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Biomedical subjects

P D Lyden

Publications and source records attributed to P D Lyden.

At least 37 records · Page 2Linked to original sources
PubMed1997

Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

OBJECTIVE: To develop an approach for reducing time between emergency department (ED) admission and treatment in patients with acute ischemic stroke to meet the challenge of providing tissue plasminogen activator treatment within 180 minutes. DESIGN: An observational study. SETTING: Forty trial-affiliated hospitals, including 30 community hospitals. PARTICIPANTS: A total of 17,324 consecutive patients admitted to trial-affiliated hospital EDs within 24 hours of possible stroke, from January 1991 through October 1994. INTERVENTION: Appraisal of the process of triage, evaluation, diagnosis, and treatment by means of total quality improvement techniques in each hospital. Staff participating in the process identified sources of variation and modifications by flow charting the process. MAIN OUTCOME MEASURE: Time between ED admission and treatment with study medication. RESULTS: Total quality improvement methods identified hospital-specific process improvements. Many improvements were administrative, requiring no additional resources. More than 50% of screened patients arrived too late to be treated. Only 1268 patients were admitted between 0 and 125 minutes from stroke onset with no other trial exclusion criteria; 48% were treated. Of 243 patients admitted between 126 and 170 minutes from stroke onset with no exclusion criteria, 4% were treated. Mean time from ED admission to treatment was similar in teaching and community hospitals. CONCLUSIONS: Total quality improvement methods identified ED-specific sources of process variability and reduced time between ED admission and treatment. Therefore, these methods should be considered in developing and monitoring emergent stroke treatment protocols.

Acute Disease↗
PubMed1997

High dose baclofen is neuroprotective but also causes intracerebral hemorrhage: a quantal bioassay study using the intraluminal suture occlusion method.

Agonists of the GABA-A receptor are neuroprotective after experimental stroke, but studies of GABA-B agonists have contradicted each other. To further investigate whether GABA-B agonists may be neuroprotective, we devised a quantal bioassay using the intraluminal occlusion method of inducing reversible cerebral ischemia. Subjects underwent middle cerebral artery occlusion for varying amounts of time, ranging from 5 to 90 min. Behavioral outcome was measured 48 h later with a quantal observational scale: score of abnormal given for any one of asymmetric forepaw flexion on tail lift, asymmetric grip, circling, reduced exploration, seizures, or death. To the grouped response data the logistic equation was used to find the ED50, the duration of occlusion that caused one-half of the subjects to be abnormal. To find the potency ratio for each drug, we divided the ED50 for treatment by that for vehicle. We administered baclofen, a GABA-B agonist, intraperitoneally 5 min after the onset ofischemia. Baclofen (20 mg/kg) was neuroprotective (potency ratio of 3.0, P < 0.05), but a lower dose (10 mg/kg) was not. However, both doses of baclofen caused significantly more intracerebral hemorrhages than control. In awake animals, both baclofen doses caused significant increases in mean arterial pressure, but no changes in other cardiorespiratory variables. The glutamate antagonist MK-801, the GABA-A agonist muscimol, and hypothermia were all protective using the bioassay (potency ratios ranging from 1.5 to 3.0). We conclude that although baclofen (20 mg/kg) may be neuroprotective, its utility is complicated by postischemic hypertension and cerebral hemorrhages.

Animals↗
PubMed1997

Effect of ischemic cerebral volume changes on behavior.

