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Biomedical subjects

A Alavi

Publications and source records attributed to A Alavi.

At least 19 recordsLinked to original sources
PubMed1992

Positron emission tomography in cerebrovascular disorders.

The introduction of positron emission tomography (PET) as a powerful imaging modality has played a major role in the understanding of the pathophysiological bases for cerebrovascular disorders. PET is the only technique that allows measurement of regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen and glucose metabolism with detail and accuracy. Using PET, these physiological parameters can be measured to determine the extent of the disease from the early stages of cerebrovascular disorders to acute cerebral infarction. Significant hemodynamic and metabolic abnormalities are noted in chronic ischemia, but no structural changes are noted on anatomic images. PET studies have shown that in many patients in the early phases (10 to 12 hours) of clinically diagnosed acute stroke, a substantial area of ischemia exists, which, if untreated, will become irreversibly damaged. Similar to the results achieved in patients with acute myocardial infarction, appropriate intervention in patients with cerebrovascular disorders may significantly reduce the extent of injury to the brain. PET also has been useful in predicting functional recovery and monitoring the effects of various therapeutic approaches. Although functional imaging of the brain with single photon emission computed tomography can successfully be used in the investigation of several disorders of the brain, its role in cerebrovascular disorders is quite limited. PET is a unique modality that studies ischemic diseases of the brain, and it potentially could play a significant role in the management of patients with cerebrovascular disease. This will be further realized when aggressive approaches are used routinely in the future.

Cerebrovascular Disorders↗
PubMed1992

Characterization of radioiodinated TISCH: a high-affinity and selective ligand for mapping CNS D1 dopamine receptor.

In developing CNS D1 dopamine receptor-imaging agents with improved specificity and longer brain retention, an iodinated D1 ligand was synthesized. In vitro and in vivo radiolabeling studies of a new iodinated benzazepine, TISCH [7-chloro-8-hydroxy-1-(3'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3- benzazepine], an analog of SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin e), were investigated. After an intravenous injection, the R(+) isomer of TISCH showed high brain uptake in rats (2.20 and 0.57% dose per whole brain at 2 and 60 min, respectively). The striatum/cerebellum ratio increased progressively with time (12 at 60 min). Ex vivo autoradiography of rat brain sections, after intravenous injection of R(+)-[125I]TISCH, displayed the highest uptake in striatum and substantia nigra, regions known to have a high concentration of D1 receptors, whereas the S(-) isomer displayed no specific uptake. Furthermore, the specific uptake can be blocked by pretreatment with SCH 23390. In vitro binding studies using the rat striatum tissue preparation showed high specific and low nonspecific bindings (KD = 0.21 +/- 0.03 nM). The rank order of potency exhibiting high specificity to the D1 receptor was SCH 23390 greater than (+/-)-TISCH greater than (+)-butaclamol = (+/-)-FISCH [7-chloro-8-hydroxy-1-(4'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine] much greater than WB4101 = spiperone greater than dopamine, serotonin, (+/-)-propranolol, and naloxone. Imaging studies in a monkey with the resolved isomer, R(+)-[123I]TISCH, demonstrated a high uptake in the basal ganglia and prolonged retention. The preliminary data suggest that R(+)-TISCH is selective for the CNS D1 receptor and is potentially useful for in vivo and in vitro pharmacological studies. When labeled with iodine-123, it may be suitable for noninvasive imaging in humans.

Animals↗
PubMed1992

Complications and validity of pulmonary angiography in acute pulmonary embolism.

BACKGROUND: The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED: METHODS AND RESULTS: Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p less than 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%. CONCLUSIONS: The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.

Acute Disease↗
PubMed1992

Changes in normal glycosylation mechanisms in autoimmune rheumatic disease.

