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Biomedical subjects

E Bernd Ringelstein

Publications and source records attributed to E Bernd Ringelstein.

At least 19 recordsLinked to original sources
PubMed2006

The glu298asp polymorphism in the nitric oxide synthase 3 gene is associated with the risk of ischemic stroke in two large independent case-control studies.

The search for genes involved in the pathogenesis of stroke has been highlighted as a field of needs. We followed the concept, that stroke represents a complex genetic disorder, and analyzed the contribution of 106 informative single nucleotide polymorphisms (SNPs) from 63 candidate genes for cardiovascular diseases for the risk of stroke. We conducted two independent case-control studies in two different German regions and recruited a total of 1,901 hospitalized stroke cases and 1,747 regional population controls. The smaller of both studies was used as the replication study. Multiplex PCR in combination with allele-specific hybridization was used for genotype determination. Descriptive statistics, permutations and multivariable logistic regression were used in the analyses. After permutation testing 5 SNPs, located in the nitric oxide synthase 3, the alpha 2 integrin, the interleukin 13, the selectin P and the chemokine receptor 2 genes, had a significant allele difference between cases and controls in the larger study. For one of these SNPs, the glu298asp polymorphism in the nitric oxide synthase 3 gene, an association with ischemic stroke was replicated in the second study and also in a combined analysis of both studies. This association was independent of age, gender, hypertension, diabetes and hypercholesterolemia in both studies. Using large sample sizes and a replication study approach, we found evidence for a role of a polymorphism in the nitric oxide synthase 3 gene in stroke onset.

Aged↗
PubMed2006

Neuroleptic-induced dysphagia: case report and literature review.

Neuroleptic medication may cause extrapyramidal symptoms (EPS) that can affect swallowing as well. This report describes a case of drug-induced dysphagia in a 53-year-old man receiving haloperidol for treatment of schizophrenia. The diagnosis was established by fiberoptic endoscopic evaluation of swallowing. After changing medication to fluphenazin, dysphagic symptoms resolved. The literature on EPS-related dysphagia, its demographic features, typical symptoms, diagnostic modalities, clinical course, and treatment options is reviewed.

Antipsychotic Agents↗
PubMed2006

Treatment for obstructive sleep apnoea: effect on peripheral nerve function.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is suggested to be associated with peripheral nerve damage. A case-control study was conducted to provide further support to this observation. In a longitudinal intervention study, it was examined whether treatment for OSA has a possible beneficial effect on peripheral nerve function. METHODS: Participants were 23 patients with OSA and 23 controls matched for age and body mass index (BMI), all without any known cause of peripheral nerve damage. The sensory nerve action potential (SNAP) amplitudes of both sural nerves were determined. After 6 months of treatment for OSA, treatment compliance was evaluated and nerve conduction studies were repeated. RESULTS: Patients with OSA had significantly lower mean (standard deviation) sural SNAP amplitudes than controls (6.3 (3.5) v 11.2 (5.0), p < 0.001). Multivariate regression analysis including the variables age, BMI and Apnoea-Hypopnea Index (AHI) showed that both age (p < 0.01) and AHI (p < 0.05) were inversely related to the SNAP amplitude. On follow-up, the sural SNAP showed an increase of 2.6 mV on average (p < 0.001). Multivariate regression analysis including the variables age, BMI, AHI, pretreatment SNAP and treatment compliance identified only treatment compliance as being significantly related to the SNAP increase (p < or = 0.005). CONCLUSION: OSA is an independent risk factor for axonal dysfunction of peripheral sensory nerves. Impaired neural function is at least partly reversible with treatment for sleep apnoea.

Action Potentials↗
PubMed2006

CT angiography in acute stroke: does it provide additional information on occurrence of infarction and functional outcome after 3 months?

