Biomedical subjects

J T Hormes

Publications and source records attributed to J T Hormes.

5 recordsLinked to original sources

PubMed1999

Safety and tolerability study of aptiganel hydrochloride in patients with an acute ischemic stroke.

BACKGROUND AND PURPOSE: Aptiganel (CNS 1102) is a selective, noncompetitive antagonist that acts on the ion channel associated with the N-methyl-D-aspartate (NMDA) receptor and is neuroprotective in experimental focal cerebral ischemia models at a plasma concentration of 10 ng/mL. In human volunteers, dose-limiting effects of aptiganel are blood pressure increases and central nervous system (CNS) excitation or depression. This study assessed the safety and tolerability of non-weight-adjusted doses of aptiganel in patients with acute ischemic stroke. METHODS: This was a double-blind, randomized, placebo-controlled multicenter study in patients presenting within 24 hours of acute ischemic stroke. Ascending single intravenous bolus doses of aptiganel (3, 4.5, 6, and 7.5 mg) were assessed in 21 patients with a 3:1 active drug:placebo randomization schedule. In 15 subsequent patients, selected bolus doses were followed by constant intravenous infusion for 6 to 12 hours (6 mg plus 1 mg/h, n=10; then 4.5 mg plus 0.75 mg/h, n=15) in a 4:1 randomization schedule. Prospectively collected pharmacokinetic data guided selection of infusion rates. Neurological and functional status were recorded at entry and after 1 week, although the study was not designed to test efficacy. RESULTS: Forty-six patients were randomized from 4 centers (3 in the United States and 1 in the United Kingdom): 36 received aptiganel HCl, and 10 were given placebo. Hypertension and CNS events were commonly reported after a bolus dose of 7.5 mg and after a 6-mg bolus followed by an infusion of 1 mg/h. The lower regimen of 4.5-mg bolus followed by infusion of 0.75 mg/h achieved plasma aptiganel concentrations of >10 ng/mL and was well tolerated by patients but still raised systolic blood pressure by approximately 30 mm Hg over baseline. CONCLUSIONS: A 4.5-mg intravenous bolus of aptiganel HCl followed by infusion of 0.75 mg/h for 12 hours is a tolerable dose that can produce plasma drug concentrations shown to be neuroprotective in animal models. However, increases in systolic blood pressure and an excess of CNS effects were both observed at this dose.

Adult↗

PubMed1993

Monitoring of lumbosacral nerve roots during spinal instrumentation.

A technique is described for intraoperative, multimodality electrophysiologic monitoring of the spinal cord and lumbosacral nerve roots (cauda equina). Simultaneous monitoring with the techniques of electromyography, compound muscle action potentials, and somatosensory evoked potentials is found to provide highly useful information to the surgeon during lumbar spine instrumentations. Compound muscle action potential recordings are used to identify nerve roots in the lumbosacral region, especially when visual identification of the nerve is hindered by scarring or distortion of the anatomy. Electromyography continuously monitors nerve roots at risk by revealing neurotonic discharges when the nerve roots are irritated during surgical dissection or placement of the fixation device. The early warning provided by this technique enables the surgeon to avoid irreversible neurologic damage.

Adult↗

PubMed1988

Periodic sharp waves in baclofen-induced encephalopathy.

Acute encephalopathy and an abnormal electroencephalogram with a periodic sharp wave pattern developed in a 58-year-old woman shortly after she received a few doses of baclofen. The clinical and electroencephalographic abnormalities improved promptly after the medication was discontinued.

Baclofen↗

PubMed1988

Toluene abuse causes diffuse central nervous system white matter changes.

We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2-weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill-defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene-induced metabolic changes in myelin.

Brain↗

PubMed1986

Neurologic sequelae of chronic solvent vapor abuse.

Neurologic abnormalities were seen in 13 of 20 patients with a history of chronic solvent vapor (primarily toluene) abuse for 2 or more years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cognitive (60%), pyramidal (50%), cerebellar (45%), and brainstem/cranial nerve (25%) findings. Eight of nine CTs revealed diffuse atrophy of cerebral hemispheres, cerebellum, and brainstem. BAERs were abnormal in three of four patients, and EEG abnormalities were seen in three of seven patients. Chronic exposure to solvent vapor may cause persistent neurologic impairment.

Adolescent↗