Biomedical subjects
C H Markham
Publications and source records attributed to C H Markham.
Space motion sickness.
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Validating the hypothesis of otolith asymmetry as a cause of space motion sickness.
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VTM--a new method of measuring ocular torsion using image-processing techniques.
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Ventral intermediate thalamotomy for posttraumatic hemiballismus.
An unusual case of hemiballismus following closed head injury is presented. The abnormal movement persisted for 16 years despite medical treatment. Preoperative studies did not reveal a specific lesion within the subthalamic nucleus or within the basal ganglia. A stereotactic ventral intermediate thalamotomy was performed producing a complete resolution of the ballistic movement which persisted for the length of our 12-month follow-up.
Further evidence to support disconjugate eye torsion as a predictor of space motion sickness.
Disconjugate eye torsion in hypo- and hypergravity of parabolic flight was examined in four former astronauts and four previously tested ex-astronauts to replicate an earlier study and to further test the asymmetry hypothesis of otolith function. Results in the new subjects supported the asymmetry hypothesis and confirmed previous findings that those with low scores of torsional disconjugacy on the KC-135 did not suffer space motion sickness in their prior Shuttle missions while those with high scores did. Tilting subjects with high disconjugacy scores slightly to one side and the other failed to find a position that decreased disconjugacy in hypergravity, leading to the conclusion that a simple planar asymmetry about the y-axis was probably not the cause of the observed torsional differences in the two eyes. Disconjugacy increased at 0 G with increasing parabolas, much more so in subjects who had suffered SMS. Because of this, 10 to 20 parabolas were deemed to be a more certain discriminator than a fewer number.
The dystonias.
The various dystonias have been found in at least five different hereditary backgrounds. The gene responsible for one of the dystonias, idiopathic torsion dystonia (ITD), lies on chromosome 9q32-34, with flanking markers now 1-2 cM apart. Magnetic resonance imaging and computerized tomography (CT) abnormalities in the basal ganglia, especially in the putamen, are found in many secondary dystonias. Botulinum toxin therapy is proving very useful in the treatment of focal dystonias.
Otolith function in hypo- and hypergravity: relation to space motion sickness.
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Prediction of space motion sickness susceptibility by disconjugate eye torsion in parabolic flight.
The hypothesis of asymmetric otolith function asserts that physiological or anatomical differences in the two sides of the bilateral gravity-sensing otolith apparatus of the inner ear may be well compensated on Earth, but when exposed to novel gravitational states, the prior compensatory stratagems may be ineffective, leading to unstable vestibular responses and causing the phenomenon of space motion sickness. To investigate this hypothesis, spontaneous eye torsion, a reflex governed by the otolith organs, was examined in the upright position during the hypo- and hypergravity of parabolic flight aboard NASA's KC-135 aircraft in nine former astronauts whose history of space motion sickness was revealed after data analysis had been completed. Results showed that astronauts who had been sick in space had significantly higher scores of disconjugate eye torsion in parabolic flight, and that their responses were consistently different in 1.8 G relative to 0 G compared to astronauts who had not been sick in space. In 1 G, there were no differences in disconjugate eye torsion between the subjects. The results support the asymmetry hypothesis and offer a possible predictive test of space motion sickness.
An examination of male-female differences in progression and mortality of Parkinson's disease.
We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person-years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease.
Longitudinal study of effects of early levodopa treatment on disability and mortality in Parkinson's disease.
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Instability of ocular torsion in zero gravity: possible implications for space motion sickness.
Inherent asymmetries of the gravity-sensitive otolith organs of the inner ear may be well-compensated in ordinary 1 G, but rendered unstable in novel gravitational states. Several aspects of ocular counterrolling and spontaneous eye torsion, reflexes governed by the otoliths, were examined during the hypo- and hypergravity in parabolic flight on the NASA KC-135 aircraft. Among the subjects were two astronauts, one who had suffered space motion sickness during his mission and one who had not. Using an observed separation of scores of torsional instability at 0 G as the criterion, we divided our 10 subjects into the 5 highest and 5 lowest scorers, reminiscent of the approximately 50% who do and the 50% who do not experience space motion sickness (SMS). The astronaut who had had SMS was in the high group; and the one who had not was in the low group. At 1.8 G, the groups defined at 0 G were significantly different in the instability measure. They were also significantly different at both 0 G and 1.8 G in another measure, that of torsional variability. There were no differences between the groups in amplitude of eye torsion in 0 G or 1.8 G. None of the tests were significantly different in 1 G. The results suggest that these tests of eye torsion on the KC-135 might differentiate those who would experience SMS from those who would not. Proof of this speculation awaits replication of the study using only astronaut subjects.
