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H S Markus

Publications and source records attributed to H S Markus.

At least 55 records · Page 3Linked to original sources
PubMed1999

The use of the wavelet transform to describe embolic signals.

A number of methods to detect cerebral emboli and differentiate them from artefacts using Doppler ultrasound have been described in the literature. In most, Fourier transform-based (FT) spectral analysis has been used. The FT is not ideally suited to analysis of short-duration embolic signals due to an inherent trade-off between temporal and frequency resolution. An alternative approach that might be expected to describe embolic signals well is the wavelet transform. Wavelets are ideally suited for the analysis of sudden short-duration signal changes. Therefore, we have implemented a wavelet-based analysis and compared the results of this with a conventional FFT-based analysis. The temporal resolution, as measured by the half-width maximum, was significantly better for the continuous wavelet transform (CWT), mean (SD) 8.40 (8.82) ms, compared with the 128-point FFT, 12.92 (9.70) ms, and 64-point FFT, 10.80 (5.69) ms. Time localization of the CWT for the embolic signal was also significantly better than the FFT. The wavelet transform appears well suited to the analysis of embolic signals offering superior time resolution and time localization to the FFT.

Carotid Stenosis↗
PubMed1999

Mapping of cerebrovascular reactivity using BOLD magnetic resonance imaging.

Blood oxygen level-dependent (BOLD) contrast MRI is a simple non-invasive method of estimating "perfusion," and combined with a vasodilatory stimulus, may allow estimation of cerebral vascular reserve. We compared BOLD carbon dioxide (CO2) reactivity in the middle cerebral artery (MCA) perfusion territory to MCA flow velocity reactivity determined using transcranial Doppler ultrasound (TCD) in 16 patients with unilateral carotid artery stenosis or occlusion. Both BOLD and TCD reactivities were calculated from measurements acquired when the subjects were breathing air, and again when breathing a 6% CO2/air mixture, and were normalized by dividing by the difference in end tidal (ET) CO2. There was a significant correlation between interhemispheric MCA reactivity difference (contralateral-ipsilateral to the stenosis or occlusion) determined by BOLD MRI and TCD (r = 0.75, p < 0.001). In contrast, treating each hemisphere individually, there was no correlation between the absolute BOLD and TCD MCA CO2 reactivities (r = 0.08, p = 0.670). This appeared to be due to a variable BOLD signal change in the non-stenosed hemisphere between subjects, with little change in the normal hemisphere of a few subjects. In one patient, focal regions of reduced reactivity were seen in non-infarcted regions of the stenosed hemisphere, in the borderzones between arterial territories. BOLD reactivity maps provide information on the whole MCA territory reactivity, and may identify small regions of impaired reactivity which are not detected using TCD. However, BOLD reactivity maps only appear to provide semi-quantitative rather than quantitative data.

Adult↗
PubMed1999

Detection of distal emboli in patients with peripheral arterial stenosis before and after iliac angioplasty: a prospective study.

PURPOSE: Embolism is believed to be the major cause of end-organ damage after angioplasty and endoluminal procedures. Recently, Doppler ultrasound scanning has been used to detect asymptomatic cerebral emboli. We determined whether asymptomatic embolic signals (ES) could be detected distal to a significant iliac artery stenosis of >60% both before and soon after iliac percutaneous transluminal angioplasty (PTA). METHODS: A 2-MHz Doppler scan probe was used to monitor for ES in the common femoral artery before and after 10 successful iliac artery PTAs and at various standardized times in the following 24 hours. The same protocol was used to study 10 patients in the control group after renal PTA. In addition, a single recording was performed in a second nonoperative control group of 10 patients who had no evidence of peripheral vascular disease. The Doppler scan signals were recorded on tape for a later blinded analysis. RESULTS: In the 24 hours before iliac PTA, asymptomatic ES were detected in four of 10 patients during a 1-hour recording but in no controls (P =.025). After iliac PTA, ES were detected at 30 minutes in nine of 10 iliac subjects but in only one of 10 renal subjects (P =.0003) and at 2 hours in eight of 10 iliac subjects but in only one of 10 renal subjects (P =.001). The occurrence of ES became less frequent, and ES were present at a lower frequency in eight of 10 iliac PTA subjects at 4 hours and in five of 10 at 24 hours but in no renal PTA subjects at these time points. CONCLUSIONS: ES can be detected in the common femoral artery with Doppler ultrasound scanning in patients with iliac artery stenosis both before and soon after iliac PTA despite preangioplasty aspirin and intra-angioplasty heparin therapies. The occurrences of ES were particularly frequent in the 2 hours after PTA. This technique can be used further to study factors that control plaque stability and to evaluate the effect of therapeutic interventions.

