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Biomedical subjects

E B Ringelstein

Publications and source records attributed to E B Ringelstein.

At least 73 records · Page 4Linked to original sources

Long-term prevention of ischaemic stroke and stroke recurrence.

Stroke is the third most important cause of mortality, but the leading cause of severe handicap, dependency, and loss of social competence. Because of the high recurrence rate, active secondary prevention is mandatory once a stroke has occurred. Secondary prevention of stroke implies the primary prevention of cardiovascular disorders as well. Among the modifiable risk factors hypertension is worst and should be normalized according to recent WHO criteria, also in the elderly. Smoking is another major risk factor and hard to delete. Diabetes mellitus and hyperlipidaemia are also important risk factors and should be treated consequently by diet and medication. Moderate alcohol intake, normalization of body weight and regular physical activity also contribute considerably to prevention of stroke. Whether hyperhomocysteinaemia should be normalized has not yet been clarified. Cardiovascular disorders are an important source of ischemic strokes, particularly atrial fibrillation. Low dose anticoagulation can dramatically reduce stroke risk. Carotid endarterectomy in symptomatic stenoses is the most expensive means of stroke prevention. In less severe stenoses, or ICA occlusions, antiplatelet agents are the treatment of choice. Composite drugs with ASS and other antiplatelet agents seem to be superior to either compound alone. Dissections of the cervical arteries should not be operated on but may be treated by anticoagulation or antiplatelet agents in the acute and subacute phase. The potency of a consequent and comprehensive stroke prevention in preventing disability and death is much greater than any sophisticated acute stroke treatment.

Arteriosclerosis↗

[Knowledge about stroke among the German population].

BACKGROUND AND OBJECTIVE: Modern stroke therapy requires patients to correctly identify stroke symptoms and seek immediate hospital admission. US studies showed that only 57% of the population knew at least one stroke symptom. This is the first study about stroke knowledge among German populations. METHODS: Using a cross-sectional questionnaire survey, 300 working-age participants of the PROCAM study, the Prospective Cardiovascular Münster Study, and 95 senior citizens of the Augsburg Study, a follow-up project of the MONICA survey 1989/90, were asked about stroke symptoms and what to do if they occur. Good knowledge about stroke was defined as knowing at least two stroke symptoms and calling the emergency medical system or seeking immediate hospital admission in case of symptoms. RESULTS: Participation rate in the PROCAM study was 90%, while all senior citizens took part. The mean age of the working population was 41.2 years, the mean age of the retired population was 72.8 years. 35% of the working and 24.5% of the retired participants knew at least two stroke symptoms. Urgent hospital admission was selected by 78.2% of the occupational but only 41.5% of the retired participants. Good stroke knowledge was demonstrated by nearly a third of the workers but less than 10% of the elderly. Among the occupational population, being a white-collar worker or knowing someone with a stroke was a significant predictor of good stroke knowledge. Among senior citizens higher age and current smoking status were significant predictors. CONCLUSION: Our study shows significant information deficits about stroke in our population: education needs to be geared especially towards the elderly.

Adult↗

PMP22 Thr118Met is not a clinically relevant CMT1 marker.

It is controversial if peripheral myelin protein 22 gene (PMP22) Thr118Met represents a functionally irrelevant polymorphism or, since hemizygosity for this variant has been found in two patients with Charcot-Marie-Tooth disease type 1 (CMT1 patients), it can act as a recessive CMT1 mutation. To shed further light on this variant and its diagnostic value we searched for carriers in 1018 individuals from the German general population, in 104 probands with hereditary neuropathy with liability to pressure palsies (HNPP) who were carriers of the 1.5-Mb deletion frequently associated with this disorder, in 187 patients with the 1.5-Mb duplication, and in 22 patients with a CMT1 phenotype who did not have any detectable anomaly in the PMP22 gene. Using allele-specific PCR we identified 14 [allele frequency (AF)=0.007] in the German general population, one (AF=0.01) in the HNPP group and six (AF=0.016) and two (AF=0.05) carriers of the PMP22 Thr118Met mutation in the CMT1 groups with and without gene defect. Carriers from all groups showed nerve conduction velocities which did not differ from typical values for these groups. We conclude that the hemizygous occurrence of the 118Met allele does not usually cause CMT1. Because of previous reports on its association with disease, and because its allele product shows abnormalities in in vitro expression systems, it seems possible that this mutation, together with yet unidentified factors, predisposes to CMT1. Alternatively, previously reported disease associations occurred by chance, and the 118Met allele causes biochemical abnormalities irrelevant for CMT1 formation. In either case this mutation is not a clinically relevant disease marker.

