The mutation C677-->T in the methylene tetrahydrofolate reductase gene and stroke.
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Biomedical subjects
Publications and source records attributed to M Kaps.
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Two patients with acute occlusion of the middle cerebral artery (MCA) were treated with intravenous alteplase. Neurovascular monitoring, which was performed simultaneously via transcranial sonography, enabled precise documentation of MCA recanalization. This information was used to tailor the dosage and duration of alteplase treatment. Sonographic information concerning the arterial segments involved in the occlusive process, the actual hemodynamic status, and the collateral blood supply may help to identify those patients most likely to benefit from thrombolysis.
BACKGROUND: The pulmonary autograft procedure (Ross) is now considered the gold standard for aortic valve replacement. One of its advantages is the freedom from macroemboli without anticoagulation. Whether this holds true for circulating microemboli, detectable as high-intensity transient Doppler signals (HITS), has not yet been verified. METHODS AND RESULTS: We investigated 8 patients (2 women, 6 men; mean age, 50.6+/-17.9 years) after the Ross procedure, 9 patients (3 women, 6 men; mean age, 67.2+/-9.46 years) after aortic valve replacement with a mechanical valve prosthesis, and 12 young healthy volunteers by unilateral 1-hour recording of the middle cerebral artery on digital audio tape. Patients with extracranial carotid artery disease were excluded by color duplex sonography. During the off-line evaluation, the investigator was not aware of any patient details. No HITS were detected in healthy volunteers (95% confidence interval [CI], 0% to 26.46%). After the Ross procedure, 1 patient had 11 and 1 patient had 1 HITS (95% CI, 3.19% to 65.09%). All recipients of mechanical valves had HITS, ranging from 2 to 84 per hour (95% CI, 66.7% to 100%). Significantly more recipients of mechanical valves exhibited HITS than recipients of pulmonary autografts (P<.05) or control subjects (P<.05). CONCLUSIONS: In contrast to mechanical valves, pulmonary autografts are seldom the source of microemboli, confirming the pulmonary autograft as the superior substitute for aortic valve replacement.
OBJECTIVE: By means of transcranial Doppler sonography (TCD), microembolic signals (MES) representing embolic events can be registered during cardiac surgery and extracorporeal circulation in a considerable number of patients. We conducted the present study to determine the neuro-psychiatric consequences of MES. METHODS: 25 patients scheduled for elective aorto-coronary bypass grafting (ACBG; n = 10) or aortic valve replacement (AVR; n = 15) were studied pre- and postoperatively with neuropsychiatric testing. Results were related to the number of MES noted intraoperatively. In addition, we registered the intraoperative changes of middle cerebral artery blood flow velocity, mean arterial pressure, arterial blood gases, haemoglobin and haematocrit. Statistics included t-test, two-way analysis of variance, Mann-Whitney-U-test and Spearman correlation with p < 0.05 considered significant. RESULTS: Regarding demographic data and intraoperative parameters, both study groups (ACBG vs. AVR) were comparable except for age. AVR patients showed significantly more MES than those undergoing ACBG (p < 0.012) which was most pronounced in the late state of surgery (aortic clamp off; p < 0.0003). However, MES counts did not correlate with neuropsychiatric test results. CONCLUSIONS: In contrast to recent reports, we were unable to show a deterioration of postoperative neuropsychiatric state related to high intraoperative MES count in our patients. Future TCD studies should focus on the differentiation between gaseous emboli and particles even in the clinical setting, as the latter may well play a major role for the development of cerebral dysfunction following cardiac surgery and extracorporeal circulation.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary stroke disease linked to chromosome 19 q 12. We report on two families affected by this disease, which is characterised by recurrent subcortical ischaemic strokes, progressive pseudobulbar palsy, and presenile dementia. Neuroimaging revealed multiple deep infarcts and diffuse leukoencephalopathy. Diagnosis of CADASIL based on the typical clinical feature without vascular risk factors, the neuroradiological signs of extensive leukoencephalopathy, and the autosomal dominant pattern of inheritance. CADASIL might be an underestimated cause of familial stroke and should be considered in the differential diagnosis of hereditary stroke.
