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Biomedical subjects

C H Markham

Publications and source records attributed to C H Markham.

At least 91 records · Page 5Linked to original sources

A double-blind comparison of levodopa, Madopa, and Sinemet in Parkinson disease.

A sixteen-week study examined the effect of Madopa and Sinemet on patients with Parkinson disease disease suffering nausea or vomiting as side-effects of levodopa therapy and compared the efficacy of the three preparations in controlling the symptoms of Parkinson disease. Following a control period on levodopa, 20 patients underwent four consecutive four-week regimens as follows: (1) double-blind, in which a randomized half received levodopa and half received Madopa; (2) single-blind, in which all received Madopa; (3) double-blind, in which a re-randomized half received Madopa and half Sinemet; and (4) single-blind, in which all received Sinemet. Levodopa administration via Sinemet and Madopa was held to a fixed 20% of prior levodopa dosage. Almost all patients showed great reduction in nausea and vomiting with both Madopa and Sinemet. Seventy percent of the patients showed improvement in disability compared to their levodopa baseline levels. Group means showed no difference between the improvement seen on Madopa and that seen on Sinemet. However, examination of individual responses showed that the majority of patients fared distinctly better on either Sinemet or Madopa.

Adult↗

The relationship of conduction velocity to other physiological properties of the cat's horizontal canal neurons.

The conduction velocity and other physiological characteristics of the first order horizontal canal afferents were studied in 24 anesthesized cats. From their spontaneous discharge patterns, neurons were classified into three groups: regular, intermediate and irregular; The irregular units tended to have a low resting rate, high sensitivity to angular acceleration, frequently exhibited adaptation during prolonged acceleration, and showed a short latency from the time of electric stimulation of the labyrinth to recording the action potential near Scarpa's ganglion. The regular units tended to have a high resting discharge rate, low sensitivity, were mostly non-adapting, and showed longer latency to electric stimulation. The intermediate neurons had a mixed character of regular and irregular units. Based on the very short conduction times (mean 0.34 msec) and the work of Moxon (1971), we conclude the locus of activation of electrical stimulation is neural rather than the receptor cells. Since the latency is due predominantly to conduction in the first order axon, and since there is a direct linear relation between conduction velocity and fiber diameter in the medullated nerve fibers, it is possible to speculate that the regular cells have thin fibers which innervate the slope of the crista, the irregular neurons have thick fibers which innervate the summit of the crista, and the intermediate units have medium caliber fibers which innervate both the slope and summit of the crista ampullaris.

Action Potentials↗

The contribution of the contralateral labyrinth to second order vestibular neuronal activity in the cat.

Vestibular brain stem units of the horizontal canal in the awake C1 transected cat were examined in acute experiments before and after the contralateral vestibular nerve was cut. The latter procedure resulted in an immediate increase in mean resting rate from 19 to 45 spikes/sec and greater spontaneous fluctuations in firing rate. Mean sensitivity to constant accelerations from 2 to 16 degrees/sec2 was significantly reduced. In the 4-6 degrees/sec2 range, for example, mean sensitivity fell from 5.7 +/- 3.2 spike/sec/deg/sec2 (range 0.7-13.6, n = 107) to 2.8 +/- 1.4 (range 0.2-5.5, n = 29). Mean sensitivity to 4-6 degrees/sec2 deceleration was reduced from about 4.5 to 3.0. On the other hand, time constants and the ratio of adapting to non-adapting units was unchanged. Removal of the midline cerebellum, including the vermis and fastigial nuclei in a portion of the animals, did not materially alter the above results. It is concluded that the contralateral labyrinth, acting via the vestibular brain stem commissural pathway, not only exerts a powerful effect on the resting activity of brain stem canal vestibular neurons, but also on their response to acceleration.

Action Potentials↗

Intraaxonal transport of Herpes simplex virus in the rat central nervous system.

Light and electron microscopic observation 3--4 days after microinjection of Herpes simplex virus (HSV) into the left neostriatum of rat demonstrated the following results. (1) Virus labeled nerve cells were found in the ipsilateral substantia nigra; a large number of infected neurons were in the zona compacta and some were in the zona reticulata. No virus infection was evident in the contralateral side. (2) Virus labeled neurons were found in the cortex, a greater number ipsilaterally than contralaterally, and in the dorsal raphé nuclei. Cortical microinjection of HSV led to infection of some cortical cells but no neostriatal cells. We conclude, therefore, that spread of the virus to the cortex, the substantia nigra and the dorsal raphé following neostriatal injection was by retrograde axonal transport. (3) The left neostriatum, where HSV was injected, showed a surprisingly small number of virus infected neurons. The infected neurons were mostly the large neurons; the majority of medium sized neurons were well preserved. There was massive degeneration of nerve terminals throughout the neuropil. Most of these degenerating nerve terminals are considered to be afferent fibers.