Ischemia causes long-term effects on brain volume and neurologic function but the relationship between the two is poorly characterized. We studied the relationships between brain volume and three measures of rodent behavior after cerebral ischemia was induced by injecting several thousand microspheres into the internal carotid arteries of rats. Forty eight hours later, each subject was rated using a global neurologic rating scale. Several weeks later, the subjects were tested for open field activity and visual spatial learning. Post-mortem we measured the volume of the cerebral hemispheres and estimated the volume densities of cortex, white matter, hippocampus, basal ganglia, thalamus, ventricle, and visible infarction. Ischemia caused significant impairment, as measured by the global rating scale; the probability of an abnormal rating was correlated with the number of microspheres trapped in the brains. Visual spatial learning was significantly impaired by ischemia, but this deficit was independent of the count of microspheres, whether the subject was abnormal at 48 h, and whether the left or right hemisphere was embolized. Cerebral hemisphere volume was reduced from 430 mm3 to 376 mm3 (P < 0.05). The cortex was reduced from 22 to 19% of cerebrum (P < 0.05) and the white matter compartment was reduced to similar degree. The lesion volume was 6% of cerebrum, comparable to that seen with other ischemia methods. The global outcome rating was significantly related to total cerebral volume, but not to volume changes in any single compartment. On the other hand, visual spatial learning was significantly influenced by volume changes in the cortex and white matter, but not by the topography of the visible infarctions. Open field activity was not altered by infarction. Our data suggests that the total volume of brain tissue lost to infarction may partially determine global neurological rating independently of the topography of the volume loss. Integrative functions such as learning may depend more on the integrity of specific compartments and less on the total volume of intact brain. The volume of visible cystic infarction was not related to long term behavioral outcome. These results should be confirmed using another method of inducing ischemia.

Animals↗
PubMed1997

Visualization of the cerebral circulation using three-dimensional transcranial power Doppler ultrasound imaging.

The purpose of this study was to evaluate the anatomy of the cerebral circulation, particularly the circle of Willis, using three-dimensional ultrasound (3DUS) imaging. Image data were obtained through the right transtemporal window from 8 young, healthy volunteers by acquiring gray-scale and color Doppler spectral (CDI) and energy (CDE) images using two-dimensional ultrasound equipment with a 2-MHz probe. Images and transducer position coordinates were fed into a graphics workstation, reprojected, analyzed to extract the blood flow signal, volume rendered, and displayed interactively. The architecture of the cerebral circulation was evaluated from multiple orientations using stereo viewing glasses and rotation to enhance the understanding of vessel position. The primary vessels of the cerebral circulation including the circle of Willis and bilateral views of the branching arteries (middle, anterior, and posterior cerebral arteries and internal carotid artery) could be imaged readily with 3DUS through one transtemporal window. Acquisition time was typically less than 30 seconds. Volume-rendering methods greatly assisted in showing the overall spatial relationships and continuity of cranial vessels. Secondary branches of the cerebral arteries were seen in 2 patients. Color data from two-dimensional ultrasound imaging that otherwise might be identified as artifact was found to represent continuous small vessels on three-dimensional viewing. 3DUS facilitates imaging of cranial vascular anatomy by clarifying overall spatial relationships and enhancing comprehension, compared to two-dimensional ultrasound methods. The method is rapid and the circle of Willis can be visualized from one side of the head.

Brain↗
PubMed1997

Medical therapy for intracerebral hematoma with the gamma-aminobutyric acid-A agonist muscimol.

BACKGROUND AND PURPOSE: No therapy has been rigorously proven effective for intracerebral hematoma, although surgery is frequently used for some types of lobar hemorrhages. Since intracerebral mass causes significant ischemia in surrounding brain, we reasoned that anti-ischemia therapy might improve outcome after experimental hematoma. METHODS: We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats. Four hours later we administered intravenously 2 mg/kg muscimol, a potent agonist of the gamma-aminobutyric acid-A receptor (n = 20); 1 mg/kg MK-801, an antagonist of the N-methyl-D-aspartate receptor (n = 17); or saline (n = 28). Forty-eight hours after collagenase injection we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase by the quantal bioassay procedure. Brains were then prepared for histomorphometry and brain volumes estimated. RESULTS: We found that the ED50 for collagenase (amount of enzyme that renders 50% of the subjects abnormal) was 0.77 +/- 0.09 U in saline-treated subjects. Treatment with muscimol significantly increased the ED50 to 1.2 +/- 0.21 U, for a potency ratio of 1.55 +/- 0.34 (t = 1.7, P < .05). MK-801 did not affect outcome. Volume of hematoma was significantly correlated with amount of injected collagenase (n = 33, r = .64, P < .001). Volumes of basal ganglia and white matter were significantly reduced by hemorrhage, and muscimol partially ameliorated this. CONCLUSIONS: We conclude that muscimol significantly improves neurological outcome after intracerebral hematoma.