OBJECTIVE: To investigate whether acute phase intracranial CT angiography (CTA) independently predicts infarction and functional outcome in ischemic stroke. METHODS: Hundred and fifty-one consecutive patients with acute (<12 h) ischemic stroke who received intracranial CTA were investigated. Stroke severity on admission was determined using the National Institute of Health Stroke Scale (NIHSS). Reconstructed CTAs were investigated for relevant pathology. Follow-up imaging was performed 24-48 h after admission. Functional outcome was assessed after 3 months using the modified Rankin scale. Single factor and multiple logistic regression analyses were performed to predict infarction and dependency (modified Rankin scale > or = 3) on follow-up. RESULTS: Median NIHSS on admission was 10 (IQR 3-14). Out of the 151 patients, 61 (40%) had pathological CTA findings. Infarction was demonstrated in 60/61 patients (98%) with and in 67/90 patients (74%) without vessel pathology. Presence of infarction on follow-up imaging and dependency at 3 months were correlated with pathological CTA findings on admission in single factor analysis (each p < 0.001). After adjustment for age (> or =/<65 years), NIHSS (> or =/<10), sex, therapy, and time to presentation (> or =/<3 h), only NIHSS > or = 10 on admission was predictive of dependency at follow-up (p < 0.001). CONCLUSIONS: Pathological CTA findings in the acute phase of ischemic stroke do not independently predict a poor outcome at 3 months after acute stroke.

Acute Disease↗
PubMed2006

Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression.

Oncostatin M has been characterized as a potent growth inhibitor for various tumor cells. Oncostatin M-treated glioblastoma cells cease proliferation and instigate astrocytal differentiation. The oncostatin M-induced cell cycle arrest in G(1) phase is characterized by increased level of the cyclin-dependent kinase (CDK) inhibitory proteins p21(Cip1/Waf1/Sdi1) and p27(Kip1). Induction of p21 protein corresponds to increased mRNA level, whereas p27 accumulates due to increased stability of the protein. Interestingly, stabilization of p27(Kip1) occurs even in S phase, showing that p27 stabilization is a direct consequence of oncostatin M signaling and not a result of the cell cycle arrest. Degradation of p27 in late G(1) and S phase is initiated by the ubiquitin ligase complex SCF-Skp2/Cks1. Oncostatin M inhibits expression of two components of this E3 ligase complex (Skp2 and Cks1). Although combined overexpression of Skp2 and Cks1 rescues p27 degradation in S phase, it can not override p27 accumulation in G(1) phase and cell cycle arrest by oncostatin M. In addition to increasing Cdk inhibitor level, oncostatin M also impairs cyclin A expression. Cyclin A mRNA and protein level decline shortly after oncostatin M addition. The accumulation of two CDK inhibitor proteins and the repression of cyclin A expression may explain the broad and potent antiproliferative effect of the cytokine.

Antineoplastic Agents↗
PubMed2006

Toward a multimodal neuroprotective treatment of stroke.

BACKGROUND AND PURPOSE: Stroke remains a common medical problem with importance attributable to the demographic changes in industrialized societies. SUMMARY OF REVIEW: After years of setbacks, acute stroke therapy has finally emerged, including thrombolysis with tissue plasminogen activator (t-PA). However, t-PA treatment is limited by a narrow time window and side effects, so that only 3% of all stroke patients receive thrombolysis. Unimodal targeting of key events in stroke pathophysiology was not effective in providing long-term benefits, leading to negative results in previous clinical neuroprotective stroke trials. A successful future stroke therapy should approach multiple pathophysiological mechanisms besides revascularization at once, including reduction of t-PA-related side effects, prevention of cell death, stimulation of neuroregeneration, and plasticity. CONCLUSIONS: Strategies targeting these processes include multiple combination therapies as well as treatment with multimodal drugs that interact with these mechanisms. Here, we review such combination approaches, and outline how this concept could be developed into future stroke treatment.

Animals↗
PubMed2006

The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial.

BACKGROUND AND PURPOSE: The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. METHODS: As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps+/-values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator). RESULTS: For the reference tape, the cumulative ps+/-value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative rho=0.84; P<0.001). CONCLUSIONS: Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.

Aspirin↗
PubMed2006

Spontaneous acute dissection of the internal carotid artery: high-resolution magnetic resonance imaging at 3.0 tesla with a dedicated surface coil.