Animals↗

Semicircular canal radii of curvature (R) in cat, guinea pig and man.

The radii of curvature (R) of the horizontal (Rh), anterior (Ra) and posterior (Rp) semicircular canals were measured by a new technique (called ROTA) for cat, guinea pig and man. For each canal, data points from the osseous canal were rotated and plotted by computer such that the plane of the sheet of computer plot corresponded to the plane best fitting that canal. The radius of each osseous canal was determined and where necessary, the radius of the arc of data points was corrected for thickness of the absent tissue. For cat, guinea pig and man there are differences in R between canals within a labyrinth suggesting that if other things are equal there could be differences in the average mechanical sensitivity of the canals, which is consistent with physiological recordings from primary vestibular neurons in the cat. The Rs determined by ROTA are compared with Rs determined by conventional histological means.

Action Potentials↗

Semicircular duct and ampulla dimensions in cat, guinea pig and man.

Predictions from the classic theory of semicircular canal operation, the torsion pendulum model, depend upon labyrinthine dimensions and the physical properties of the endolymph. The dimensions of the semicircular canal, duct and ampulla in cat, guinea pig and man were determined from measurements of magnified sections of decalcified temporal bones. Estimates of the effect of shrinkage were obtained from measures in fresh material and it appears shrinkage is probably only a fairly small factor. The dimensions so obtained were used to provide new estimates of the short time constant and other mechanical parameters of the torsion pendulum model in the three species.

Animals↗

Ocular accomodative changes in humans induced by positional changes with respect to gravity.

Ocular accomodation was measured in human subjects while they were rotated at 1 degree/sec about their naso-occipital axes. Sixteen normal subjects were tested with 45 complete and 27 partial revolutions. Naso-occipital rotations ipsilateral to the eye being observed caused accommodative, lens-thickening changes. This effect begin at about 14 degrees from head upright position, tended to reach a maximum by 45 degrees and usually stayed at this level until about 90 degrees. The values tended to return to control level by 180 degrees. With naso-occipital roll in the direction opposite to the eye being observed, there was little change until about 135 degrees at which point further roll was typically clear accomodation. This continued to a maximum at about 270 degrees rotation, and at about 350 degrees returned to control values. Arguments are presented relating this response to the utricles, which are approximately parallel to earth horizontal. The threshold of this response, between 3.7 and 77 cm/sec2, is similar to the threshold of linear acceleration when measured by other means.

Accommodation, Ocular↗

Present morality in parkinson's disease: the ratio of observed to expected deaths with a method to calculate expected deaths.

Excess mortality, i.e. more deaths than expected in a similar normal population, has been reduced in Parkinson's disease by levodopa. A California series and a large collaborative study throughout the United States show the ratio of observed to expected deaths to be normal. In contrast, a New York study was similar patients and a Montreal group of much more severely disabled patients showed greater mortality. The reasons for these differences are unclear, but some variations in results may be attributed to different methods of calculating expected deaths to derive the ratio of observed to expected deaths.

Age Factors↗

Acetylcholine and choline in cerebrospinal fluid of patients with Parkinson's disease and Huntington's chorea.

Lumbar cerebrospinal fluid (CSF) acetylcholine (ACh) and choline (Ch) levels were measured in patients with Huntington's chorea (N=11), Parkinson's disease (N=8), and subjects at risk for Huntington's chorea (N=4), and all three groups were found not to differ significantly from normal controls (N=10). The values found for lumbar CSF ACh and Ch levels in the normal subjects were comparable with previously reported values. The use of physostigmine, a cholinesterase inhibitor, in collecting the CSF samples did not appear to make a difference with regard to ACh and Ch concentrations. Evidence suggesting a ventricular-lumbar gradient, with lumbar CSF Ch concentration being less than ventricular CSF Ch concentration, was found. Finally, ACh levels in CSF did not correlate with corresponding Ch levels.

Acetylcholine↗

Physiologic characteristics of vestibular first-order canal neurons in the cat. I. Response plane determination and resting discharge characteristics.