Besides the degree of carotid artery stenosis, the composition of the plaque may help to predict the thromboembolic risk. Low echogenicity on ultrasound and hemorrhage into the atheroma demonstrated histopathologically have been shown to be associated with a higher risk of embolism. Twenty-nine consecutive patients with carotid artery stenosis and scheduled for carotid endarterectomy were investigated preoperatively by B-mode ultrasound. Post-operatively the endarterectomy specimens were examined histopathologically. Neither atheroma with hemorrhage nor atheroma without hemorrhage were significantly associated with echolucent ultrasound presentation. Out of the 10 lesions echolucent and homogeneous on ultrasound, six corresponded to atheroma with hemorrhage, two corresponded to atheroma with hemorrhage plus thrombus, two corresponded to fibrous plaque plus thrombus, and one corresponded to pure thrombus. Out of the 4 lesions heterogeneous and predominantly echolucent, one corresponded to atheroma without hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage, one corresponded to atheroma with hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage plus fibrous plaque. Seven out of the 18 atheromas with hemorrhage did not present as purely or predominantly echolucent lesions, six of them were even homogeneously echogenic. Plaque surface could not reliably be predicted by ultrasound. In our study, there was no significant correlation between ultrasound and histology of the lesion.
OBJECTIVES: To study the effects of different colour imaging modes on the contrast-medium-enhanced image of the intracranial cerebral arteries. METHODS: Twelve healthy volunteers were studied transcranially after administration of 10 ml BY963 successively with Power Doppler (p-TCCS) and with colour Doppler frequency imaging mode (f-TCCS) in a randomized order. RESULTS: The latency time (mean+/-SD) from the injection until the signal enhancement in the middle cerebral artery was 17.1+/-5.8 s for p-TCCS and 17.8+/-4 s for f-TCCS, and the duration of the optimal diagnostically useful signal enhancement was 44.2+/-8.2 s and 40.2+/-12.6 s respectively. CONCLUSIONS: Based on the measured parameters, both imaging modes were of equal value. Theoretical differences in sensitivity of the two methods play no particular role facing the immense signal enhancement after echo contrast application.
OBJECTIVES: To determine whether an increase in plasma concentration of S-100 protein can serve as a marker for acute exacerbation of multiple sclerosis. MATERIAL AND METHODS: The plasma level of S-100 protein was investigated in 28 patients suffering from multiple sclerosis. Of these, 17 patients were admitted for acute exacerbation and 11 patients had a stable disease with no clinical signs for acute exacerbation. S-100 protein concentrations in plasma were determined with an immunofluorometric sandwich assay. RESULTS: Plasma concentrations were significantly elevated in patients who were examined within 7 days after the onset of acute exacerbation (n = 6). S-100 levels of patients 8 to 28 days after the onset of acute exacerbation (n = 11) did not differ from healthy controls (n = 120). Eleven patients with multiple sclerosis without acute exacerbation had moderately elevated plasma levels. CONCLUSION: The plasma concentration of S-100 protein is a sensitive although unspecific indicator of neuronal damage and may be of use as a marker of disease activity in multiple sclerosis.
OBJECTIVES: Isolated infarcts of the pons cause well definable neurological syndromes with distinct pathomechanism, clinical course and prognosis. PATIENTS AND RESULTS: We report 8 cases suffering from a pure motor hemiparesis that was severely progressive within the 1st 3 days and unresponsive to aspirin. A relatively good recovery was observed in all patients, however, stroke recurrence occurred in 2 cases within 3 months and resulted in pseudobulbar paralysis and tetraparesis. MRI displayed unilateral (n=6) and bilateral (n=2) ventromedial pontine infarctions (VPI). Angiographic evaluation (n=4) or color Duplex examination (n=4) revealed atherosclerotic lesions but no basilar artery occlusion. CONCLUSION: Although VPI due to basilar branch disease may clinically mimic a classical lacunar syndrome, it is related to a particular pathogenetic mechanism different from microangiopathy or embolism. In contrast to the MRI feature of lacunes, VPI typically extend to the basal surface of the pons. The progressive pattern, ending up in a relative uniform clinical picture, is probably caused by propagating thrombosis.