Biomarkers↗

Co-localization of multiple antigens and specific DNA. A novel method using methyl methacrylate-embedded semithin serial sections and catalyzed reporter deposition.

Co-localization of proteins and nucleic acid sequences by in situ hybridization and immunohistochemistry is frequently difficult as the process necessary to detect the target structure of one technique may negatively affect the target of the other. Morphological impairment may also limit the application of the two techniques on sensitive tissue. To overcome these problems we developed a method to perform in situ hybridization and immunohistochemistry on semithin sections of methyl methacrylate-embedded tissue. Microwave-stimulated antigen retrieval, signal amplification by catalyzed reporter deposition, and fluorescent dyes were used for both techniques, yielding high sensitivity and excellent morphological preservation compared to conventional paraffin sections. Co-localization of in situ hybridization and immunohistochemistry signals with high morphological resolution was achieved on single sections as well as on adjacent multiple serial sections, using computerized image processing. The latter allowed for the co-localization of multiple antigens and a specific DNA sequence at the same tissue level. The method was successfully applied to radiation bone marrow chimeric rats created by transplanting wild-type Lewis rat bone marrow into TK-tsa transgenic Lewis rats, in an attempt to trace and characterize TK-tsa transgenic cells. It also proved useful in the co-localization of multiple antigens in peripheral nerve biopsies.

Animals↗

Preoperative B-mode ultrasound plaque appearance compared with carotid endarterectomy specimen histology.

In carotid artery stenosis both the degree of the lesion and its plaque morphology are thought to be associated with the carrier's thromboembolic risk. In this study we evaluated the diagnostic preciseness of non-invasively B-mode ultrasound in predicting the histopathological plaque structure. We examined 44 patients with > 50% ICA stenosis by B-mode within 6 weeks prior to carotid endarterectomy. At the affected bifurcations, up to 10 different regions of interest (ROI) per artery were investigated. Plaque appearance was classified according to 6 subtypes considering different ultrasonic plaque features. Postoperatively, plaque specimens were examined histopathologically for their relative content of calcification, fibrous tissue and different soft tissue. B-mode ultrasound was compared with histopathological features in ROI. A total of 265 regions of interest were evaluated. In mainly echolucent types of plaques, atheromatous debris was most frequently seen, whereas fibrosis was rare. Homogeneous echolucent plaques showed a high proportion of cholesterol and/or recent haemorrhage. Thrombosis at the plaque surface was often seen in "completely echolucent" plaque type (each P<0.001). Carotid B-mode ultrasonography is able to predict the histopathological components and the texture of carotid plaques.

Adipose Tissue↗

Ultrasound contrast enhancing agents in neurosonology: principles, methods, future possibilities.

OBJECTIVES: Ultrasound of the brain supplying arteries is a standard diagnostic procedure in patients with suspected and definite acute and chronic cerebrovascular occlusive disease. Anatomical and pathological limitations led to the development of echocontrast agents which are able to survive pulmonary and capillary transit and improve the echogenicity of the flowing blood. MATERIAL AND METHODS: This article reviews present and future applications of echocontrast agents in conjunction with personal experiences. RESULTS: Currently, echocontrast is used for the differentiation of internal carotid artery occlusion and pseudoocclusion, better delineation of the maximal narrowing in high-grade stenoses, and better visualization of the extracranial vertebral artery and its collaterals. Transcranial applications include the insufficient foraminal or temporal window, assessment of arteriovenous malformations, thrombosis of cerebral veins and sinuses, and intracranial aneurysms. The use of echocontrast can have direct diagnostic and therapeutic consequences. Harmonic imaging, perfusion imaging, stimulated acoustic emission, and drug delivery are possible future domains of the technique. DISCUSSION: Besides the support of conventional neurovascular ultrasound in poor examination conditions due to the patients' anatomy or pathology, echocontrast agents may allow for novel applications in the diagnosis and treatment of cerebrovascular patients.