PURPOSE: Magnetic Resonance Imaging (MRI) has become the method of choice in the evaluation of patients with suspected cervical artery dissection (CAD). However, reliable identification of acute CAD might be impaired by the limited spatial resolution of standard 1.5 T MRI. In this preliminary study, we implemented a multicontrast high-resolution noninvasive vessel wall imaging approach at 3.0 T in patients with spontaneous CAD. METHODS AND MATERIALS: Ten patients with CAD of the internal carotid artery (ICA) were included in the study. 3.0 T MRI (Gyroscan Intera, Philips) was acquired using a dedicated phased-array coil. MRI-protocol consisted of: (1) bright blood 3D inflow MRA (TR/TE/FA = 25 milliseconds/3.1 millisecond/16 degrees , 120 slices, reconstructed voxel size 0.3 x 0.3 x 0.8 mm); (2) black blood cardiac-gated water-selective T1w 3D spoiled GE (TR/TE/FA = 31 milliseconds/7.7 milliseconds/15 degrees , 36 slices, 0.3 x 0.3 x 1.0 mm); and (3) black blood cardiac triggered fat suppressed T2w TSE (TR/TE/ETL = 3 heart beats/44 milliseconds/7, 18 slices, 0.3 x 0.3 x 2 mm). Three observers in consensus performed image analysis. Special attention was paid to the integrity of the luminal and adventitial vessel boundary and the presence of a communicating intimal tear or flap. RESULTS: 3.0 T MRI provided excellent delineation of vessel lumen and vessel wall as a result of the nearly complete suppression of arterial blood signal. An intramural hematoma could be identified in all patients, confined between the luminal and adventitial vessel boundary. In no patient a communicating intimal tear could be identified. Clear distinction between intramural hematoma and thrombus was possible. CONCLUSION: High-resolution vessel wall imaging in patients with acute CAD is feasible. The increased signal-to-noise ratio at 3.0 T can be invested to obtain a higher spatial resolution, permitting depiction of intimal and adventitial vessel wall boundary and the intramural hematoma in the diseased vessel segment. The morphologic information that is gained is helpful in the understanding of the underlying pathomechanismen of CAD.

Adult↗
PubMed2006

Cerebral small vessel diseases: manifestations in young women.

PURPOSE OF REVIEW: Cerebral small vessel diseases are responsible for 20-30% of ischemic strokes as well as for a considerable proportion of cerebral hemorrhages and encephalopathies. Less known than the manifestations in old age are those in young women comprising posterior encephalopathy and Susac's syndrome. RECENT FINDINGS: Magnetic resonance imaging has allowed us to identify posterior encephalopathy, characterized by headache, seizures, visual disturbances and hypertension, as a frequent complication of preeclampsia/eclampsia syndrome in the perinatal and postpartum period. Magnetic resonance findings are pathognomonic with bilateral cortical-subcortical lesions in the posterior hemispheres typically sparing the calcarine fissure. Conversely, white matter lesions on magnetic resonance imaging particularly involving the corpus callosum, and a (subclinical) sensorineural hearing loss are diagnostic of the retinocochleocerebral vasculopathy called Susac's syndrome. SUMMARY: Posterior encephalopathy can also follow from a broad spectrum of endotheliotoxic conditions like chemotherapy, immunosuppression and sepsis. Early recognition of the disorder is decisive for a benign outcome since therapy consists of removal of precipitating factors, lowering of blood pressure and treatment with magnesium sulfate. The retinocochleocerebral vasculopathy appears to be underdiagnosed. An autoimmune-mediated arteriolopathy is presumed and the disease is nearly always monophasic. A variety of therapeutic approaches have been recommended, none of which, however, is based on anything other than anecdotal evidence.

Adult↗
PubMed2005

Mutations in SEPT9 cause hereditary neuralgic amyotrophy.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis.

Amino Acid Sequence↗
PubMed2005

Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice.