To investigate potential mechanisms controlling protein glycosylation we have studied the interrelationship between lymphocytic galactosyltransferase (GTase) activity and serum agalactosylated immunoglobulin G levels (G(0)) in healthy individuals and patients with rheumatoid arthritis and non-autoimmune arthritis. In RA there was reduced GTase activity and increased G(0). A positive linear correlation between B and T cell GTase was found in all individuals. The relationship between GTase and G(0) was found to be positive and linear in the control population and negative and linear in the RA population. Sulphasalazine therapy maintained normal levels of GTase and caused a reduction in G(0) in the RA population. IgG anti-GTase antibodies (abs) were significantly increased in the RA population, whereas IgM anti-GTase abs were significantly decreased in both the RA and the non-autoimmune arthritis groups. These data describe a defect in RA lymphocytic GTase, with associated abnormal G(0) changes, which is corrected by sulphasalazine. A possible regulatory mechanism controlling galactosylation in normal cells is suggested, in which there is parallel control of B and T cell GTase. IgM anti-GTase abs may be integrated into this normal regulatory process. This is disrupted in RA, where the positive feedback between GTase and G(0) is lost and there is an associated increase in IgG anti-GTase abs, which may result from isotype switching as IgM anti-GTase abs are reduced. We suggest that these mechanisms are of relevance to the pathogenesis of RA, and that their manipulation may form part of a novel therapeutic approach.

Adult↗
PubMed1991

Usefulness of noninvasive diagnostic tools for diagnosis of acute pulmonary embolism in patients with a normal chest radiograph.

The value of bedside examination and noninvasive tests in the diagnosis of acute pulmonary embolism (PE) among patients with a normal chest radiograph was investigated. Normal chest radiographs were present in 20 of 260 patients (8%) with acute PE and in 113 of 642 (18%) with suspected acute PE, in whom the diagnosis was excluded. A partial pressure of oxygen in arterial blood less than or equal to 70 mm Hg in a dyspneic patient with a normal chest radiograph was more often seen among patients with PE (9 of 17, 53%) than among patients in whom PE was excluded (18 of 93, 19%; p less than 0.01). However, no combinations of blood gases, signs and symptoms were strictly diagnostic. High probability ventilation/perfusion scans among patients with a normal chest radiograph were indicative of PE in only 6 of 9 patients (67%). Among patients with low-probability ventilation/perfusion scans, 8 of 47 (17%) had PE. This study showed that the combination of dyspnea and hypoxia in a patient with a normal chest radiograph is a useful clue to the diagnosis of PE. Although intuition suggested that ventilation/perfusion scans would yield better results in patients with a normal chest radiograph, the ability to diagnose PE by ventilation/perfusion scans in this subset of patients was not enhanced, except by a reduction of the percentage of patients with intermediate probability scans.

Acute Disease↗
PubMed1991

Neuro-imaging and positron emission tomography of congenital homonymous hemianopsia.

Congenital homonymous hemianopsia is an uncommon asymptomatic visual field defect discovered typically in young adult life that is caused by a diverse group of insults to the retrochiasmal afferent visual system occurring prenatally, at birth, or during early childhood. We treated eight patients with congenital homonymous hemianopsia; seven with damage involving the optic radiations and one with an abnormality of the optic tract. We performed positron emission tomography using 18F-fluoro-2-deoxyglucose on two patients with dense homonymous hemianopsias, lesions of the contralateral optic radiations, and largely intact occipital cortex. These studies showed minimal abnormalities in resting visual cortex glucose metabolism of the affected visual cortex.

Adolescent↗
PubMed1991

Synthesis and characterization of magnetically responsive albumin microspheres containing cis-hydroxyproline for scar inhibition.

Magnetically responsive albumin microspheres containing the proline analog, cis-hydroxyproline, were synthesized and their in-vitro physical properties were characterized. These microspheres have an average size of 1.1 +/- 0.3 microns with 94% of the microspheres less than 2.0 microns. They are uniformly spherical and contain 67% albumin, 22% magnetite, and 8% cis-hydroxyproline. The cis-hydroxyproline is releasable during a 72-h period and demonstrates a slow, releasable pool that constitutes approximately 50% of the incorporated drug. cis-Hydroxyproline is neither chemically nor biologically altered during its incorporation into the microsphere. cis-Hydroxyproline release from microspheres results in the in vitro inhibition of collagen secretion, which is indistinguishable from unincorporated cis-hydroxyproline. In a rat-tail animal model these microspheres were selectively targeted using an external magnetic field applied to a 1.5-2.0-cm target site. Fifty to 80% of the infused microspheres were localized to this site, whereas without a magnetic field only 15-20% of the microspheres are localized to this site. cis-Hydroxyproline microspheres resulted in a 16% decrease in collagen content in a scar model when compared with untreated animals (p less than 0.05). With further refinement of this method of drug delivery, clinically useful inhibition of scar formation may result.

Animals↗
PubMed1991

New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose.