Carotid Artery Diseases↗

Maternal cerebral hemodynamics in pregnancy-related hypertension. A prospective transcranial Doppler study.

AIM: To compare maternal cerebral hemodynamics, as assessed by transcranial Doppler studies, with the clinical and radiological findings in different types of pregnancy-related hypertension and to determine their pathophysiology. METHODS: A prospective study of 66 consecutive pregnant women with hypertensive disorders (eclampsia, n = 3; pre-eclampsia, n = 41; isolated hemolysis, elevated liver enzymes, and low platelet count (HELLP)-syndrome, n = 12; pre-eclampsia superimposed on chronic hypertension, n = 5; chronic hypertension, n = 5) and 21 women with uncomplicated pregnancies. Mean blood flow velocities (Vmean) were assessed serially by means of transcranial Doppler in all basal arteries and correlated with changes in mean arterial blood pressure (MABP) and the clinical course. RESULTS: Patients with the pre-eclampsia/eclampsia syndrome showed significantly elevated Vmean values as compared to controls. In the course of the illness Vmean over the whole length of all insonated basal arteries rose simultaneously. The three eclamptic patients showed the highest Vmean values (156, 182, 192 cm/s, respectively), of the middle cerebral artery (MCA) while MABP was 135, 135, and 150 mmHg, respectively. In pre-eclamptic patients the maximal Vmean MCA ranged from 80 (67, 93) to 145 (114, 151) cm/s [median (25th, 75th percentile)] depending on the severity of clinical presentation. In patients with isolated HELLP-syndrome changes in Vmean were either mild (5/12 cases) or absent (7/12 cases). CONCLUSIONS: Considerable differences in cerebral hemodynamics were observed in the various types of pregnancy-related hypertensive disorders examined in this study. Our findings in patients with pre-eclampsia/eclampsia syndrome suggest a breakdown of autoregulation with hyperperfusion and vasogenic edema being the most probable pathophysiological mechanism.

Cerebrovascular Circulation↗

Oncostatin M-mediated growth inhibition of human glioblastoma cells does not depend on stat3 or on mitogen-activated protein kinase activation.

Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary neurotrophic factor and leukemia inhibitory factor, can induce differentiation of glial cells. We have recently described that OSM inhibited the growth of human glioma cells in vitro and induced a cell morphology resembling that of mature astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increase in glial fibrillary acidic protein expression. The differentiation and the growth inhibition were not significantly blocked by expression of a dominant-negative (dn) signal transducer and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA synthesis even in the presence of a high expression level of dnStat3. Moreover, inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM effect, indicating that the activation of this pathway counteracts the activity of the cytokine.

Antineoplastic Agents↗

Handedness and hemispheric language dominance in healthy humans.

In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between handedness and dominance has long been suspected. To clarify the relationship between handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-handedness, from 4% in strong right-handers (handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (handedness = -100). The relationship could be approximated by the formula: f1.gif" BORDER="0">. These results clearly demonstrate that the relationship between handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.

Adolescent↗

Assessment of hemispheric language lateralization: a comparison between fMRI and fTCD.