Activated microglia and hematogenous macrophages are known to be involved in infarct development after cerebral ischemia. Traditionally, hematogenic macrophages are thought to be the primary cells to remove the ischemic cell debris. However, phagocytosis is a well known property also of activated microglia. Due to a lack of discriminating cellular markers, the cellular origin of phagocytes and the temporal course of phagocytosis by these two cell types are largely unknown. In this study, we used green fluorescent protein (GFP) transgenic bone marrow chimeric mice and semithin serial sections after methyl methacrylate embedding of the brains to dissect in detail the proportion of identified activated resident microglial cells and infiltrating hematogenous macrophages in phagocytosing neuronal cell debris after 30 min of transient focal cerebral ischemia. Already at day one after reperfusion, we found a rapid decrease of neurons in the ischemic tissue reaching minimum numbers at day seven. Resident GFP-negative microglial cells rapidly became activated at day one and started to phagocytose neuronal material. By contrast, hematogenous macrophages incorporating neuronal cell debris were observed in the ischemic area not earlier than on day four. Quantitative analysis showed maximum numbers of phagocytes of local origin within 2 days and of blood-borne macrophages on day four. The majority of phagocytes in the infarct area were derived from local microglia, preceding and predominating over phagocytes of hematogenous origin. This recruitment reveals a remarkable predominance of local defense mechanisms for tissue clearance over immune cells arriving from the blood after ischemic damage.

Animals↗
PubMed2005

Benefit of echocontrast-enhanced transcranial arterial color-coded duplex ultrasound.

OBJECTIVES: Proper assessment of the intracranial arteries by transcranial color-coded duplex sonography (TCCD) is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all. MATERIAL AND METHODS: We investigated 67 temporal windows of 47 patients with insufficient native transtemporal insonation conditions before and after the application of the second-generation (gas-filled) microbubble contrast agent Sonovue (in 20 patients out of these 47, both temporal windows were insufficient, in the remaining 27 only one side). RESULTS: As compared to the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (p < 0.0001) and for longer lumen segments to be displayed on color mode (p < 0.0001). With the help of contrast medium, flow velocity in the middle cerebral artery could be measured through 65 windows as compared to only 26 windows before contrast was applied (p < 0.0001). CONCLUSIONS: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful.

Adult↗
PubMed2005

Increased prevalence of sleep apnea in patients with recurring ischemic stroke compared with first stroke victims.

Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio-respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty-four women and 68 men with a mean age of 64.5 +/- 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea-hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI >or=10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI >or=10/h", and "diabetes" identified diabetes (Odd's ratio [OR]=4.5) and AHI >or=10/h (OR=3.5) as independent risk-factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep-apnea screening in all patients having suffered an ischemic stroke.

Female↗
PubMed2005

Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial.

BACKGROUND: Evidence for efficacy of dual antiplatelet therapy in stroke is limited. Symptomatic carotid stenosis patients are at high risk of early recurrent stroke. In this group, asymptomatic microembolic signals (MES), detected by transcranial Doppler ultrasound (TCD), are markers of future stroke and transient ischemic attack (TIA) risk. They offer a surrogate marker to evaluate antiplatelet therapy, but no multicenter study has evaluated the feasibility of this approach. METHODS AND RESULTS: Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) is a randomized, double-blind study in subjects with recently symptomatic > or =50% carotid stenosis. Patients were screened with TCD, and if MES were detected, they were randomized to clopidogrel and aspirin or aspirin monotherapy. Repeated TCD recordings were made on days 2 and 7. MES were detected in 110 of 230 patients by online analysis at baseline, of whom 107 were randomized. Intention-to-treat analysis revealed a significant reduction in the primary end point: 43.8% of dual-therapy patients were MES positive on day 7, as compared with 72.7% of monotherapy patients (relative risk reduction 39.8%; 95% CI, 13.8 to 58.0; P=0.0046). The secondary end point of MES frequency per hour was reduced (compared with baseline) by 61.4% (95% CI, 31.6 to 78.2; P=0.0013) in the dual-therapy group at day 7 and by 61.6% (95% CI, 34.9 to 77.4; P=0.0005) on day 2. There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis; 2 additional ipsilateral TIAs occurred before treatment started. MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without (mean+/-SD: 24.4+/-27.7 versus 8.9+/-11.5 per hour; P=0.0003). CONCLUSIONS: In patients with recently symptomatic carotid stenosis, combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization. Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies.

Aged↗
PubMed2005

Cortical processing of esophageal sensation is related to the representation of swallowing.

