Search PubMed⌕ Search

Biomedical subjects

M M Brown

Publications and source records attributed to M M Brown.

At least 91 records · Page 5Linked to original sources

Comparison of hemodynamic cerebral ischemia and microembolic signals detected during carotid endarterectomy and carotid angioplasty.

BACKGROUND AND PURPOSE: There has been concern about carotid percutaneous transluminal angioplasty (PTA) carrying a greater risk of cerebral ischemia than carotid endarterectomy. We set out to compare cerebral hemodynamics and microembolization during carotid PTA and CEA. METHODS: We used transcranial Doppler to monitor the middle cerebral artery of 28 patients undergoing carotid PTA (n = 14) or carotid endarterectomy (CEA) with a shunt (n = 14). Each period during which the internal carotid artery was occluded by PTA balloon or by clamp when the shunt was not in place was timed. Individual periods were summated to give a total occlusion time. Ischemic time was defined as the period for which mean middle cerebral artery velocity fell to a third or less of baseline. Microembolic signals were counted during each procedure. RESULTS: CEA resulted in significantly longer individual and total occlusion time than PTA (mean individual occlusion time, seconds), CEA, 168 +/- 51; PTA, 20 +/- 7; P < .001; mean total occlusion time; CEA, 337 +/- 70; PTA, 26 +/- 10; P < .001. Ischemic time was also significantly longer during CEA than during PTA (CEA, 165 +/- 40; PTA, 17 +/- 5; P = .001). There were significantly more microembolic signals during PTA than during CEA (mean number of microembolic signals during CEA, 52 +/- 64; during PTA, 202 +/- 119; P = .001). There was no correlation between any of the parameters measured and periprocedural stroke, which occurred in one patient in each group. CONCLUSION: PTA results in less hemodynamic ischemia but more cerebral microembolism than CEA. In this small series, however, it is not possible to comment on the relations between ischemic time, microembolism, and stroke.

Aged↗

Delayed improvement in carotid artery diameter after carotid angioplasty.

BACKGROUND AND PURPOSE: Carotid percutaneous transluminal angioplasty (PTA) is a new method of treating carotid artery stenosis. There has been concern about restenosis after carotid PTA. This study was performed to ascertain the change in percent stenosis 1 year after carotid PTA. METHODS: Twelve patients with symptomatic carotid stenosis were treated by PTA, and the anatomic result was studied by digital subtraction angiography at 1 year, supplemented by duplex ultrasound examinations at 1 month and 6 months. RESULTS: The mean severity of stenosis treated, measured by the common carotid method, was 82% (range, 69% to 98%). The immediate result of PTA was a reduction in the severity of stenosis in all patients to a mean of 51% (P<.005). Six of the 12 patients showed a further improvement in lumen diameter of > or = 14% at 1-year angiographic follow-up from a mean stenosis of 47% (range, 24% to 76%) immediately after PTA to 28% (range, 0% to 52%) at 1 year. This indicates an active process of remodeling in response to carotid PTA. PTA initially reduced the stenosis by > or = 20% in 9 of the 12 arteries, and 8 of these remodeled or remained largely unchanged compared with only 1 of the 3 with a suboptimal initial dilation. In 3 patients the lumen diameter improved by < 5%. Three other patients restenosed with an increase in stenosis after PTA of 9%, 16%, and 66% at 1 year, but all were asymptomatic. The duplex findings showed that remodeling occurred at variable times between PTA and 1 year. CONCLUSIONS: Remodeling of the carotid artery after PTA has not been described before. Our results confirm that carotid angioplasty has an acceptable patency rate at 1 year. It has been suggested that endovascular treatment of carotid stenosis should include placement of a stent. Our results indicate that this may not be necessary unless the initial PTA result is a reduction in stenosis of < 20%.

Aged↗

Genetic differences in nicotine-induced conditioned taste aversion.

