLUSIONS: Excluding other factors, we assume that in these patients the combination of alcohol abuse and malnutrition caused severe acute axonal polyneuropathy. Its distinction from Guillain-Barré syndrome is important because treatment requires balanced diet, vitamin supplementation, and abstinence from alcohol, while immunotherapy may not be indicated.

Acute Disease↗
PubMed1998

Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke.

OBJECTIVE: To explore the relationship between hypoperfusion, embolism, and brain infarction. DESIGN: We studied 4 situations in which brain infarction is related to hypoperfusion: extracranial and intracranial occlusive vascular disease, reduced functional vascular reserve in patients with carotid artery occlusive disease, reduced collateral blood flow in patients given thrombolytic treatment, and cardiac surgery. We reviewed results of emboli monitoring using transcranial Doppler ultrasonography. RESULTS: Hypoperfusion is strongly linked to brain ischemia and infarction. The evidence includes close correlation of (1) the severity of arterial stenosis with brain infarction; (2) impaired functional blood flow reserve in patients with carotid artery disease and subsequent brain infarction; (3) reduced collateral blood flow with poor prognosis after thrombolysis; and (4) stroke-related neurologic deficits after cardiac surgery to hypoperfusion during surgery. Microembolization is common in patients with severe symptomatic carotid artery stenosis and during and after cardiac surgery. CONCLUSIONS: Hypoperfusion and embolism often coexist and their pathophysiological features are interactive. Arterial lumenal narrowing and endothelial abnormalities stimulate clot formation and subsequent embolization. Reduced perfusion limits the ability of the bloodstream to clear or wash out emboli and microemboli and reduces available blood flow to regions rendered ischemic by emboli that block supply arteries. The brain border zones are a favored destination for microemboli that are not cleared. We posit that impaired washout is an important but neglected concept that intertwines hypoperfusion, embolization, and brain infarction.

Arterial Occlusive Diseases↗
PubMed1998

Adhesion molecules in tissue injury: kinetics of expression and shedding and association with cytokine release in humans.

Adhesion molecules are responsible for leukocyte recruitment in injured tissues. Here, the kinetics of expression and shedding of endothelial (sE-selectin-1, sP-selectin, and sICAM-1) and neutrophil (CD11b, CD62L, and CD54) adhesion molecules was investigated by serial determinations of serum concentrations in 20 patients with elective hip arthroplasty as an exemplary condition of acute inflammation in humans. Changes were related to secretion of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNF-alpha) as their possible inducing signals. sE-selectin-1 responded to injury with a significant increase in concentrations already after 20 min, followed by sP-selectin and sICAM-1, which increased at Hour 10 and Day 1. Expression of CD11b and CD62L acutely responded to injury (within 1 h) by a parallel increase and decrease, respectively, and normalized by Day 1. Increases in concentrations of IL-1beta and TNF-alpha preceded the increase in adhesion molecules and significantly correlated with the response of sE-selectin-1 and sICAM-1. In conclusion, the close associations between release of IL-1beta and TNF-alpha and sE-selectin and sICAM-1 shown in this kinetic study indicates a key role of these cytokines in upregulation of endothelial rather than neutrophil adhesion molecules in vivo.

Aged↗
PubMed1998

Changes of intracellular calcium regulation in Alzheimer's disease and vascular dementia.

Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients. However, the findings are still controversial. Using blood lymphocytes and neutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD patients and non-demented controls. We found no major difference in Ca2+ homeostasis, since neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation indicating an impaired function of Ca2+ influx-controlling mechanisms. Furthermore, we studied whether differences exist in Ca2+ regulation between lymphocytes from patients with vascular dementia and AD patients, to define AD-specific alterations and to distinguish between the two dementia groups and non-demented control subjects respectively. First evidences indicate that Ca2+ mobilization in lymphocytes is specifically impaired in lymphocytes from patients with vascular dementia.

Aged↗