The cerebral blood flow velocity (CBFV) in the basal arteries during a word-generation task was assessed by functional transcranial Doppler ultrasonography (fTCD) and by functional magnetic resonance imaging (fMRI). The study investigates how event-related CBFV modulations in the middle cerebral artery (MCA) relate to regional cerebral blood flow (rCBF) changes. Both fMRI and fTCD were used in 13 subjects (7 men, 6 women, aged 21 to 44 years). The maximum difference of relative CBFV changes between the left and right MCA during the word-generation task was used as the language laterality index (LIfTCD). For the fMRI examination during the nearly identical language task, the corresponding index was defined by LIfMRI = 100(N(L) - N(R))/(N(L) + N(R)), where N(L) and N(R) refer to the numbers of voxels activated in the left and right hemisphere, respectively. The evoked CBFV changes expressed by LIfTCD and the corresponding laterality index, LIfMRI, estimated by fMRI showed a close linear relation (regression analysis: r = 0.95, p < 0.0001). The results of this study demonstrate that language-related velocity changes in the MCAs relate to rCBF increases in a linear fashion. Since the laterality indices assessed by fMRI and fTCD are in such close agreement both techniques can therefore be used in a complementary way.

Adult↗

Transcranial Doppler ultrasonography: year 2000 update.

In this update, the main clinical applications of transcranial Doppler ultrasonography are reassessed. A specific format for technology assessment, personal experience, and an extensive review of the literature form the basis of the evaluation. The document is approved by the American Society of Neuroimaging and the Neurosonology Research Group of the World Federation of Neurology.

Brain Diseases↗

Benefit of echocontrast-enhanced transcranial color-coded duplex ultrasound in the assessment of intracranial collateral pathways.

BACKGROUND AND PURPOSE: Although clinically important, proper assessment of intracranial arterial collateral pathways by transcranial color-coded duplex sonography (TCCD) in patients with internal carotid artery (ICA) high-grade stenosis or occlusion 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. METHODS: We investigated 50 temporal windows of 44 patients with ipsilateral high-grade (>/=70%) ICA stenosis or occlusion and insufficient native transtemporal insonation conditions before and after the application of the echo enhancer Levovist with an infusion pump. RESULTS: Compared with 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). Also, collateral flow via the anterior and posterior communicating artery could be demonstrated in 25 and 32 scans, respectively, compared with only 1 demonstration of each collateral pathway before the application of contrast medium (both P<0.0001). Similarly, with the help of contrast medium, flow velocity in the middle cerebral artery could be measured in 45 cases compared with only 26 cases before contrast was applied (P<0.0001). CONCLUSIONS: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful in the assessment of intracranial collateral pathways recruited downstream to ICA stenoses and occlusions.

Adult↗

Visualization of the basilar artery by transcranial color-coded duplex sonography : comparison with postmortem results.

BACKGROUND AND PURPOSE: Transcranial color-coded sonography (TCCS) via the suboccipital approach allows direct and continuous visualization of the basilar artery (BA). In this study, we intended to evaluate the ability of native TCCS in visualizing the length of the BA by means of a comparison with postmortem measurements. METHODS: The BA was prospectively studied by TCCS shortly before death (median 3 days) in 46 moribund neurological patients (mean+/-SD age 71.1+/-13.1 years). The length of the BA was determined by measuring the distance between the vertebrobasilar junction and the deepest available flow signal in the top of the BA. During autopsy, photos of the vertebrobasilar system were taken to evaluate the true anatomic length and variations of the course of BA in situ, eg, straight, curved, or S-shaped. RESULTS: Comparison of the in vivo ultrasound measurements of BA length and postmortem data was possible in 44 of 46 cases. In the 2 remaining patients, the BA was occluded. The mean insonation depth of the vertebrobasilar junction was found at 66.9+/-7.1 mm. The mean BA length was 21.5+/-6. 8 mm by color-coded duplex and 32.9+/-6 mm anatomically (P<0.0001). The mean difference between color mode and anatomic findings was 11. 3+/-6.4 mm in the case of a straight BA (35 cases) and 16.3+/-4.8 mm in an anatomically tortuous course of the BA (9 cases). CONCLUSIONS: Color duplex imaging enables correct visualization of the proximal two thirds of the BA, but only exceptionally of its distal one third. A tortuous course of the BA leads to an underestimation of its anatomic length.

Basilar Artery↗

Stroke knowledge among stroke support group members.