The response plane and resting rate characteristics of first-order, vestibular, semicircular canal neurons were studied in 67 cats under sodium pentobarbital anesthesia using single-unit recording techniques in the eighth nerve. Five hundred fifty-nine units were classified as to the canal they were associated with by employing an identification technique based on physiologic response patterns to brief, high-level (up to 250 degrees/S2) angular accelerations delivered in various head positions. All horizontal canal neurons had increased firing rates to ampullopetal and all vertical canal units to ampullofugal endolymph flow. The average observed roll and pitch null points for each canal were used to determine the average sensitivity vectors for the right horizontal, anterior, and posterior canals. These sensitivity vectors were at a variance of 4.6-10.2 degrees from those predicted by anatomical measurements (3). The mean resting discharge characteristics of 318 first-order neurons was 36.0 spikes/s (range 0.50-114 spikes/s). No significant difference was noted between horizontal and anterior canal neurons on horizontal and anterior canal neurons on the basis of resting rate. The resting rate of the posterior canal neuron population was significantly lower. The regularity of the resting discharge varied in all three canals and the average coefficient of variation was 0.238 for the population, with a range of 0.298-1.030. The population distribution of all resting-rate statistical parameters appeared to be unimodal, indicating that first-order canal neurons may not be broken into discrete populations on the basis of resting-rate characteristics. Of 47 adequately examined first-order canal neurons, 25 demonstrated a repeatable and predictable alteration in their resting discharge as their position to gravity was reoriented. This alteration was usually nonadapting and varied in magnitude according to the degree of tilt and original starting position. Of 25 canal gravity units, 4 had nearby units from the same canal which were unresponsive to gravity, suggesting the effect was due to a limited distortion of the crista or cupula rather than an overall displacement of the cupula.

Acceleration↗

Physiologic characteristics of vestibular first-order canal neurons in the cat. II. Response to constant angular acceleration.

The physiologic response of first-order vestibular canal neurons, recorded within the internal auditory canal with glass microelectrodes, was studied in anesthetized cats. Neurons from all three canals were subjected to velocity trapezoidal rotations about the canal axis, and about different axes extending up to 90 degrees on either side of the canal axis in "roll" and 30 degrees on either side of "pitch." Each cell examined exhibited a spontaneous discharge and responded to constant angular acceleration in a fashion predictable from the direction of the in-plane acceleration vector and the known receptor hair cell polarization. Under conditions of prolonged constant acceleration, (5 degrees/s2 for 40 s) about 30% of the units which could be classified showed adaptation, 55% did not, and 14%, termed reverse adapting cells, demonstrated a fast rise followed by a slower, continual increase during stimulation. Secondary responses (undershoot or overshoot) were noted in most adapting neurons, but were absent in the reverse adapting group. Adapting neurons were distinguished from the nonadapting group by significantly lower resting rates, more irregular interspike-interval distributions, and greater sensitivity to acceleration. When compared with nonadapting neurons, reverse adapting cells had higher spontaneous rates, less irregular spike intervals, and higher sensitivities. The mean canal sensitivity to angular acceleration for all cells was 2 spikes . s-1/deg . s-2 (range 0.3-7.4 spikes . s-1/deg . s-2). Significant differences in mean sensitivity values between canal neurons were demonstrated, with those from the anterior being the most sensitive, followed by the posterior and horizontal canals, respectively. Time constants for all canals governing the transitory rise (or fall) in rate with constant acceleration averaged 3.8 s. Small differences in mean values were noted between canals but these were not significant. Incremental time constants were found to be slightly but significantly longer (mean = 3.9 s) than decremental time constants (mean = 3.6 s). Some cells showed different tine constants to many trials of one stimulus as well as to different levels of stimulus. Most canal unitary responses were approximately linearly related to stimulus magnitudes over the range of 2-18 degrees/s2. This being the case, the angle between the canal plane and plane of stimulus become the main determinant in the first-order neural response. Here, a linear cosine relationship descriged the three-dimentionsal unitary response curve: maximum canal response was elicited with rotation about the canal axis, while no response was evoked with rotation about an axis approximately 90 degrees to canal axis. Between these two extremes, the response of a cell was determined by the cosine of the angle between the canala axis and the axis of rotation.

Acceleration↗

Does levodopa alter depression and psychopathology in Parkinsonism patients?

Twenty-seven Parkinsonism patients and 31 controls, matched for age and verbal IQ, were tested on an objectively scored personality test (Minnesota Multiphasic Personality Inventory) at the beginning of the patients' levodopa therapy and three months later. Patients, but not the controls, were retested after 15 months of levodopa treatment. The patients, all of whom were intact intellectually, obtained MMPI scores indicating moderate depression before beginning levodopa treatment. There was no test evidence to indicate that levodopa significantly increased or decreased the amount of depression in the patients after three or 15 months of levodopa. The patient group, however, significantly increased their Index of Psychopathology (Ip) score after 15 months of levodopa but not after three months.

Adult↗

Vestibular influences on ocular accommodation in cats.

Electrical stimulation of the utricle in C-1 transected cats (whose labyrinths remained sensitive to natural stimulation) induced bilateral pupillary dilatation and bilateral 0.4 to 3.0 diopter lens change in an anti-accommodative direction. Both effects could still be induced two weeks after cutting the ipsilateral cervical sympathetic trunk. It is concluded that these effects take place by inhibiting the parasympathetic pathway originating in the Edinger-Westphal nucleus. The mediating pathways from the vestibular complex to the Edinger-Westphal nucleus pass through the brain stem in the region outside the medial longitudinal fasciculi.

Accommodation, Ocular↗