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Biomedical subjects

L C Pettigrew

Publications and source records attributed to L C Pettigrew.

51 records · Page 3Linked to original sources

Efficacy and mechanism of action of a calcium channel blocker after global cerebral ischemia in rats.

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. We then measured hippocampal ATP, phosphocreatine, and glucose contents immediately and 2 hours after ischemia, and measured learning ability (working and reference errors) on an eight-arm radial maze beginning 30 days after ischemia. To gain insight into the possible mechanism of action, we measured production of arachidonic acid metabolites (eicosanoids: TXB2 and 6-keto-PGF1 alpha) and hemispheric and hippocampal cerebral blood flow by the [14C]butanol indicator fractionation technique immediately and 2 hours after ischemia. Nicardipine was associated with fewer working errors (p less than 0.02) but no difference in reference errors. The drug had no effect on energy metabolites, cerebral blood flow, or eicosanoids immediately after ischemia, but ATP, phosphocreatine, and cerebral blood flow all returned to normal levels significantly more rapidly during reperfusion in treated rats. Nicardipine improves behavioral, electrophysiologic, and mitochondrial function after ischemia without preventing cellular damage and improves postischemic reperfusion. The drug's positive effect appears to occur during reperfusion.

Adenosine Triphosphate↗

Brain extraction of a calcium channel blocker.

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. The corrected first-pass extraction of nicardipine, compared to water, was calculated to be 30.7% into the hemispheres and 42.3% into the hippocampi. The uptake was greater into the ischemic hemispheres (p less than 0.001). These data suggest that dihydropyridines are available to binding sites and calcium channels in neurons.

Animals↗

Movement disorders and AIDS.

We studied seven patients with AIDS or AIDS-related complex (ARC) and movement disorders. Three had hemichorea-ballismus, two had segmental myoclonus, one had postural tremor with dystonia, and one had paroxysmal dystonia. Besides the hyperkinesias, two patients had parkinsonism, and one had cerebral Whipple's disease. In two, the movement disorder preceded other evidence of AIDS; in three others, the diagnosis of AIDS was not considered until there was a movement disorder. The movement disorders were attributed to toxoplasmosis in four patients (one confirmed at autopsy), viral encephalitis, vacuolar myelopathy, and CNS Whipple's disease.

Acquired Immunodeficiency Syndrome↗

Production of eicosanoids by deendothelialized rabbit aorta: interaction between platelets and vascular wall in the synthesis of prostacyclin.

Production of eicosanoids by deendothelialized aorta in response to continuous infusions of arachidonic acid and platelet suspensions was determined in a rabbit aorta perfusion model. 6-keto-PGF1 alpha production was stimulated by AA infusion in a dose-related manner. Infusion of AA at 4 micrograms/ml/min led to an initial production rate of 0.64 +/- 0.29 ng/min which gradually increased to 0.93 +/- 0.11 ng/min at the 20th min of infusion. When the concentration of AA infusion was increased to 10 micrograms/ml/min, 6-keto-PGF1 alpha production increased to 1.14 +/- 0.86 ng/min initially but declined with time. PGE2 production in response to AA 10 micrograms/min/ml was steady at around 5 ng/min while PGF2 alpha and TXB2 production were only slightly above the control. Perfusion of rabbit washed platelet suspensions at a rate of 3 X 10(8) plt/ml/min raised 6KPGF1 alpha production. The production was further increased when platelets were pretreated with 1-benzylimidazole (5 mM), along with a concurrent reduction in TXB2 release. Pretreatment of platelets with aspirin, on the other hand, abolished the increase in 6KPGF1 alpha production. Our data indicated that the vascular smooth muscle cells can efficiently utilize PGH2 produced by platelets to synthesize PGI2.

Animals↗

Hemidystonia: a report of 22 patients and a review of the literature.

Hemidystonia defined as involuntary, sustained posturing of the unilateral arm, leg, and face was studied in 12 male and 10 female patients. Hemidystonia was caused by cerebrovascular disease in eight patients, perinatal trauma or childhood injury in four, head trauma and its sequelae in three, neuronal storage disorders in two, neurodegenerative disease in two, lesions after thalamotomy in two, and presumed encephalitis in one. Sixteen patients (73%) had CT evidence of contralateral basal ganglia damage, history of hemiparesis, or both. Brain damage before 7 years of age produced contralateral hemidystonia with a mean delay of 9-7 years. In older patients hemidystonia appeared within 6 months after injury. Hemidystonia may result from a disconnection between the striatum and the thalamus with relative preservation of the corticospinal pathways.