Aged↗
PubMed1999

The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study.

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

Adult↗
PubMed1999

Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI.

BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

Adult↗
PubMed1999

Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group. METHODS: Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with >60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined. RESULTS: ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman's rho=-0.2558, P=0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4. 94 (95% CI, 1.23 to 19.84; P=0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (P=0.02) and asymptomatic patients (P=0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57; P=0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use. CONCLUSIONS: Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings.

Adult↗
PubMed1999

Clinical application of asymptomatic embolic signal detection in acute stroke: a prospective study.

BACKGROUND AND PURPOSE: The detection of asymptomatic embolization with the use of Doppler ultrasound has a number of potential applications in patients with acute stroke. It may provide information on the stroke pathogenesis in individual cases, identify patients with continued embolization, and allow localization of the active embolic source. METHODS: We recruited 119 patients with acute anterior circulation infarction within 72 hours of stroke onset. Transcranial Doppler recordings were possible in 100 (84.0%). Bilateral 1-hour middle cerebral artery (MCA) recordings were made and saved on digital audiotape for blinded offline analysis. When embolic signals were detected during screening of the first recording, simultaneous recording was performed from the ipsilateral MCA and common carotid artery for an additional 30 minutes. In all patients with embolic signals at screening and in matched negative controls, recordings were repeated on days 4, 7, and 14. RESULTS: Embolic signals were detected in the symptomatic MCA in 16 patients (16%). They were more common in patients with carotid stenosis (P<0.0001), occurring in 50% of this group. They were rare in patients with cardioembolic stroke (4.5%) and were not detected in patients with lacunar stroke. In the 16 patients with embolic signals, the proportion with embolic signals fell over time (P=0. 0025), but they were still present in a third at 2 weeks. In 10 patients, localization of the embolic source was possible by simultaneous recording from the MCA and the ipsilateral common carotid artery. CONCLUSIONS: Continued asymptomatic embolization is common after stroke in patients with carotid artery disease and is still present in a significant proportion at 2 weeks. The technique may identify patients at risk of further stroke for more aggressive antiplatelet therapy; this needs to be tested in large prospective studies. The technique may also allow localization of the active embolic source.

Acute Disease↗
PubMed1998

S-nitrosoglutathione reduces the rate of embolization in humans.

BACKGROUND: Antiplatelet agents presently used in the secondary prevention of cardiovascular disease fail to prevent the majority of cases of recurrent stroke and systemic embolization. An evaluation of the efficacy of new agents is hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic signals (ES) may be detected with the use of transcranial Doppler ultrasonography. These signals are particularly common after carotid endarterectomy, and this provides a situation in which new antiplatelet agents can be evaluated. With this model, we determined the effectiveness of S-nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet specificity, in reducing cerebral embolization. METHODS AND RESULTS: Transcranial Doppler ultrasound recordings from the ipsilateral middle cerebral artery were made after carotid endarterectomy in 12 control patients and 12 patients receiving intravenous GSNO from the induction of anesthesia until 2 hours after skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after skin closure. The Doppler signal was recorded onto tape, and analysis for ES was performed, with the investigators blinded to treatment group. All patients received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery. The median (range) number of ES detected during the initial 3-hour postoperative recording was markedly reduced in the GSNO group compared with the control group: 7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This difference persisted until 6 hours after surgery. CONCLUSIONS: Despite the administration of aspirin and heparin, frequent embolization occurred and was markedly reduced after the administration of GSNO. This demonstrates the potential use of platelet-specific nitric oxide donors in the treatment of thromboembolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.

Aged↗
PubMed1998

Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma.