BACKGROUND AND PURPOSE: In the carotid bifurcation, atherosclerotic plaques usually develop in the outer wall of the internal carotid artery. The aim of this study was to analyze the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the carotid bifurcation. These molecules play a role in inflammatory cell recruitment and atherosclerosis. METHODS: We examined the expression of ICAM-1, VCAM-1, and E-selectin in 22 human carotid bifurcation specimens by means of immunohistochemistry. Double immunostaining was performed with antibodies against CD-3, CD-31, CD-68, and alpha-smooth muscle actin combined with each of the cell adhesion molecule antibodies. In situ hybridization for ICAM-1 was performed in selected specimens. RESULTS: A profound focal expression of ICAM-1 in the outer wall of the internal carotid artery could be demonstrated (86% of all specimens). This focal expression could be shown in histologically normal appearing bifurcations of young adults. ICAM-1 was expressed by subsets of macrophages and smooth muscle cells and by endothelial cells. VCAM-1 and E-selectin showed no focal expression and were not found in normal carotids. In advanced plaques all three adhesion molecules-ICAM-1, VCAM-1, and E-selectin-were expressed. CONCLUSIONS: We were able to demonstrate a focal expression of ICAM-1 in the outer lateral wall of the internal carotid artery, which is a high-risk region for the development of atherosclerotic lesions.
BACKGROUND AND PURPOSE: Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke. METHODS: Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale. RESULTS: Peak blood levels of S-100 protein were found on day 2.5 +/- 1.3, and peak levels of NSE were found on day 1.9 +/- 0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (r = .75, P < .001) and with clinical outcome assessed with the Glasgow Outcome Scale (r = .51, P < .001). Serum levels of NSE correlated with infarct volume (r = .37, P < .05) but not with clinical outcome (r = .18, P > .05). CONCLUSIONS: The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.
BACKGROUND AND PURPOSE: Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. The composition of these emboli in different clinical conditions is unclear. METHODS: We performed 1-hour transcranial Doppler sonographic recordings from the middle cerebral or posterior cerebral artery in 20 patients with mechanical prosthetic heart valves, in 78 patients with an arterial embolic source, and in 20 control subjects. During 30 minutes of this recording, the patients inspired room air and 6 L of oxygen per minute via a loosely fitting facial mask; during the remaining 30 minutes, they breathed room air only. RESULTS: There was a significant decline of embolic signals (ES) under oxygen in the patients with mechanical prosthetic cardiac valves (144 ES without oxygen versus 63 ES with oxygen; P = .002) but not in the patients with arterial embolic sources (145 ES without oxygen versus 135 ES with oxygen; P = NS). In the control subjects, no ES were found. CONCLUSIONS: ES in patients with mechanical prosthetic cardiac valves correspond mainly to gas bubbles. Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. In contrast, solid microemboli originating from thrombus or atheroma cannot be suppressed by oxygen inhalation. This simple method of oxygen inhalation should help to clarify the composition of microemboli in various clinical and experimental settings.
BACKGROUND AND PURPOSE: Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood. METHODS: Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber. RESULTS: Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa). CONCLUSIONS: The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.
BACKGROUND AND PURPOSE: Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now being widely investigated in the hope of identifying patients at increased risk for stroke. Automatic detection by bigated Doppler, which uses sampling from two different depths in the artery under study and considers the motion of the embolus, may help to define "periods of interest" that can be evaluated off-line. METHODS: In 12 normal volunteers and 10 patients with prosthetic aortic valves, we performed 1-hour recordings from one middle cerebral artery. In the normal subjects, we produced additional artifacts to use them as false-positives. Detection of microemboli was done off-line from digital audiotapes by an experienced blinded investigator (used as the gold standard) and was compared with on-line detection using specially designed software. RESULTS: With the setting used, 91.5% of all recorded artifacts could correctly be identified as such with the software. Embolic signals were detected by the software with a specificity of 59.9% and a sensitivity of 74.3%. CONCLUSIONS: Bigated Doppler adds a new dimension to the definition and detection of microembolic signals. It constitutes an important step forward toward automatic screening of stroke-prone patients. Assessing on-line periods of interest during the recording and going over the recorded data again off-line helps to save time for the discrimination of embolic signals from both the normal Doppler spectrum background and artifacts.
