Biomedical subjects
Publications and source records attributed to J Biller.
This report presents data from pilot studies of Org 10172 in the management of patients with acute ischemic stroke. The studies have established a potentially optimal dosage and treatment regimen and have provided information for the development of a large randomized trial. The trial of Org 10172 in acute stroke treatment is now underway in the United States.
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the prevalence of coronary artery disease and coronary events during follow-up in patients with asymptomatic carotid stenosis, transient ischemic attacks, or small strokes. METHODS: We prospectively studied 60 consecutive patients with thallium-201 scintigraphy followed by coronary arteriography according to an established protocol. RESULTS: The 201Tl testing was abnormal in seven of 15 patients (47%) with asymptomatic carotid stenosis and in 19 of 44 patients (43%) with transient ischemic attacks or small strokes (p greater than 0.05). In 33 patients with no history of coronary artery disease, 11 (33%) had reversible 201Tl defects. In 26 patients with a history of coronary artery disease, 15 (58%) had reversible and/or fixed defects (p = 0.054 compared with patients with no history). A history of peripheral vascular disease was the only risk factor significantly associated with an abnormal 201Tl test (p = 0.032). Coronary artery stenosis of greater than 50% was identified in one or more vessels in 14 of 15 patients undergoing coronary arteriography. Over a mean follow-up period of 311 days, four patients (7%) developed new onset of angina. There were four coronary events among 14 patients (29%) with both a reversible area on the 201Tl and abnormal coronary arteriography. In comparison, there were only four coronary events among 46 patients (9%) without reversible defects on the 201Tl studies (p = 0.055). CONCLUSIONS: Our study demonstrates that one third of patients with no history of coronary artery disease had an abnormal 201Tl test and that nearly one half of patients with either symptomatic or asymptomatic cerebrovascular disease had abnormal 201Tl tests. Patients with a reversible 201Tl defect and significant stenosis by coronary arteriography were at higher risk for subsequent cardiac events. These findings demonstrate the utility of screening patients with asymptomatic and symptomatic cerebrovascular disease for cardiac disease.
Pulmonary arteriovenous malformations occur in 15-20% of patients with Rendu-Osler-Weber syndrome and can be the source of paradoxical emboli causing cerebral ischemia, septic emboli leading to brain abscesses, or polycythemia causing hyperviscosity and cerebral ischemia. The diagnosis of these malformations may be elusive, since classic clinical or radiologic findings may be absent in some patients. The authors report a patient with Rendu-Osler-Weber syndrome with cerebral ischemia who had normal findings from a pulmonary examination and chest roentgenogram. An ultrafast computed tomography scan of the chest demonstrated, however, a pulmonary arteriovenous malformation in the right upper lobe that was successfully resected. Ultrafast computed tomography of the chest is a relatively noninvasive method of screening for a pulmonary arteriovenous malformation in a patient with Rendu-Osler-Weber syndrome and otherwise unexplained neurologic symptoms.
Several ongoing studies are evaluating the optimal management of patients with cerebrovascular disease. The Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin (CASANOVA) study has shown that carotid endarterectomy is not recommended for asymptomatic patients with less than 90% carotid stenosis. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgical Trial (ECST) have demonstrated that endarterectomy should be considered for patients who had recent carotid artery territory ischemic symptoms associated with angiographically defined stenosis of greater than 70%. These and other trials are expected to provide further data regarding management of cerebrovascular disease, including treatment of those patients with moderate (30 to 69%) carotid stenosis. Until that time, treatment decisions must be made on a case-to-case basis.
Ischemic stroke is a major cause of death and disability. Despite its high incidence, acute management remains controversial. Most current forms of therapy are designed to reduce complications of a recent stroke or prevent recurrences. Experimental data suggest that the optimal time for intervention is the hour immediately following brain ischemia.
The role that stroke patients have played in the history of behavioral neurology was illustrated by describing some contributions made by Broca, Dejerine, Wilbrand, Liepman, and Geschwind. The recent work on the anatomic basis of recovery or lack of recovery in aphasia was discussed and the network of structures important in attention were reviewed. The study of stroke patients with amnestic syndromes (particularly those with basal forebrain and diencephalic lesions) was discussed as well. Starting with Liepman's classic contribution, and then looking at more recent studies, the left hemisphere's role in limb praxis was analyzed. The different syndromes that result when the superior and inferior visual association cortices are damaged were described and illustrated. A summary of neurobehavioral syndromes related to stroke that may present to the psychiatrist because the patient does not have an hemiparesis was given. The relationship of stroke to dementia and depression was reviewed.
Cerebral vasculitis may occur in isolation or in conjunction with a systemic illness. Although a relatively infrequent cause of intracerebral or subarachnoid hemorrhage, it should be considered in a setting of relevant systemic symptoms, an unexplained progressive neurologic disorder, or in a patient lacking risk factors for hemorrhagic stroke. Diagnosis may be difficult because the results of most studies may be normal or nonspecific. Because treatment is effective in many of the cerebral vasculitides, vigorous pursuit of the diagnosis is warranted.
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We describe two adult patients who presented with acute cerebral infarction and were found to have a hypercoagulable state due to nephrotic syndrome. One patient had a deficiency of free protein-S. The other patient had a pulmonary embolus 4 months after the stroke. Our cases demonstrate that the hypercoagulable state associated with nephrotic syndrome can be associated with cerebral arterial thrombosis and infarction in adults. Examination of the urine remains an important part of the evaluation of patients with recent stroke. The presence of severe proteinuria and a low serum albumin content should prompt consideration of a hypercoagulable state. Our experience suggests that anticoagulant drugs may be required to reduce the risk of new thrombotic events.