BACKGROUND AND PURPOSE: Community stroke education is needed to improve early stroke recognition and reduce delays in the referral of stroke patients. In some regions, stroke support groups are important promoters of regional stroke education. However, there are no data about the level of stroke knowledge among support group members that support this promotional role. METHODS: We performed a cross-sectional questionnaire survey among 11 German stroke support groups. The questionnaire asked for stroke knowledge and sociodemographic and medical data. Stroke knowledge was excellent if a participant knew (1) at least 2 stroke symptoms (good symptom knowledge) and (2) at least 2 stroke risk factors (good risk factor knowledge), as well as knowing (3) that immediate hospital admission or an emergency call is necessary in case of stroke (good action knowledge). RESULTS: A total of 133 members (96.2%) of 11 stroke support groups took part in the study. Mean age was 65.3 years (SD 11.2 years). Fifty-four percent of subjects were female, 72.8% were retired, and 69.8% were stroke patients. Of the participants, 80.3% had good symptom knowledge, 64.7% had good risk factor knowledge, and 79.7% had good action knowledge. Stroke knowledge was excellent in 44.0% of subjects. Logistic regression analysis showed that age <70 years and not having had a stroke were significant predictors for excellent stroke knowledge. CONCLUSIONS: Overall, members of stroke support groups are well informed about all aspects of modern stroke care. Because of their knowledge and personal experience, support groups should be viewed as important partners in community stroke education.

Aged↗

Contrast transcranial doppler ultrasound in the detection of right-to-left shunts : time window and threshold in microbubble numbers.

BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation procedure. Currently, data on the appropriate timing of the VM, the use of a diagnostic time window, and a threshold in contrast agent microbubbles detected are insufficient. METHODS: Fifty-eight patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with injections of 10 mL of the commercial galactose-based contrast agent Echovist was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds after the beginning of contrast injection, (3) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, (4) VM for 5 seconds starting 8 seconds after the beginning of contrast injection, and (5) repetitive short VMs in between 2 and 13 seconds after the beginning of contrast injection. In addition to the single tests, we also tested the sensitivity and specificity of combined results of the tests with VM. RESULTS: In 21 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 16 patients were only positive on at least 1 TCD investigation but negative during TEE. Test 3 was the most appropriate test when combined with the results of 1 of the other tests with VM. The highest sensitivities were achieved with a diagnostic time window of 40 seconds and when the presence of a single microbubble was sufficient for the diagnosis of a shunt. CONCLUSIONS: TCD performed twice with 2 provocation maneuvers with Echovist is a sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM should be performed for 5 seconds starting at 5 seconds after the beginning of contrast injection.

Adolescent↗

One-year follow-up of neuropsychology, MRI, rCBF and glucose metabolism (rMRGlu) in cerebral microangiopathy.

BACKGROUND: MRI shows lacunar infarctions (LI), deep white matter lesions (DWML) and atrophy in cerebral microangiopathy, which is said to lead to vascular dementia. In a first trial series on 57 patients with confirmed pure cerebral microangiopathy (without concomitant macroangiopathy), neuropsychological impairment and (where present) brain atrophy correlated with decreased rCBF and rMRGlu. LI and DWML did not correlate with either neuropsychological impairment or decreased rCBF/rMRGlu. This study was done one year later to detect changes in any of the study parameters. METHODS: 26 patients were re-examined for rCBF, rMRGlu, LI, DWML, atrophy and neuropsychological performance (7 cognitive, 3 mnestic, 4 attentiveness tests). Using a special head holder for exact repositioning, rCBF (SPECT) and rMRGlu (PET) were measured and imaged slice by slice. White matter/cortex were quantified using MRI-defined ROIs. RESULTS: After one year the patients did not show significant decreases in rCBF or rMRGlu either in cortex or in white matter (p > 0.05), nor did any patient show LI, DWML or atrophy changes on MRI. There were no significant neuropsychological decreases (p > 0.05). CONCLUSIONS: Cerebral microangiopathy ought to show progressive neuropsychological, functional (rCBF, rMRGlu) and morphological deterioration over periods > 1 year. It is unlikely that direct cortical damage (e.g., incomplete infarction) is responsible for neuropsychological impairment since one-year follow-up of our patients revealed no progression of brain atrophy or any other cortical damage.

Adult↗