Positron emission tomography (PET) using fluorine-18 (18F)-fluorodeoxyglucose (FDG) has been reported to be a powerful diagnostic and prognostic tool in patients with primary brain tumors. This study was undertaken to compare the prognostic value of: (1) visual grading of [18]FDG uptake in the tumor, (2) the absolute glucose metabolic rate of the tumor (TMRglc), (3) the ratio of glucose metabolism between the tumor and whole brain (T/WB) and (4) between the tumor and contralateral cerebellum (T/CBL). Each of these four parameters was correlated with the survival time in 20 patients with malignant cerebral gliomas. Excellent correlation was obtained with visual grading and reasonably good correlation was obtained with T/WB or T/CBL, but TMRglc alone was only a fair prognostic indicator. Thus, visual grading provides a qualitative analysis and T/WB provides a semi-quantitative analysis neither of which requires arterial blood sampling for quantification of absolute metabolic rates for glucose.

Brain Neoplasms↗
PubMed1991

Positron emission tomography in the investigation of neuropsychiatric disorders: update and comparison with magnetic resonance imaging and computerized tomography.

In many neuropsychiatric disorders, PET imaging offers functional insights unavailable from anatomic imaging alone. Functional deficits may be more extensive than structural findings would indicate, may occur before the detection of anatomic changes, or may even occur in the absence of any structural lesions. We contrast the current role of PET with that of MRI and CT in the investigation of neuropsychiatric disorders including stroke, tumor, head trauma, epilepsy, schizophrenia, movement disorders, normal aging and dementia.

Humans↗
PubMed1991

Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: evolution over the past 2 decades.

Single photon emission computed tomography (SPECT) was introduced in the 1960s to detect breakdowns in the blood-brain barrier and was replaced by x-ray computed tomography in the mid-1970s. The development of the deoxyglucose (DG) technique to measure regional cerebral glucose metabolism by employing either autoradiography, using 14CDG, or positron emission tomography (PET), using 18FDG, added a major dimension to the investigation of brain function. In the late 1970s and early 1980s, the FDG-PET technique was widely used to examine a variety of neuropsychiatric disorders. It soon became apparent that functional imaging was more sensitive than anatomic imaging in detecting abnormalities of the brain related to aging, dementia, tumors, seizures, cerebral vascular accidents, and psychiatric problems. Because of its complexity and the cost involved, PET was used in a limited number of centers in the United States. However, the success of PET resulted in the resurgence of interest in SPECT as an alternative technology after almost a decade. This became possible because of the synthesis of iodine 123- and technetium 99m-labeled radiopharmaceuticals to determine regional cerebral blood flow. Since blood flow and metabolism are coupled in most pathological states, patterns of abnormality noted on SPECT were similar to those seen on PET in many disorders. Since the introduction of high resolution SPECT imaging instruments, the role of SPECT has been further enhanced. The successful synthesis of both positron and single emitting radioligands to image dopamine and other receptors has started a new era in neurosciences and will have a far-reaching impact on the day-to-day practice of neuropsychiatry.

Adult↗
PubMed1991

Lung scanning in the diagnosis of pulmonary embolism: the emperor redressed.

Diagnosis and management of the patient with pulmonary embolism remains a vexing clinical problem. Emboli are often unsuspected clinically. Ventilation-perfusion (VQ) scintigraphy is known to miss some emboli found on pulmonary angiography. Some physicians recommend diagnostic approaches in which the lung scan plays a relatively minor role, and angiography is required for many patients. Major prospective studies recently have made available objective data for formulation and evaluation of diagnostic and therapeutic strategies. These data suggest that the lung scan is a better predictor of patient outcome than has been previously appreciated. The goal of V/Q scanning is not detection of pulmonary emboli per se, but rather the identification of patients at a high or low risk for future embolic events if they are not anticoagulated. Several studies have shown that some emboli found on angiography are clinically benign and, in the absence of persistent thrombosis of the lower extremities, do not require anticoagulation. Treatment trials and clinical follow-up studies have shown that although the V/Q scan is not always predictive of angiogram results, it is a reliable predictor of patient outcome. In the absence of deep vein thrombosis, the low-probability scan identifies a patient population not requiring anticoagulation. When combined with objective studies of the venous system, the ventilation-perfusion lung scan provides a guide to management in the great majority of patients. Pulmonary angiography is required only occasionally.

Angiography↗