BACKGROUND AND PURPOSE: Ultrasound attenuation caused by the skull is a major limitation of transcranial Doppler. Echocontrast agents (EAs) may solve this problem. The aim of the present study was to investigate the characteristics of a new echocontrast agent (BY963) containing air bubbles stabilized by phospholipids. METHODS: Nine healthy volunteers received three different doses (2.5, 5.0, and 10 mL) of BY963 at an injection rate of 0.25 mL/s. The Doppler signal amplitude obtained from the middle cerebral artery was recorded with a 2-MHz pulsed-wave Doppler system. After complete decay of the signal enhancement, upward stroking of the veins of the upper arm was performed to evaluate the stability of the EA in the venous system. RESULTS: A dose-dependent increase of at least 30 dB in the Doppler signal amplitude lasted 19 to 47, 35 to 64, and 48 to 126 heart cycles (68% range) after 2.5, 5.0, and 10 mL EA, respectively. In 6 cases, there was a biphasic increase in EA enhancement. Upward stroking of the forearm, in general 12 to 18 minutes after administration, caused a Doppler signal enhancement of at least 30 dB in 6 cases. CONCLUSIONS: Each injection of BY963 caused a diagnostically relevant Doppler signal enhancement. A considerable amount of EA remained stable in the venous system for at least 12 minutes. The biphasic dose-response fits to models of dilution-indicator theory and indicates free recirculation, as well as a nonlinear washout curve.
BACKGROUND AND PURPOSE: Gas bubbles of ultrasound contrast agents resonate at frequencies used for diagnostic ultrasound and produce harmonics or multiples of the transmitted frequency. Processing of the second harmonic frequency results in a reduction of the signal-to-noise ratio and the signal-to-tissue artifacts. This study is the first to evaluate second harmonic imaging in the cerebral circulation. METHODS: We used a duplex system (HP SONOS 2500) in connection with a 1.8/3.6-MHz (second harmonic) and a 2.5-MHz (conventional) sector transducer. Levovist (6.5 mL; 400 mg/mL) was injected intravenously for second harmonic and conventional color duplex imaging in 13 healthy volunteers (age range, 23 to 34 [median, 29] years). RESULTS: When second harmonic imaging was compared with conventional color duplex imaging, more cerebellar arteries were detected (35 versus 31), the duration of blooming artifact was significantly reduced (7.9 versus 29.9 seconds; P = .03), and the duration of diagnostically useful signal enhancement was increased (248.5 versus 117.4 seconds; P = .0003), but the maximal investigation depth was reduced (8.4 versus 9.3 cm; P = .001). When conventional and second harmonic duplex were compared, there was a significant (P < .04) difference in the systolic blood flow velocity in the vertebral and basilar arteries. CONCLUSIONS: Second harmonic color duplex imaging in the vertebrobasilar system increases the time of diagnostic useful signal enhancement and produces a better spatial resolution compared with conventional color duplex imaging.
We conducted a two-way selection experiment in a composite rabbit population to investigate the responses to selection for postweaning ADG and feed conversion (FC). Two generations of crossing, followed by four generations of random pair matings, preceded three generations of selection. Selection was practiced within four lines: high-feed conversion (HFC), low-feed conversion (LFC), high gain (HG), and low gain (LG). Data on 1,446 rabbits from the random mating and selection generations were fitted to an animal model to estimate heritabilities of and the genetic correlation between ADG and FC. The two-trait model included rabbit and common litter random effects and line, generation, and sex fixed effects. Estimates of heritability of ADG and FC were .48 and .29, respectively, and the genetic correlation between them was -.82. Common litter environmental effects accounted for a proportion of .11 and .13 of the phenotypic variation of the two traits, respectively. For ADG (in g/d) the regressions of mean breeding values on generation number during the selection period were 1.23 +/- .12 (P < .01) in the HG line and -.86 +/- .12 (P < .01) in the LG line; the regressions for FC (in g feed/g gain) were -.07 +/- .01 (P < .01) in the HFC line and .03 +/- .01 (P < .05) in the LFC line. Selection for ADG was effective in improving ADG and FC.
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