The esophagus plays a major role in the act of swallowing. The aim of the present investigation was to apply whole-head magnetoencephalography in order to study the cortical processing of esophageal sensation in healthy humans in whom the cortical representation of swallowing had been established previously. The proximal esophagus was stimulated in nine participants by intermittent 5 ml water infusion. Submental EMG recording was used to identify trials, which were contaminated by subsequent swallowing. Esophageal stimulation led to changes in rhythmic activity of the brain that were localized in the left lateral primary sensorimotor cortex. The pattern of cortical activation showed the same hemispheric lateralization as that of volitional swallowing, however, being localized more lateral. The close anatomical vicinity of these two functions points to an important physiological link between the cortical processing of esophageal sensation and the cortical control of swallowing.

Adult↗
PubMed2005

Measuring carotid artery stenosis--comparison of postmortem arteriograms with the planimetric gold standard.

OBJECTIVE: Five different calliper methods for assessing the degree of carotid artery stenosis and visual estimation ("eyeballing") of postmortem carotid arteriograms were compared with the planimetric gold standard of the area reduction at the site of the stenosis. METHODS: During autopsy 53 carotid specimens were removed in toto from 31 neurological patients. Carotid arteries were ligated and redistended to a physiological degree for standardised three-plane arteriography. Afterwards, the entire specimen was filled with an embedding medium under the same conditions and sectioned. Slices at the site of stenoses were histologically processed. Computerised planimetric analysis of the lumen area reduction was performed and compared with the arteriographic findings. Arteriograms were evaluated by two independent observers by means of linear Common Carotid Artery (CC), the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and squared measurements (NASCET2, ECST2) after applying the pi r2 function. Further, three independent observers performed eyeballing of the degree of stenosis from the postmortem arteriographies. RESULTS: Planimetry was carried out in 29 internal carotid artery (ICA) and 17 common carotid artery (CCA) stenoses ranging from 8.5 to 100%. The smallest mean differences of the degree of stenosis in % between planimetry and arteriography were -0.5 and 0.6%. The narrowest 95 %-limits of agreement covered a range of +/-24.1 and 26.3% of stenoses, and the highest correlation coefficients were both 0.9 for the CC and ECST2 techniques, respectively. By eyeballing, the degree of stenosis was underestimated by 13.5 to 15.8% on average. The narrowest limits of agreement between two observers for eyeballing covered a range of 35%. CONCLUSION: Three-plane arteriography has only a moderate accuracy and reproducibility in detecting and measuring carotid artery stenosis independent of the technique of measurement used.

Aged↗
PubMed2005

High level of cerebral microembolization in patients supported with the DeBakey left ventricular assist device.

OBJECTIVE: Microembolic signals detected by transcranial Doppler ultrasonography have been demonstrated to be clinically relevant in patients supported with pulsatile left ventricular assist devices. We prospectively investigated the quantity of microembolic signals in patients supported with the continuous-flow DeBakey left ventricular assist device (MicroMed DeBakey VAD; MicroMed Technology, Inc, Houston, Tex) including the refined Carmeda BioActive Surface system (Carmeda AB, Stockholm, Sweden). METHODS: Twenty-three patients (20 male) aged 14 to 62 years supported with DeBakey left ventricular assist devices (n = 6 with Carmeda) were enrolled in this study. Microembolic signal monitorings were performed twice weekly by insonating the middle cerebral artery for 20 minutes without and 20 minutes with oronasal application of oxygen (6 L/min). Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: Despite a low incidence of thromboembolic complications (0.24 per 100 left ventricular assist device days), 20 patients (87%) showed circulating microemboli. Overall, microembolic signals were found in 175 of 499 transcranial Doppler ultrasonographic examinations (35.1%), with mean counts of 81.2 +/- 443 (range 0-5042 signals/h). Both microembolic signal prevalence (25% vs 34%, P = .01) and absolute signal counts (46.5 vs 104, P < .01) significantly declined with oxygen delivery. There was no significant correlation between the individual microembolic signal activity and the incidence of clinical thromboembolism or the intensity of antihemostatic treatment. Patients supported with the Carmeda device did not show reduced rates of clinical thromboembolization or cerebral microemboli. CONCLUSION: In patients with DeBakey left ventricular assist devices, a high load of clinically silent microemboli can be detected within the cerebral arteries despite a low incidence of embolic complications. It needs to be investigated whether such continuous, presumably gaseous microembolization causes cognitive or neuropsychologic deficits.

Adolescent↗