Animals↗
PubMed1995

Impact of race and ethnicity on ischemic stroke. The University of California at San Diego Stroke Data Bank.

BACKGROUND AND PURPOSE: As the US minority population continues to grow, increasing numbers of nonwhite citizens are at risk for stroke. A better understanding of how ischemic stroke differs in the minority populations may lead to more effective clinical management. METHODS: We prospectively evaluated 542 consecutive patients (416 whites, 71 Mexican Americans, 55 blacks) presenting to the University of California at San Diego Medical Center or the San Diego Veterans Affairs Hospital with presumed acute ischemic stroke or transient ischemic attack. RESULTS: Whites had a higher proportion of transient ischemic attacks (32% versus 18% and 17% for blacks and Mexican Americans, respectively) and had the lowest prevalence of diabetes mellitus (17% versus 29% and 40% for blacks and Mexican Americans, respectively). Mexican Americans had higher initial serum glucose levels (178 versus 133 and 131 mg/dL for whites and blacks, respectively). Blacks were youngest (average age, 56 years). There were no differences among the groups in the prevalence of prior stroke, hypertension, myocardial infarction, or smoking; initial systolic blood pressure, serum cholesterol levels, and functional deficit also were similar. Although it did not reach statistical significance, there was a trend toward relatively late presentation in the black stroke subpopulation: only 53% of blacks (compared with 73% of both Mexican Americans and whites) reached medical attention within 24 hours of stroke onset. All groups had similar diagnostic evaluations and functional outcome at 1 week. With the exception of a higher frequency of stroke of unknown cause in Hispanics, the distributions of stroke etiologies did not differ significantly among the groups. CONCLUSIONS: These data suggest that there are significant clinical differences in populations with ischemic stroke and transient ischemic attack that are related to race and ethnic origin, but in our population these differences did not include the extent of diagnostic evaluation undertaken or stroke severity.

Acute Disease↗
PubMed1995

Spontaneous early improvement following ischemic stroke.

BACKGROUND AND PURPOSE: Recognizing that early spontaneous neurological improvement not uncommonly follows acute ischemic stroke, we conducted this study to determine the incidence of such improvement and its potential relation to stroke etiology. METHODS: We prospectively evaluated 68 patients who presented within 12 hours after ischemic stroke, exhibited moderate or severe new functional neurological deficit acutely, and received either no stroke-specific therapy or only antiplatelet therapy over the ensuring week. We reexamined all patients 1 week after stroke onset. RESULTS: Sixteen (24%) of the 68 patients improved to the point of having no or mild functional neurological deficit at 1 week. Patients with lacunar stroke were more likely to enjoy early spontaneous improvement (8/22 = 36% versus 8/46 = 17%), but this difference did not reach statistical significance (P = .15). CONCLUSIONS: Early spontaneous improvement after ischemic stroke may occur in a substantial proportion of patients and more commonly after lacunar stroke. Even so, the majority of patients with acutely disabling stroke will remain significantly impaired 1 week after stroke onset.

Cerebrovascular Disorders↗
PubMed1995

Gait parameters following stroke: a practical assessment.