Genetic differences in nicotine-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J, DBA/2J, BALB/cJ and C3H/heJ mice were adapted to a 2-h per day water access regimen. Subsequently, mice received nicotine injections (0.5, 1.0 or 2.0 mg/kg) immediately after 1-h access to a NaCl flavored solution. DBA and C3H mice developed dose-dependent aversions to the nicotine-paired flavor. BALB mice showed only minor reductions in intake with no difference between the nicotine dose groups. C57BL mice did not show development of nicotine-induced conditioned taste aversion. These results demonstrate that nicotine's aversion motivational effect is strongly influenced by genotype. Further, genetic sensitivity (DBA mice) or insensitivity (C57BL mice) to nicotine-induced conditioned taste aversion was similar to reports of genetic sensitivity to ethanol's aversive effect measured in this design.

Animals↗

The effect of suxamethonium on intracranial pressure and cerebral perfusion pressure in patients with severe head injuries following blunt trauma.

Eleven adult patients with severe head injuries caused by blunt trauma, (Glasgow Coma Score of eight or less after resuscitation), were studied while being mechanically ventilated and sedated in the intensive care unit (ICU). In a double blind randomized cross over trial each patient received a bolus of suxamethonium (1 mg kg-1) or an equal volume of saline (0.02 mL kg-1) before planned physiotherapy. Intracranial pressure (ICP) and mean arterial pressure (MAP) were measured continuously for 10 min after each injection. There were no significant changes in intracranial pressure or cerebral perfusion pressure (CPP) following the administration of suxamethonium or saline. Suxamethonium appears to be a safe drug to use on sedated persons with severe head injuries following blunt trauma.

Adolescent↗

Improvement in cerebral hemodynamics after carotid angioplasty.

BACKGROUND AND PURPOSE: Carotid percutaneous transluminal angioplasty ( PTA) may offer an alternative treatment to carotid endarterectomy. However, in contrast to carotid endarterectomy, which has been shown to normalize impaired cerebral hemodynamics, the effects of carotid PTA are unknown. Therefore, we prospectively studied the effect of carotid PTA on both perioperative and postoperative cerebral hemodynamics. METHODS: Eleven patients undergoing carotid PTA for symptomatic carotid artery stenosis were prospectively studied. Transcranial Doppler recordings from the ipsilateral middle cerebral artery (MCA) were performed during the procedure. In addition, MCA blood flow velocity and CO2 reactivity were determined before PTA and at 2 days, 1 month, and 6 months after procedure. The results were compared with those in 11 similar patients undergoing carotid endarterectomy in whom measurements were performed before and 1 month after the operation. RESULTS: During carotid PTA, in 2 of 11 patients during passage of the balloon catheter through the stenosis, MCA blood flow velocity fell transiently. In 6 of 11 patients there was a reduction in flow velocity (>50%) during balloon deflation, but this lasted only a few seconds. After the procedure there was a significant improvement in ipsilateral hypercapnic reactivity: preoperative value, 59.8+/-42.2% (mean+/-SD); 2 days, 77.9+/-31.4%; 1 month, 88.7+/-45.0%; 6 months, 89.8+/-33.9%; and (ANOVA P=.003) preoperative value versus 1 month, P<.02; versus 6 months, P<.02. In all cases in which reactivity was significantly impaired preoperatively, it returned to the normal range. Pulsatility index also increased significantly: preoperative value, 0.827+/-0.251 (mean+/-SD); 2 days, 0.992+/-0.262 (P=.002). Contralateral MCA hypercapnic reactivity also improved after carotid PTA. There was a similar improvement in ipsilateral hypercapnic reactivity after carotid endarterectomy. CONCLUSIONS: Carotid PTA results in a normalization of impaired hemodynamics, as assessed by CO2 reactivity. The degree of improvement is similar to that seen after carotid endarterectomy.

Angioplasty, Balloon, Coronary↗

CT muscle imaging and the clinical assessment of neuromuscular disease.

