Biomedical subjects

J G Walden

Publications and source records attributed to J G Walden.

5 recordsLinked to original sources

PubMed1998

Thioridazine dose-related effects on biomechanical force platform measures of sway in young and old men.

OBJECTIVE: Thioridazine (TDZ) is associated with an increased risk of falls. The purpose of this study was to determine whether (1) thioridazine increases Biomechanics Force Platform (BFP) measures of sway in a dose-related manner, (2) there is a difference in sway between young and old men, (3) there is a correlation between sway and orthostatic changes in BP and HR. DESIGN: Seven younger (aged 20-42) and five older (aged 70-76) healthy male volunteers received, in a randomized order double-blind design, a single oral dose of 0, 25, and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the fourth day of the study. Sway and blood pressure were measured for 24 hours. SETTING: A general clinical research center. MEASUREMENTS: Biomechanics force platform measures of postural sway were measured as the movement of the center of pressure. The elliptical area (EA) and average velocity (AV) were calculated with eyes open and eyes closed. Blood pressure and heart rate were measured for 5 minutes supine and 5 minutes standing. RESULTS: Thioridazine increases BFP sway in a dose-dependent manner. EA increased from 0.56 (SD = .51) cm2 for placebo to 0.88 (SD = 1.09) cm2 for 75 mg TDZ. AV increased from 1.07 (SD = .27) cm/sec, placebo, to 1.43 (SD = .55) cm/sec, 75 mg TDZ. Older men swayed more than younger men. Changes followed the expected time course for TDZ. EA and AV were associated with HR and BP, e.g., SBP versus ln(EA) and ln(AV) (r = -0.21 and r = -0.22, respectively; P < .0001). CONCLUSIONS: Thioridazine increases validated measures of fall risk dose dependently in young and old men. This may explain the effects of neuroleptic drugs on fall risk in older people.

Accidental Falls↗

PubMed1989

Transsynaptic degeneration of motoneurones caudal to spinal cord lesions.

We studied the effects of complete transversal section of the spinal cord, at T8-10, in adult rats, upon the number and morphology of identified motoneurones in lumbar segments L4 and L5. In observations by light and electron microscopy many lumbar motoneurones had structural abnormalities when the interval between surgery and perfusion ranged between a few hours and one week. We found also that as many as 25% of the motoneurones distal to a cord transection disappeared as a consequence of the lesions. We did not find comparable changes in the spinal cord at C6 after transection at T8-10. Complete removal of the cerebellum did not reduce the lumbar motoneurone counts. Bilateral ablation of the "motor" cortex did cause a reduction of motoneurone counts at L4-5; these animals showed normal or near normal spontaneous locomotor activity beginning a few days after the lesion was placed. Motoneurone counts were significantly reduced after partial cord lesions that spared the dorsal funiculi (where the corticospinal tract travels in the rat), but in this case the rats were paraplegic as a result of the lesion. Cord transection at 7 days of postnatal age resulted in reduced motoneurone counts when the rats reached adulthood. Intraspinal or subarachnoid administration of colchicine led to reduced motoneurone counts. Prolonged infusion of a GABA agonist, muscimol, into the lumbar CSF did not prevent the loss of motoneurones produced by cord transection. Pretreatment of animals with a Ca2+ channel blocker (nimodipine) did not prevent the effects of cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Variability and functional recovery in the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism in monkeys.

Fourteen macaque monkeys were injected intravenously with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. All developed the cardinal signs of parkinsonism (akinesia, rigidity, etc.) in varying degrees; some required repeated series of injections of the drug, while others developed the syndrome readily after the first series. Most of the subjects that were kept for longer than 4 weeks after the first dose of the drug showed complete or partial recovery after that time. Measurement, in some of the subjects, of the neostriatal levels of dopamine and dihydroxyphenylacetic acid showed the expected depletion of these substances at the peak of the behavioral action of the drug, but no recovery when the animals had returned to, or near, pre-drug behavioral status. No firm conclusion can be reached at this time as to the reasons for the behavioral recovery or the variability of the effects of the drug across subjects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1981

Anatomical correlates of return of locomotor function after partial spinal cord lesions in cats.

We trained cats to walk on a moving treadmill belt, then subjected them to partial transverse sections of the thoracic spinal cord. Afterwards, we observed their ability to walk on the treadmill, over a period of several weeks, using gait analysis techniques to describe the resultant deficits. The extent of the lesions was verified histologically, and the identity of the spared descending axons from the brain stem was demonstrated by retrograde labeling with horseradish peroxidase. We found that significant sparing or recovery of hindlimb locomotor function is closely linked to sparing of axons in at least one ventrolateral quadrant of the cord. The essential elements probably belong to vestibulospinal and reticulospinal systems.

Animals↗

PubMed1981

Locomotor control in macaque monkeys.

We carried out experiments on young adult macaque monkeys (M.fascicularis) in an attempt to establish whether or not primates possess a locomotor control system consisting of spinal pattern generators modulated by brain-stem locomotor regions. We could not induce 'spinal stepping' in our subjects after spinal cord transection. Sparing of pathways contained in the central sector of the white matter of the cord was sufficient for stepping and walking. 'Controlled locomotion' was elicited in thalamic monkeys by electrical stimulation of the posterior subthalamic region or the midbrain tegmentum just ventral to the inferior colliculi. We conclude that there are significant homologies between this primate species and the cat regarding the probable existence of supraspinal locomotor control structures, but it seems that the presumed spinal step generators in monkeys depend more on supraspinal inputs than they do in cats.

Animals↗