OBJECTIVES: Chronic Helicobacter pylori infection has been associated with ischaemic heart disease although the mechanism by which it mediates this effect remains unclear. The objective was to determine whether it is also a risk factor for ischaemic cerebrovascular disease METHODS: A total of 238 patients and 119 controls were studied. Patients were characterised into stroke subtypes based on pathogenic mechanisms and carotid atheroma load was estimated using duplex ultrasound. H pylori seropositivity was determined on serum samples. RESULTS: H pylori seropositivity was more common in cases (58.8% v 44.5%, p=0.01). The odds ratio for cerebrovascular disease associated with seropositivity was 1.78 (95% confidence interval (95% CI) 1.14-2.77), and this remained significant after controlling for other risk factors including socioeconomic status (1.63 (95% CI 1.02-2.60). H pylori seropositivity was associated with large vessel disease (odds ratio 2.58 (95% CI 1.44-4.63), p=0.001) and lacunar stroke (odds ratio 2.21 (95% CI 1.12-4.38), p=0.02) but not stroke due to cardioembolism or unknown aetiology (odds ratio 1.16 (95% CI 0.66-2.02), p=0.5). Mean (SD) carotid stenosis was greater in patients seropositive for H pylori (37.3 (29.7) v 27.9 (26.2)%, p=0.01). There was no difference in the prevalence of seropositivity between patients with stroke and transient ischaemic attack (59.6% v 58.6%, p=0.9) CONCLUSION: Chronic H pylori infection is an independent risk factor for ischaemic cerebrovascular disease and may act, at least in part, by increasing atherosclerosis.

Aged↗
PubMed1998

Grading of cerebral dynamic autoregulation from spontaneous fluctuations in arterial blood pressure.

BACKGROUND AND PURPOSE: Assessment of cerebral autoregulation has been traditionally performed with static changes in arterial blood pressure. Newer dynamic methods require the induction of sudden drops in arterial blood pressure with the sudden release of bilateral thigh cuffs. An alternative method is proposed, based on the spontaneous variability of arterial blood pressure that does not require its manipulation. We compared this method with the established thigh cuff method in patients with carotid artery stenosis. METHODS: Cerebral blood flow velocity (determined by transcranial Doppler) and arterial blood pressure (determined by noninvasive servo-controlled plethysmograph) were recorded in 20 patients with carotid artery stenosis and 18 age-matched controls. At rest, grading of dynamic autoregulation was estimated from the impulse response of the blood pressure-velocity dynamic relationship. This was compared with the autoregulatory index (ARI) provided by the thigh cuff method and with the degree of stenosis. The critical closing pressure was derived from the fitted models and was also correlated with degree of stenosis. RESULTS: The 2 ARIs were significantly correlated (r=0.76) and reduced in subjects with carotid stenosis (baseline ARI, 3.65+/-3.11 versus 6.68+/-1.88, P<0. 0001; thigh cuff ARI, 3.78+/-2.32 versus 6.35+/-1.06, P<10(-5)). The critical closing pressure (relative to mean arterial blood pressure) was also significantly reduced (-0.24+/-1.06 versus 0.50+/-0.31, P<0. 0001) and correlated with the thigh cuff ARI (r=0.68). Both the baseline ARI and critical closing pressure were correlated with degree of stenosis (P<10(-6)). CONCLUSIONS: Grading of dynamic autoregulation with the use of undisturbed recordings of arterial blood pressure and cerebral blood flow velocity might provide a safer technique for assessment of patients in whom a sudden drop of arterial blood pressure is not desirable, such as patients with heart or autonomic failure.

Analysis of Variance↗
PubMed1998

Nitric oxide synthase inhibition in humans reduces cerebral blood flow but not the hyperemic response to hypercapnia.

BACKGROUND AND PURPOSE: Animal studies suggest that nitric oxide (NO) is important in basal cerebral blood flow (CBF) regulation and that it may mediate the vasodilatory response to carbon dioxide. We investigated its role in the human circulation using the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). METHODS: L-NMMA was administered as an intravenous bolus at three doses (1, 3, and 10 mg/kg). CBF was assessed by color velocity ultrasonic imaging of internal and common carotid artery volume flow (ICA flow and CCA flow) and transcranial Doppler ultrasound measurement of middle cerebral artery flow velocity (MCAv). The pressor effect of L-NMMA was controlled for by comparison with noradrenaline titrated to effect an equivalent blood pressure elevation. RESULTS: L-NMMA produced a dose-dependent reduction in basal mean+/-SD CCA flow from 415.2+/-51.9 to 294+/-56.2 mL/min (at 10 mg/kg) and ICA flow from 268.8+/-59.4 to 226.2+/-72.6 mL/min (P<.005 and P<.05, respectively, comparing areas under the dose-response curve). This was reversed by L-arginine. Mean+/-SD systemic blood pressure rose from 85.2+/-6.4 to 100.8+/-9.6 mm Hg (P<.01). There was no significant reduction in MCAv. There was no significant change in the CBF response to either 6% or 8% carbon dioxide after L-NMMA. Noradrenaline produced a lesser fall in basal CCA flow (12.0%) but had a similar effect on the hypercapnic response. CONCLUSIONS: Basal NO release is important in controlling human CBF, but intravenously administered L-NMMA does not inhibit the hypercapnic hyperemic response in humans. The discrepancy between CBF and MCAv after L-NMMA administration is consistent with MCA vasoconstriction. Neuronal NO synthase inhibition may be protective in stroke. However, our results suggest that nonselective NO synthase inhibitors such as L-NMMA should be used with caution because they reduce CBF.