Adolescent↗

Neurologic complications of a coral snake bite.

A 27-year-old man was bitten by a coral snake in Mexico. Within 24 hours he had ptosis, dysphonia, difficulty chewing, and limb weakness. His symptoms peaked at 72 hours with loss of ambulation. Neurologic examination was consistent with severe myasthenia. Repetitive stimulation of the median nerve showed a postsynaptic defect that was not corrected by edrophonium. He was monitored in an intensive care unit, but received no antivenom globulin or acetylcholinesterase inhibitors. The syndrome abated in 3 weeks.

Adult↗

Diagnosis and treatment of lumbosacral plexopathies in patients with cancer.

Eleven patients were diagnosed as having lumbosacral plexopathy at M. D. Anderson Hospital, Houston, from August 1981 through July 1982. Four causes were documented: plexopathy secondary to metastatic disease (six cases); radiation-induced plexopathy (two cases); plexopathy secondary to intra-arterial chemotherapy (two cases); and plexopathy as the result of a second primary tumor (one case). Patients with plexopathies secondary to tumor or irradiation complained of pain in the ipsilateral lower extremity. Computed tomography of the pelvis was the most accurate method of documenting tumor in the region of the lumbosacral plexus. Radiation therapy records of patients with cervical carcinoma were reviewed with respect to positioning of intracavitary radium, which was thought to be responsible for the development of radiation-induced plexopathies. Radiation therapy and/or systemic chemotherapy provided relief of pain and improvement of neurologic deficits in three patients with metastatic involvement.

Adult↗

Baseline hemodynamic state and response to hemodilution in patients with acute cerebral ischemia.

Hemodynamic data were obtained in 9 patients (mean age 65 yrs) with carotid territory cerebral infarct within the preceding 24 hours (mean 14 +/- 8) as part of a pilot study testing the feasibility and safety of hypervolemic hemodilution. Pulmonary arterial catheters (PACs) were placed without complication in all patients, and after baseline measurements were obtained, up to 1500 cc of 6% hetastarch in 0.9% sodium chloride was administered the first day and up to 1000 cc per day the second and third days. Pulmonary wedge pressure (PWP) rose from 6.3 +/- 3.5 to 14.4 +/- 3.4 mm Hg (p less than 0.001) without development of congestive heart failure in any patient. This was accompanied by a drop in hematocrit (Hct) from 40.3 +/- 3.4 to 32.9 +/- 2.0 (p less than 0.001) and rise in cardiac output (CO) from 4.3 +/- 1.0 to 5.3 +/- 0.6 (p less than 0.05). Phlebotomy of 250 cc was performed in 2 patients and 500 cc in one in order to reduce Hct to desired levels. The volume of fluid needed to raise PWP to 15 was unpredictable (2361 +/- 1106 cc) and therefore PACs were necessary to monitor the rate and volume of fluid administration. The data show that PWP is sufficiently low and Hct sufficiently high following stroke in most patients that hemodilution by volume expansion with phlebotomy added if necessary can be undertaken safely with appropriate monitoring of hemodynamic function, and that this therapy results in optimal reduction of Hct and increased CO without risk of hypotension.

Acute Disease↗

Cerebral infarction: assessment of patterns using ultra-fast MR contrast imaging.

We describe a rapid MR imaging technique, applying functional analysis to images obtained during the tissue transit of injected contrast material into the cerebral circulation, which has potential for assessment of the altered hemodynamics in cerebral ischemia. This technique utilized turbo-FLASH imaging maximizing the T1 relaxivity properties of gadopentetate dimeglumine with positive contrast enhancement.

Cerebral Infarction↗

Cerebral hemodynamics and cerebral blood volume: MR assessment using gadolinium contrast agents and T1-weighted Turbo-FLASH imaging.

PURPOSE: To assess the degree and regional pattern of first-pass brain enhancement using dynamic MR imaging. MATERIALS AND METHODS: Ultrafast MR imaging (1.06-second acquisition time per image) was performed in 19 healthy subjects following a bolus IV injection of a gadolinium contrast agent; 36 patients with suspected pathology were studied using the same protocol. RESULTS: Calculated percent blood volumes were 4.9% for right cortical gray matter, 4.8% for left cortical gray matter, and 2.6% for white matter. Subtraction images were obtained that depicted the first pass "blood pool" pattern of enhancement (gray and white matter) which was significant. CONCLUSION: Preliminary evidence suggests utility for cerebral "blood pool" imaging, especially if reduced image acquisition times can be achieved.

Adult↗