Publications by authors named "Grotta J"

Calcium channel blockers such as nicardipine improve outcome after global cerebral ischemia and may attenuate ischemic neuronal injury by preventing calcium influx and binding to calmodulin. We followed the temporal and regional sequence of neuronal calcium-calmodulin binding in normal rats (n = 6), untreated ischemic rats (n = 15), and ischemic rats treated with 0.05 mg/kg/hr s.

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We evaluated several doses of cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS-19755), a potent competitive N-methyl-D-aspartate (NMDA) receptor antagonist, systemically administered either before or after 20 to 30 minutes of global ischemia in rats. We measured outcome by mortality, histological damage by light microscopy, and learning ability on an eight-arm maze, and determined the drug's mechanism of action by an immunohistochemical assay of calcium-calmodulin binding. High-dose treatment begun prior to ischemia resulted in reduced cellular damage in severely ischemic hippocampal tissue, but also caused high mortality due to respiratory depression.

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Presynaptic release of glutamate into the extracellular compartment and activation of receptor-operated calcium channels may contribute to ischemic neuronal damage. We evaluated the effect of baclofen, a selective inhibitor of presynaptic glutamate release, on mortality, working memory, and light microscopic hippocampal and cortical damage in the four-vessel occlusion model of cerebral ischemia using 64 male Wistar rats. Baclofen (10 mg/kg i.

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Since ionic Ca2+ binds with intracellular calmodulin (CaM) before activating proteases, kinases, and phospholipases, demonstration of persistent Ca2+-CaM binding in neurons destined to show ischemic cellular injury would support the concept that elevated intracellular Ca2+ plays a causative role in ischemic neuronal damage. In order to characterize Ca2+-CaM binding, we used a sheep anti-CaM antibody (CaM-Ab) which recognizes CaM that is not bound to Ca2+ or brain target proteins. Therefore, immunohistochemical staining of brain sections by labeled CaM-Ab represented only unbound CaM.

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We followed 19 men and 19 women with asymptomatic carotid stenosis up to 30 months to determine whether hematologic or lipid abnormalities could identify those individuals developing progressing carotid atherosclerosis (defined as an increase in mean percent stenosis greater than or equal to 19% or an increase in a single region of greater than or equal to 23%) on B-mode carotid ultrasonography performed at 2- to 6-month intervals. Our patients demonstrated increased beta-thromboglobulin, platelet factor 4, and fibrinogen compared with age-matched controls. Eight patients developed progression of carotid stenosis, and this group had higher baseline low-density lipoprotein (LDL) and fibrinogen than the 30 nonprogressing patients.

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A prospective study of 100 consecutive admissions to a university neurology inpatient service was done to assess the prevalence and spectrum of autoimmune rheumatic disorders, most specifically Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and lupus anticoagulant (LA)-associated disorders. All patients underwent a physical exam (PE), a rheumatic disease questionnaire, and serologic testing (ANA, RF, and LA). The 100 patients consisted of 36 men and 64 women, aged 17 to 98 (mean 60) years and included 47 white, 45 black and eight other.

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A variety of eyelid movement abnormalities have been attributed to lesions of the central nervous system. Apraxia of lid movements, and especially of lid opening, has received the least attention. We present 2 cases of lid opening apraxia and propose that this abnormality may be due to right hemisphere dysfunction.

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Reperfusion of ischemic brain is associated with production of thromboxane A2 (TXA2), a proaggregatory vasoconstrictor. We used an animal model of transient forebrain ischemia to study the effects of 1-benzylimidazole (1-BI), a selective inhibitor of thromboxane synthase, upon cerebral eicosanoid levels and cerebral blood flow. Male Wistar rats were subjected to 30 minutes of four-vessel occlusion.

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The selective vulnerability of pyramidal neurons in the CA1 hippocampal region in ischemic rat brain may be preceded by regional alterations of energy metabolism during early reperfusion. We measured ATP, phosphocreatine (PCr), and glucose in paramedian and lateral CA1 and in an area showing little postischemic cell loss, CA2. ATP levels in paramedian CA1 were depressed immediately after 30 min of ischemia (P less than or equal to 0.

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In the United States alone, there are 1.7 million stroke survivors at any given time, 75% between the age of 55 and 84 years, thereby posing a formidable rehabilitation task. In order to reduce short-term mortality from strokes, management should focus on improved pre-stroke status of high-risk patients and on improved recognition and therapy of medical complications of stroke during the first 3 weeks.

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Dihydropyridine calcium channel blockers such as nicardipine are under evaluation for treating acute cerebral ischemia because they may increase cerebral blood flow by causing vasodilation and because they may be cytoprotective in part by limiting production of arachidonic acid metabolites. We demonstrated in a previous study that nicardipine improves postischemic neuronal function, as measured by somatosensory evoked potentials, without reducing the extent of light-microscopic CA-1 hippocampal histologic damage. To characterize further the effect of nicardipine on global ischemic injury, we administered the drug beginning 24 hours before 30 minutes of four-vessel ischemia in Wistar rats.

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A 59-year-old man presented with jugular foramen syndrome caused by a mass with roentgenographic and histologic features highly suggestive of a glomus jugulare tumor. However, electron microscopic examination of the surgical specimen revealed features diagnostic of a previously unsuspected renal cell carcinoma. Because primary tumors of the glomus jugulare and metastatic renal cell carcinoma may present with the same clinical and roentgenographic findings and look similar histologically, careful electron microscopic examination of the tumor and urologic screening should be performed in suspected cases of glomus jugulare tumors.

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A standardized neurologic assessment scoring instrument was developed and tested for use in a multicenter trial of hypervolemic hemodilution in acute hemispheric stroke. Components of the neurologic examination pertinent to hemispheric stroke syndromes were emphasized. The scale was evaluated using 16 acute stroke patients for concurrent validity (Pearson coefficient r = 0.

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Dihydropyridine calcium channel blockers may be effective treatment for acute cerebral ischemia, but the uptake of these drugs into the brain is unknown. A 0.2-ml bolus of [14C]nicardipine hydrochloride and [3H]water was injected into the common carotid arteries of 7 normal and 7 ischemic rats.

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Cerebral blood flow correlates poorly with outcome after stroke, and most therapies aimed at increasing cerebral perfusion have not succeeded in predictably reducing neurological deficit. Newer approaches such as hemodilution and thrombolysis may prove to be more effective but might be most advantageous if combined with efforts to correct postischemic disturbances in cellular metabolism.

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