Mechanical methods of quantifying gait are more sensitive to change than is direct clinical inspection. To assess gait parameters and patterns of patients with stroke, and the temporal changes of these parameters, a foot-switch gait analyzer was used to test 49 ambulatory patients with stroke and 24 controls. Patients walked significantly slower than controls, with decreased cadence, increased gait cycle, and increased time in double limb support. Patients' hemiplegic limbs spent more time in swing and stance when compared to controls; their unaffected limbs spent significantly more time in stance and single limb support compared to controls. Patients' hemiplegic side, when compared with the unaffected side, spent less time in stance and more time in swing. A flatfoot pattern was typically noted on the affected side. General gait parameters improved over time, with the largest changes occurring in the first 12 months. However, the percentage of time spent in double and single limb support, stance and swing, parameters which describe the asymmetrical pattern of gait, did not change over time. Abnormal gait was due to difficulty in moving the body over an unstable limb. Gait analysis can be of importance in documenting abnormalities and determining the effects of therapeutic modalities.

Adult↗
PubMed1994

Combination therapy protects ischemic brain in rats. A glutamate antagonist plus a gamma-aminobutyric acid agonist.

BACKGROUND AND PURPOSE: The excitotoxic effects of glutamate can be blocked almost completely with gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, in cell culture, tissue slices, and in some animal models. After stroke in rats, we showed previously that an agonist of GABA, muscimol, was as neuroprotective as MK-801, an antagonist of glutamate. To obtain further neuroprotection and to avoid the side effects associated with high doses of MK-801, we wanted to assess the efficacy of the two agents in combination. METHODS: Treatment was administered 5 minutes after embolic cerebral ischemia in Sprague-Dawley rats. The subjects were rated using a neurological evaluation 48 hours later. Visual-spatial learning was measured 8 to 10 weeks after stroke, after which we measured the volume of each cerebral hemisphere and several large cerebral compartments. Treatment groups included saline (n = 27), MK-801 1.0 mg/kg (n = 23), muscimol 1.0 mg/kg (n = 17), and both agents together using a dose of 0.5 mg/kg each (n = 25). RESULTS: A probit analysis of the neurological ratings revealed a protective effect of muscimol used alone (MK-801 potency ratio, 2.0; P = NS; muscimol potency ratio, 4.0; P < .05) and a protective effect of the combination (potency ratio, 5.0; P < .05). Focal ischemia caused a moderate to severe delay in the acquisition of visual-spatial information, which was completely eliminated by the combination treatment but only partially ameliorated with MK-801 or muscimol alone. Ischemia reduced the cerebral hemisphere volume from 0.42 mm3 to 0.34 mm3 (P < .0001), the volume density of cortex from 22% to 17% of total cerebral volume (P < .01), and that of hippocampus from 4.3% to 3.0% (P < .05). Only the combination was neuroprotective, as measured by the ratio of the lesioned to the contralateral hemisphere volume (P = .013). The combination treatment and MK-801 protected the hemisphere volume, the cortex, and the hippocampus and reduced the size of visible infarction. CONCLUSIONS: Combination therapy, using a glutamate antagonist and a GABA-A agonist, appeared to protect the brain and ameliorate a defect in learning behavior after stroke. The combination may have been more effective than either agent used alone, although further study of higher doses is needed.

Animals↗
PubMed1994

A rapid, reliable, and valid method for measuring infarct and brain compartment volumes from computed tomographic scans.

BACKGROUND AND PURPOSE: Clinical stroke trials require objective and reproducible end point variables. Morphometry of cerebral structures, including infarct volume, provides numerical measures that represent the amount of tissue damaged and potentially salvaged by therapy. However, morphometry may be time-consuming and labor-intensive, and it requires standardization across multiple centers, which may be difficult to achieve in large multicenter trials. We developed a brain morphometry method that is unbiased, rapid, reliable, and based on well-accepted stereological techniques. We now extend this method to analysis of routine computed tomographic (CT) scans such as might be obtained during a clinical stroke trial. METHODS: We studied CT scans from 18 stroke patients and 14 asymptomatic control patients obtained over 5 years at the San Diego Veterans Administration Medical Center. Three observers independently measured the volume of the cranial vault, cerebrum, cortex, white matter, deep gray structures, ventricle, sulcal cerebrospinal fluid space, visible infarction, and cerebellum/brain stem. RESULTS: The two patient groups were well matched demographically. The intracranial volume of 1400 +/- 40 mL in control subjects was not different from the 1311 +/- 41 mL in patients. Cerebral volume was 1250 +/- 36 mL compared with 1070 +/- 36 mL (control subjects versus patients, P < .001), and infarction volume was 55 +/- 16 mL in patients. For all structures, intraclass correlation coefficients among the observers ranged from 0.87 to 0.03; the best agreement was found for lesion, ventricle, and intracranial volume. White matter and cortex volume predicted the National Institutes of Health Stroke Scale score but not the late outcome scores on the Barthel Index or Rankin Scale. Each scan required 70 to 90 minutes for analysis. CONCLUSIONS: We developed a stereological method for cerebral morphometry from CT scans that is reliable, rapid, and simple. The measurements are unbiased, can be made on slices of any known thickness, and are independent of machine variables. Our results are remarkably similar to values obtained with more labor-intensive methods. This method should be of use in large-scale, multicenter trials of stroke therapy.