Twenty patients with neurogenic disorders, polymyositis, or muscular dystrophies were assessed clinically and by CT imaging of limb, limb girdle, and trunk muscles, using a standard protocol. On each side of these patients 26 movements were graded by the MRC scale, and 20 muscles were assessed by CT imaging. The clinical and CT findings could be compared, in a blind evaluation, in 10 muscles on each side. A quantitative assessment of the CT muscle images were also made. The CT images showed striking abnormalities, even in many muscles of normal strength by clinical testing. Asymmetrical involvement of muscles was found in all the disorders studied, even when not suspected on clinical examination. Muscles in patients with muscular dystrophy were more abnormal than those in patients with neurogenic disorders. In polymyositis the attenuation values were intermediate to the other two groups. A "washed-out" appearance with very low attenuation values was very suggestive of muscular dystrophy. Involvement of paraspinal and rectus abdominis muscles was uncommon in neurogenic disorders. The gracilis muscle was relatively resistant to degeneration. CT imaging can enhance the clinical assessment of patients with neuromuscular disease, often revealing unexpected abnormalities.

Amyotrophic Lateral Sclerosis↗

Asymptomatic cerebral embolic signals in symptomatic and asymptomatic carotid artery disease.

Transcranial Doppler ultrasound of middle cerebral arteries (MCAs) was used to detect asymptomatic embolic signals in a prospective study in patients with symptomatic and asymptomatic carotid stenosis. Recording from each artery for 20 min, embolic signals were more common ipsilateral to symptomatic arteries (eight of 38) than ipsilateral to asymptomatic arteries (one of 28, P = 0.04), or than in the MCAs of age-matched normal controls (none of 52, P < 0.005). Recording a subgroup of patients revealed that previously embolic-signal negative symptomatic stenoses frequently became embolic-signal positive when recording was repeated on another day. Including all recording periods (mean time: symptomatic 36.2 min, asymptomatic 46.2 min) embolic signals were detected ipsilateral to 13 of 38 symptomatic stenoses but only one of 28 asymptomatic stenoses (P = 0.003). In symptomatic subjects with embolic signals, median number of signals per hour was three (mean 26). One month following carotid endarterectomy embolic signals were not detected except in one patient who continued to experience frequent amaurosis fugax; in this patient following aspirin both symptoms and embolic signals were abolished. These studies suggest asymptomatic embolic signals correlate with clinical risk. Outcome studies are required to determine whether embolic signal detection may allow prediction of stroke risk and monitoring of the effectiveness of therapy. The technique may also prove useful in studying the pathophysiology of cerebral embolism.

Adult↗

The value of serological testing for Lyme disease in the UK.

Although the prevalence of Lyme disease (LD) in the UK is low, patients with clinical presentations compatible with the condition are common. Arthritis often complicates LD in North America, however it is a very rare complication of the condition in the UK. Many patients seen at St George's Hospital, London have visited endemic areas for LD within the UK, Europe and North America. To determine the value of serological testing for LD in the UK, we prospectively studied 120 patients seen at this hospital with clinical manifestations suggestive of LD (12 of whom were recruited to the LD clinic from outside the hospital catchment area), regardless of whether an alternative diagnosis seemed likely. A history of tick bite was obtained and serum antibodies to Borrelia burgdorferi detected initially by enzyme-linked immunosorbent assay (ELISA) and reactive samples immunoblotted to further assess antibody specificity. Tick bites were reported by 22 patients, 16 of whom were bitten in endemic areas for LD. A further 11 patients had exposure to tick habitats in endemic areas, but were unaware of a tick bite. Raised antibody levels were detected by ELISA in 14 individuals (seven of whom had a history of tick bite or tick exposure in an endemic area); however, only four of these had specific antibodies to B. burgdorferi confirmed on immunoblot. All of these four had a history of tick bite in an endemic area, all had arthritis and in three of the four, this was the only manifestation of the condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cerebral venous thrombosis and acquired protein S deficiency: an uncommon cause of headache in systemic lupus erythematosus.

A 42-yr-old woman with hypertension and renal involvement due to systemic lupus erythematosus (SLE) developed unilateral headache followed by the sudden onset of confusion and a grand mal convulsion. Cerebral computed tomography was normal. A magnetic resonance imaging angiogram revealed cerebral venous thrombosis and a venous infarct. Nephrotic syndrome had resulted in an acquired protein S deficiency. A review of previous cases suggests that either renal disease with proteinuria or features of the antiphospholipid syndrome are prerequisites for the development of cerebral venous thrombosis in SLE. Low free-protein S levels may be an additional risk factor. Furthermore it is likely that this condition is underdiagnosed.