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To determine the risk and time to cerebrovascular complications with idiopathic hypertrophic subaortic stenosis, we studied 119 patients (66 men and 53 women) with evidence of this disease based on strict echocardiographic criteria and followed them up for a mean +/- SEM of 6.5 +/- 0.6 years. Cerebral ischemic events occurred in 26 patients (22%), and in five patients stroke was the initial presenting event. Men had cardiac symptoms at a younger age than women, but there was no significant difference in age at the time of stroke. Cardioembolic cerebrovascular events were associated with atrial fibrillation and left atrial enlargement, whereas atheroembolic events were associated with hypertension. An increased risk of stroke was associated with female sex, mitral anulus calcification, hypertension, and atrioventricular conduction delay. Unlike most previous series, this study shows that patients with idiopathic hypertrophic subaortic stenosis may present with stroke.
A case in which an aneurysm of the proximal descending thoracic aorta was the likely source of retrograde cerebral embolism is described. Atherosclerotic disease of the descending thoracic aorta should be considered as an unusual source of cerebral emboli.
We reviewed the one-month mortality among 213 patients aged fifteen to forty-five years (mean thirty-five) with acute cerebral infarction (CI) evaluated during the period July 1, 1977, to February 1, 1988. Atherosclerotic cerebral infarction (ACI) was diagnosed in 59 (27.7%) patients, 53 (24.9%) had non-atherosclerotic vasculopathies (NAV); 46 (21.6%) had cardioembolic infarcts (CEI). Hematologically related disorders were diagnosed in 30 (14.1%) patients; the cause of CI could not be established in 25 (11.7%) patients. Fourteen patients (9 men, 5 women, mean age 34.8 years), (6.6%) died within thirty days of their CI: 7 had CEI (7/46,15.2%); 4 had ACI (4/59, 6.7%); and 3 had NAV (3/53, 5.6%). Our data suggest that young patients with acute CI have a thirty-day mortality rate lower than older patients. Deaths were most common in patients with CEI. Brain edema and herniation accounted for 6 (43%) of the deaths.
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Stroke ranks third as a cause of death in much of the industrial world, surpassed only by heart disease and cancer. Thrombotic and embolic arterial occlusions are the leading causes of cerebral infarction. Once a major cerebral infarction has occurred, therapy is limited to the prevention of complications and rehabilitation. Identification and treatment of stroke-prone patients are now not a standard part of medical practice. However, the proper management of the patient with acute cerebral ischemic or progressing stroke is a subject of debate. Treatment of progressing or acute cerebral ischemia is aimed at prevention of infarction in areas of the brain that are still viable. A number of therapeutic strategies are currently being investigated in the management of ischemic stroke.
To assess the impact of cigarette smoking on stroke in young adults (15 to 45 years old), we compared smoking data from 181 patients with cerebral infarction with that of 307 control subjects matched for age, gender, geographic location, and hospital admission dates. While controlling for these matching variables and hypertension, an analysis based on a conditional logistic regression model indicated that a smoker was 1.6 times more likely to have a cerebral infarction than a non-smoker (95% confidence interval, 1.07 to 2.42). There was a cumulative dose effect with each additional pack-year causing a greater risk of having a cerebral infarction. In fact, after adjusting for all other risk factors, there was a significant quadratic component to the dose-response relationships, with the result that individuals with a larger number of pack-years were invariably the stroke patients. There was no significant difference in smoking status among the various subtypes of cerebral infarction (atherosclerotic, nonatherosclerotic vasculopathy, cardioembolic, hematologic related, undetermined). These data indicate that cigarette smoking is an important risk factor for cerebral infarction in young adults. Risk factor modification through cessation of smoking may reduce the risk of ischemic stroke in young adults.
A circadian pattern for the onset of myocardial and cerebral infarction has been identified. To evaluate this phenomenon further, we analyzed prospectively collected data from 151 patients with acute ischemic stroke. The number of strokes per 6-hour period were the following: midnight to 6 AM, 20 (13%); 6 AM to noon, 86 (57%); noon to 6 PM, 21 (14%); and 6 PM to midnight, 24 (16%). This pattern was not affected by previous use of aspirin. The most frequent time of onset was 6 AM to noon for all subgroups of ischemic stroke: small artery, 71%; cardioembolic, 62%; large artery atherothrombotic, 57%; large artery atheroembolic, 46%; and "other" or unknown cause, 40%. We also investigated the time between awakening and stroke onset in 145 patients and found that 24% of ischemic strokes occurred within the first hour after awakening. Our data demonstrate that an early morning peak exists for all subtypes of stroke. Our data also suggest that the most critical period is the first hour after awakening.
Coronary artery disease and ischemic cerebrovascular disease are leading causes of morbidity and mortality in the United States. Coronary artery disease often coexists with asymptomatic carotid artery atherosclerosis, transient ischemic attacks, or ischemic stroke. Numerous studies have shown that mortality from all forms of ischemic cerebrovascular disease is primarily due to coronary artery disease. Thus, there is increasing interest in identifying coronary artery disease in patients with cerebrovascular disease, including those without clinical manifestations of heart disease. We review the use of current noninvasive techniques to detect coronary artery disease and present practical approaches to screen for ischemic heart disease. Current diagnostic imaging methods for potential cardioembolic sources of cerebral infarction are also discussed.