Anatomical evidence of the projection of pontine omnipause neurons to midbrain regions controlling vertical eye movements.
Both anatomical and physiological studies have shown that pause neurons (PNs) in the medial pontine reticular formation project to two groups of burst neurons (BNs) involved in the genesis of horizontal saccadic eye movements: The excitatory burst neurons (EBNs), which lie rostral to the abducens nucleus, and the inhibitory burst neurons (IBNs), which lie caudal to the abducens. This study is concerned with the projection from PNs to a group of vertical BNs in the nucleus of the H field of Forel (H FF) in the caudomedial subthalamus. Three anatomical methods were used to demonstrate this connection. First, intra-axonal horseradish peroxidase (HRP) injection into physiologically identified PN axons demonstrated axonal branching and axonal terminations in and around the H FF. Second, micro-injection of the tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the pontine PN region labelled terminal axons and boutons in the nucleus of the H FF. Third, extracellular pressure injection of HRP into H FF yielded retrogradely labelled pontine PN neurons. These anatomical results confirmed the termination of PNs in areas controlling rapid vertical eye movements as physiologically demonstrated by Nakao et al.: Exp. Brain Res. 70:632-636, '88). This work points to the major role of pontine PNs in the synchronization of BN activity in rapid eye movements in all directions.
Effect of age at onset on progression and mortality in Parkinson's disease.
We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinson's disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.
Anatomy and physiology of otolith-controlled ocular counter-rolling.
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Ocular counter-rolling as a test of otolith function.
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Morphology of physiologically identified second-order vestibular neurons in cat, with intracellularly injected HRP.
The morphology of horizontal canal second-order type I neurons was investigated by intracellular staining with horseradish peroxidase (HRP) and three-dimensional reconstruction of the cell bodies and axons. Axons penetrated in and around the abducens nucleus were identified as originating from type I neurons by their characteristic firing pattern to horizontal rotation and by their monosynaptic response to stimulation of the ipsilateral vestibular nerve. A total of 47 type I neurons were stained. The cell bodies were located in the rostral portion of the medial vestibular nucleus (MVN) and were large or medium sized and had rather elongated shapes and rich dendritic arborizations. The neurons were divided into two groups: those which projected to the contralateral side of the brain stem (type Ic neurons) and those which projected to the ipsilateral side of the brainstem (type Ii neurons). All stem axons of type Ic neurons crossed the midline and bifurcated into rostral and caudal branches in the contralateral medial longitudinal fasciculus (MLF). Two or three collaterals arising close to this bifurcation distributed terminals in a relatively wide area in the contralateral abducens nucleus. Some of these collaterals projected further to the contralateral MVN and thus are vestibular commissural axons. Some of the rostral and caudal stem axons had collaterals which projected to the contralateral nucleus prepositus hypoglossi (PH), nucleus raphe pontis, or medullary reticular formation. There were at least six classes of type Ii neurons, most of which distributed to a relatively limited region in the ipsilateral abducens nucleus and they were categorized according to their future projections into the following categories: A) no further collaterals beyond the abducens nucleus; B) collaterals in the abducens nucleus and a branch descending and terminating in ipsilateral PH; C) projected to the abducens nucleus, PH, and an area rostral to the abducens nucleus; D) projected to the abducens nucleus and to ipsilateral reticular formation rostral and caudal to the abducens nucleus; E) collaterals in the abducens nucleus and a thick caudal stem axon entering and descending in ipsilateral MLF; F) a thick caudal stem axon entering and descending in ipsilateral MLF and no collaterals to the abducens nucleus. Some type Ii neurons also had recurrent collaterals which projected back to the ipsilateral MVN; these may inhibit type II neurons during ipsilateral rotation.
Ocular counterrolling abnormalities in spasmodic torticollis.
Spasmodic torticollis is a focal dystonic movement disorder of unknown origin, long hypothesized to have some vestibular involvement. An examination of otolith function, ocular counterrolling, was performed on eight patients with this disorder. The test consisted of photographing both eyes while the subject underwent rotation in both naso-occipital and earth-horizontal long axes. Measurements of eye torsion were made with a superimposition technique accurate to 0.1 degrees. Results showed all eight patients had abnormal ocular counterrolling. The most notable defect was the lack of sustained eye torsion at the extreme positions, resulting in rolling of the eyes in the direction of head tilt rather than counterrolling, a phenomenon previously observed only in persons with known brain-stem problems. That finding, as well as the majority of the patients showing spontaneous vestibular nystagmus in the dark and directional preponderance with caloric stimulation, implies that one difficulty in spasmodic torticollis lies in central vestibular connections, manifested by disruption of brain-stem pathways.