Adult↗

Measurement of infarct size using MRI predicts prognosis in middle cerebral artery infarction.

BACKGROUND AND PURPOSE: An accurate measure of the severity of ischemic insult and the resulting prognosis is needed to assess the effectiveness of new treatments for acute stroke. We studied the reproducibility and accuracy of measurements of infarct volume with MRI and correlated the measurements with outcome. METHODS: Infarct volume was measured on T2-weighted images with the Analyze image analysis software. This technique was found to be highly accurate and reproducible. RESULTS: Measurements of infarct volume were found to be highly accurate and reproducible. Twenty-one patients (mean age, 66.5 years; range, 28 to 90 years) with cortical middle cerebral artery territory infarcts in whom adequate data could be obtained were studied within 72 hours from onset (mean delay to MRI, 27.5 hours; range, 5 to 72 hours). The Scandinavian Stroke Scale was used to calculate a prognostic score, and clinical outcome was assessed at 3 months. Infarct volume was found to significantly predict outcome. Mean infarct volume in the independent patients was 35.7 +/- 29.7 cm3 compared with 88.3 +/- 71.3 cm3 in dependent patients and 166.5 +/- 65.9 cm3 in dead patients (F = 10.52, P < .001). Patients with an initial infarct volume less than 80 cm3 were found to have a better outcome than those with larger infarct volumes. Secondary hemorrhage visible on MRI also predicted a poor outcome. In contrast, the Scandinavian Stroke Scale did not significantly predict outcome. CONCLUSIONS: The results demonstrate that measurement of the size of middle cerebral artery infarction with MRI is a useful tool in assessing prognosis and will have a valuable role in assessing new therapeutic agents.

Adult↗

Continuing ischemic damage after acute middle cerebral artery infarction in humans demonstrated by short-echo proton spectroscopy.

BACKGROUND AND PURPOSE: Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction. METHODS: Diagnostic MRI and short-echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months. RESULTS: Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N-Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N-acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period. CONCLUSIONS: The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

Adult↗

Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma.

BACKGROUND AND PURPOSE: A deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme gene has been associated with myocardial infarction. Its relations to both stroke and atheroma remain uncertain. We examined its role as a risk factor in patients with cerebrovascular disease and its relation to carotid atheroma. METHODS: One hundred one patients with symptomatic carotid artery territory cerebral ischemia were compared with 137 age-matched control subjects. In the patient group, carotid atheroma was assessed by measurement of degree of carotid stenosis and intima-media thickness with high-resolution duplex ultrasound. The D/I polymorphism was examined using the polymerase chain reaction. RESULTS: D:I allele frequency was 0.59:0.41 in case subjects and 0.48:0.52 in control subjects (P = .01). The DD genotype was more common in patients with cerebrovascular disease compared with control subjects (36/101 versus 30/137, P = .02). The DD genotype conferred a relative risk of any type of cerebrovascular disease of 1.98 (95% confidence interval [CI], 1.11 to 3.51; P = .02). However, this was largely due to a strong association in the 18 patients with lacunar stroke, in whom the D:I ratio was 0.75:0.25 (P = .0097 versus control subjects). The odds ratio for lacunar stroke associated with the DD genotype was 5.6 (95% CI, 2.0 to 15.7) and was still significant at 4.40 (95% CI, 1.45 to 12.6; P < .009) after controlling for other risk factors. There was no significant association between angiotensin-converting enzyme genotype and cerebrovascular disease due to large-vessel stenosis. There was no association between genotype and age, sex, smoking history, diabetes, or cholesterol level. CONCLUSIONS: The deletion polymorphism in the angiotensin-converting enzyme gene is a new independent risk factor for lacunar stroke but is not a risk factor for stroke associated with carotid stenosis.

Aged↗

Detection of asymptomatic cerebral embolic signals with Doppler ultrasound.