Adult↗
PubMed1998

Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection.

Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Humans↗
PubMed1998

Temporal variability of asymptomatic embolization in carotid artery stenosis and optimal recording protocols.

BACKGROUND AND PURPOSE: Although asymptomatic embolization can be detected in patients with carotid artery stenosis, its temporal variability is unclear. An understanding of this is important in designing optimal recording protocols for future prospective studies of the predictive value of embolic signals (ES). We determined the effect of repeating and extending recording times in patients with symptomatic and asymptomatic carotid stenosis. METHODS: In 20 asymptomatic and 20 symptomatic subjects with > 60% carotid stenosis, we used transcranial Doppler ultrasound to record for ES in the ipsilateral middle cerebral artery. Three 1-hour recordings were performed on three separate days, and on one occasion (not necessarily the first) the recording was extended to 2 hours. The recordings were saved onto digital tape for subsequent blinded analysis. RESULTS: Marked temporal variability was seen in symptomatic patients in whom the cumulative proportion of subjects with ES increased from 10 (50%) after a single hour of recording to 12 (60%) and 15 (75%) after two and three recordings, respectively. Extending the recording to 2 hours increased the yield of ES-positive patients from 6 (30%) to 8 (40%). In symptomatic patients there was excellent agreement between whether patients were positive for ES during each of two consecutive 1-hour recordings (kappa = 0.78, P = 0.0003) but poor agreement between the results of two single-hour recordings performed on different days (kappa = 0.22, P = 0.27). In asymptomatic patients, 4 (20%) were ES positive during the first hour; this increased to 5 (25%) after the recording was repeated once, with no further increase after the third recording. Extending the recording to 2 hours increased the yield from 3 (15%) to 7 (35%). In contrast to symptomatic stenoses, in patients with asymptomatic stenoses there was fair agreement between whether patients were ES positive on two consecutive 1-hour recordings (kappa = 0.49, P = 0.01) or two single-hour recordings performed on different days (kappa = 0.48, P = 0.02). Symptomatic subjects were more likely to have ES (when all 1-hour recordings were considered, 24/60 versus 10/60; P = 0.0046). ES in symptomatic subjects had a higher relative intensity increase than in asymptomatic subjects (P = 0.01). CONCLUSIONS: The temporal variability of ES needs to be taken into account in the design of optimal recording protocols and comparisons of results from different studies. Extending the duration of recording beyond an hour in symptomatic stenoses is of less value, but repeating the recording on a different day will often identify additional subjects with ES. In intervention studies in symptomatic patients, the time since last symptoms must be considered. In asymptomatic stenosis, extending the duration of recording beyond an hour will increase the proportion of patients positive for ES.

Adult↗
PubMed1998

Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study.

BACKGROUND AND PURPOSE: Embolism is believed to be the major cause of stroke in patients with nonvalvular atrial fibrillation (NVAF). The detection of asymptomatic embolic signals (ES) in individuals with NVAF might allow identification of patients at high risk of stroke and monitoring of therapy in individual subjects. We determined the frequency of asymptomatic ES in patients with NVAF who were not taking warfarin. METHODS: Bilateral transcranial Doppler recordings were made for 1 hour from the middle cerebral arteries of 111 successive patients with NVAF taking aspirin alone or no antithrombotic or anticoagulant therapy. Adequate recordings could be made in 86 patients. In 79 subjects, recordings were performed on a second occasion to study temporal variability. Recordings for a single hour were also made in 30 age-matched control subjects. RESULTS: ES were detected in 13 (15.1%) of NVAF subjects but in no control subjects (P=0.02). ES were detected both in subjects with symptomatic NVAF (4 of 30 [13.1%], P=0.04 versus controls) and asymptomatic NVAF (9 of 56 [16.1%], P=0.02 versus controls). There was no correlation between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, symptomatic status, left atrial size, left ventricular function, or the presence of left atrial thrombus detected on transthoracic echocardiography. Repeating the recording increased the number of patients with ES to 21 (26.6%). On considering the results of both recordings, again there was no association for either recording between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, age, symptomatic status, left atrial size, or left ventricular function. On repeating the recording, in the symptomatic group only 2 patients (8%) changed status, in contrast to 15 (29%) in the asymptomatic group. CONCLUSIONS: ES can be detected in patients with NVAF at a low frequency. Particularly in asymptomatic patients, ES show marked temporal variability. We found no correlation between the presence of previously reported clinical and echocardiographic markers of increased stroke risk and the presence of ES. This association requires further investigation before the clinical utility of this technique in patients with NVAF is decided.