Aged↗
PubMed1993

An analysis of ischemic stroke in an urban southern California population. The University of California, San Diego, Stroke Data Bank.

BACKGROUND: Stroke databanks may provide important information regarding regional and temporal variations in the causes of stroke. METHODS: Five hundred consecutive patients presenting to the University of California, San Diego, stroke services with acute ischemic stroke were evaluated prospectively. A specific cause of stroke was assigned in each case according to predetermined diagnostic criteria. RESULTS: Relative incidences of ischemic stroke causes were as follows: lacunar, 27%; unknown cause, 23%; cardioembolic, 22%; large-vessel atherothrombotic/embolic, 18%; and miscellaneous, 10%. CONCLUSIONS: These relatively high rates of lacunar stroke and stroke of unknown cause are similar to those from other recent surveys and may reflect an important shift in the pathophysiologic mechanisms that underlie ischemic stroke.

Adolescent↗
PubMed1993

Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence.

Hemorrhagic infarction and cerebral hematoma are feared events that may follow cerebral ischemia. Newly developed thrombolytic agents may be effective stroke therapy, but may also promote hemorrhagic complications after ischemic stroke. It is therefore critically important to understand the true incidence of hemorrhagic transformation after ischemic stroke, and to identify if possible the mechanisms underlying the phenomenon. In recent years, studies using serial computed tomography to identify hemorrhage have shown that transformation occurs in 15 to 43% of patients presenting with ischemia. Experimental and clinical evidence support the notion that hemorrhage results from augmented collateral circulation into the ischemic zone, perhaps in concert with hypertension. Recanalization and distal migration of the thrombus are not factors that are associated with transformation. Pharmacologic recanalization using thrombolytic drugs are not likely to be associated with hemorrhage if reperfusion is accomplished very soon after the onset of neurologic symptoms.

Brain Ischemia↗
PubMed1992

Quantitative effects of cerebral infarction on spatial learning in rats.

Outcome following stroke is difficult to measure because the behavioral response to infarction is variable. We hypothesized that cognitive function, such as spatial learning, may be a reproducible and sensitive outcome variable. We developed an animal model of multifocal cerebral ischemia in order to study the effects of infarction on learning. To cause ischemia, several hundred microspheres were injected into the internal carotid arteries of rats. After ischemia, behavior was measured using a global rating and a Morris water maze. Postmortem serial brain sections were stained and the size of the infarctions was measured. We found that intracerebral microspheres caused cortical infarction and an impairment of spatial learning. This impairment was not due to occlusion of the internal carotid artery and was not found in animals who received a sham injection of saline. The degree of learning impairment was not correlated with the volume density of the infarctions or with the volume density of the remaining cerebral hemisphere. The learning impairment clearly differentiated normal from lesioned animals, and the impairment was probably due to a delay in acquisition of spatial information rather than a defect in retention or retrieval. Measurement of learning deficit after cerebral ischemia is an efficient and sensitive method for evaluating new stroke treatments and possibly for exploring structure function relationships.

Animals↗