Can asymptomatic cerebral emboli be detected? With transcranial Doppler ultrasonography of the middle cerebral artery, short-duration high-intensity asymptomatic embolic signals were detected in 6 of 25 patients with carotid stenosis and in 9 of 24 with prosthetic cardiac valves, but not in 20 normal controls. In carotid stenosis the signals were usually unilateral and ipsilateral to the stenosis. Embolic signals were significantly more common in patients with mechanical valves than with pig xenografts (8/13 vs 1/11). With mechanical valves embolic signals were usually bilateral. Detection of asymptomatic emboli may allow identification of and preventive treatment in at-risk patients.

Aged↗

Additive binding of polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin to the murine hepatic Ah receptor.

Fixed aliquots of both radiolabeled [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hepatic Ah receptor from C57BL/6J mice were incubated competitively at 4, 23, and 30 degrees C with mixtures of 2,3,7,8-TCDD and several polychlorinated biphenyls (PCBs). The production of the radiolabeled receptor-ligand complex changed if the ligands were added sequentially, demonstrating that the competition between PCBs and TCDD for the Ah receptor in vitro is principally a kinetic rather than an equilibrium phenomenon and is irreversible on the time scale of our in vitro experiments. Examination of previous reports on the ability of TCDD, PCBs, and their mixtures to induce cleft palate in fetal mice suggests that the potency of receptor-ligand complexes is ligand-dependent. Receptor occupancy is not a sufficient condition for toxicity, and protection by one ligand against the toxic effect of a second, more potent one is only possible when a significant fraction of receptors is occupied.

Animals↗

Detection of circulating cerebral emboli using Doppler ultrasound in a sheep model.

We describe a validation study of a new technique for detecting circulating pathological cerebral emboli. Theoretically one would expect solid emboli to be detectable as high intensity signals on the Doppler waveform, and such signals have been reported in humans with potential embolic sources. Pathological cerebral emboli (thrombi, platelet aggregates and atheroma) were introduced into the proximal carotid artery of an in vivo sheep model, and their passage detected in the cerebral circulation using Doppler ultrasound. All of 74 emboli, with a maximum dimension as small as 0.24 mm, were detected as short duration high intensity signals. Smaller pathological emboli could not be made but glass microspheres as small as 5-20 micron resulted in high intensity signals. A significant positive correlation was found between embolus size and relative intensity increase of the embolic signal. A significant positive correlation was also found between embolus size and duration of embolic signal. This study demonstrates that detection of circulating cerebral emboli is possible in vivo. This technique may allow selection of patients at particularly high risk of cerebral embolisation so that they can be given specific prophylactic treatment. Analysis of the Doppler signal may give information on the size of the embolus, although using current signal analysis it is impossible to distinguish between the signals produced by say a larger platelet embolus or a smaller thrombus embolus.

Animals↗

Rhythmic oscillations with a wavelength of 0.5-2 min in transcranial Doppler recordings.

We have studied intracranial pressure (ICP) B-waves and their association with rhythmic changes in blood flow velocity (B-wave equivalents) by transcranial Doppler sonography (TCD) monitoring. In overnight TCD recordings in 10 normal young adults, these rhythmic changes in blood flow velocity were higher and more frequent during REM sleep and sleep stage 1 than during other sleep stages. B-wave equivalents also had a longer wavelength during REM sleep. Their relative frequency in these normal subjects over one night ranged from 35 to 73%. Peripheral resistance (assessed by the Pourcelot index) was lower and heart rate was higher at the peak of these oscillations. These results support the hypothesis that ICP B-waves are caused by vasodilation. A non-linear relationship between ICP and blood flow velocity was found during B-waves in 9 of 11 patients with suspected NPH. Our results throw doubt on the suggestion that a relative frequency of less than 80% B-wave activity can be a valid indicator for shunt responsiveness in patients with suspected normal pressure hydrocephalus (NPH). ICP recordings in suspected NPH should be accompanied by polysomnography to avoid misleading results due to variability of B-wave appearance dependent on sleep pattern.

Adult↗