Aged↗
PubMed1998

Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma.

BACKGROUND AND PURPOSE: The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in exon 7 of the eNOS gene (894G-->T) has been reported to be a strong risk factor for coronary artery disease. We determined whether it was also a risk factor for transient ischemic attack (TIA) and ischemic stroke and for carotid atheroma. METHODS: We studied 361 consecutive white patients presenting with ischemic stroke or TIA to a neurological cerebrovascular disease service and 236 normal white controls. In all patients CT and/or MR head imaging and high-resolution carotid duplex ultrasound were performed. The presence of the polymorphism (N/n) was determined by polymerase chain reaction and restriction with the enzyme BanII. RESULTS: There was no difference in the frequency of the NN genotype between patients and controls (13.0% versus 15.3%; P=0.44) or in N allele frequency (39% versus 37%; P=0.57). There was no association with genotype when only patients with stroke (excluding those with TIA) or when only individuals aged < or =65 years were considered. In contrast, there was a highly significant independent association between cerebrovascular disease and hypertension (odds ratio, 2.87; 95% CI, 2.0 to 4.15; P<0.00001), smoking (odds ratio, 2.58; 95% CI, 1.80 to 3.70; P<0.00001), and diabetes (odds ratio, 2.68; 95% CI, 1.38 to 5.24; P=0.004). There was no relationship between the polymorphism and any particular stroke subtype: large-vessel disease, for NN, 15 of 105 (14.3%); lacunar disease, 10 of 75 (13.3%); cardioembolic and unknown, 18 of 151 (11.9%); and tandem pathology, 4 of 30 (13.3%) (P=0.68, chi2). There was no difference in the mean degree of carotid stenosis between the 3 genotypes: NN, 31.1% (SD, 27.1); Nn, 30.1% (29.0); and nn, 31.2% (26.3) (P=0.9). There was no association between the NN genotype or the N allele and hypertension. CONCLUSIONS: We failed to find a relationship between this exon 7 polymorphism and ischemic cerebrovascular disease. In particular, it was not associated with stroke and TIA secondary to large-vessel atherosclerosis or with the degree of carotid stenosis in patients with cerebrovascular disease. It is unlikely that this particular polymorphism or any closely linked polymorphism is a major risk factor in the majority of white patients with stroke.

Aged↗
PubMed1997

Colour velocity flow measurement: in vitro validation and application to human carotid arteries.

Ultrasound measurement of volume blood flow is potentially useful for many clinical situations, yet practical implementation and use are restricted by the many instrumentation and blood flow limitations that can arise. Colour velocity imaging offers a number of theoretical advantages over methods based on duplex imaging. We evaluated a colour velocity flow measurement system (CVI-Q, Philips) both in a flow phantom and in vivo in the extracranial carotid arteries of normal volunteers. Over a range of constant (50-1200 ml/min) and pulsatile (92-366 ml/min) flows and using both steered and unsteered beams with beam angles of 30 degrees and 40 degrees, errors usually within 5% were obtained for constant flow and within 10% for pulsatile flow. However, with a beam angle of 70 degrees, higher errors of 20% were obtained for pulsatile flow. The reproducibility of flow measurements made using both anterior and posterior-lateral scanning approaches was determined in the common (CCA), internal (ICA) and external carotid (ECA) arteries of 18 volunteers. A greater reproducibility was found using the posterior-lateral approach (CCA 6.27%; ICA 9.8%), and mean (SD) flow values were 376 ml/min in the CCA and 255 ml/min in the ICA. The ratio of (ICA + ECA)/CCA flow calculated for each subject individually was mean (SD) 0.95 (0.11). Insonation from an anterior approach resulted in lower reproducibility and lower flow values. In conclusion, colour flow velocity imaging allows repeatable reproducible measurements of CCA and ICA flow, but results are optimal if a posterior-lateral scanning approach is used.

Blood Flow Velocity↗