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Biomedical subjects

F A Davis

Publications and source records attributed to F A Davis.

At least 19 recordsLinked to original sources
PubMed1992

Action potential refractory period in axonal demyelination: a computer simulation.

Axonal demyelination leads to an increase in the refractory period for propagation of the action potential. Computer simulations were used to investigate the mechanism by which changes in the passive properties of the internodal membrane increase the refractory period. The properties of the voltage dependent ion channels can be altered to restore conduction in demyelinated nerve fibers. The ability of these alterations to decrease the refractory period of demyelinated model nerve fibers was compared. The model nerve fiber contained six nodes. The action potential was stimulated at node one and propagated to node six. The internode between nodes three and four was demyelinated in a graded manner. The absolute refractory period for propagation of the action potential through the demyelinated internode increased as the number of myelin wraps was reduced to less than 25% of the normal value. The increase in refractory period was found to be due to a reduction in the rate or repolarization of the action potential at node three. The delay in repolarization reduced the rate of recovery of inactivated Na channels and slowed the closing of K channels. The rate of repolarization of node three was reduced by the conduction delay for the depolarization of node four caused by demyelination of the preceding internode. In these simulations the increase in refractory period due to demyelination was eliminated by slowing the onset of Na channel inactivation. A small reduction of the K conductance also decreased the refractory period. However, larger reductions eliminated this effect.

Action Potentials↗
PubMed1991

4-Aminopyridine in multiple sclerosis: prolonged administration.

In an earlier study, we demonstrated efficacy of single oral doses of 4-aminopyridine (4-AP) in improving motor and visual signs in multiple sclerosis (MS) patients for a mean of 4.97 hours. We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double-blind study. Nine of these patients were also tested with identically appearing placebo. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. Seventy percent of the daily 4-AP improvements lasted 7 to 10 hours. The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours (83% of the average 8.53-hour treatment-observation period) compared with 2.36 hours for placebo (26% of the average 9.06-hour treatment-observation period). No serious side effects occurred. 4-AP is a promising drug for the symptomatic treatment of MS.

4-Aminopyridine↗
PubMed1990

Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis.

4-Aminopyridine (4-AP), a potassium channel blocker, restores conduction in blocked, demyelinated animal nerve. Its administration to multiple sclerosis (MS) patients produces transient neurological improvements. Vision improves after either oral or intravenous administration, whereas motor function improvement has been reported only with the latter. To assess further its potential as a practical symptomatic treatment, we studied the efficacy of single, oral doses of 4-AP on both visual and motor signs in MS. Twenty temperature-sensitive male MS patients were given either 10 to 25 mg of 4-AP or identically appearing lactose placebo capsules. Static quantitative perimetry, critical flicker-fusion, visual acuity, visual evoked potentials, and videotaped neurological examinations were monitored. All of 15 MS patients given 4-AP mildly to markedly improved. Motor functions (power, coordination, gait) improved in 9 of 13 involved, vision in 11 of 13, and oculomotor functions in 1 of 2. Improvements developed gradually at doses as low as 10 mg, usually beginning within 60 minutes after drug administration, and reversed gradually over 4 to 7 hours. No serious adverse effects occurred. No significant changes were observed in 5 MS patients given placebo. We conclude that orally administered 4-AP produces clinically important improvements in multiple, chronic deficits in MS. Further studies are warranted to assess efficacy and safety of prolonged administration.

4-Aminopyridine↗
PubMed1987

Selective blockade of components of potassium activation in Myxicola axons.

The K+ conductance in Myxicola giant axons activates in two phases which are pharmacologically separable. The fast phase of K+ activation is specifically inhibited by 4-aminopyridine and by the substitution of D2O for H2O. We suggest Myxicola giant axons, like the amphibian node of Ranvier, may possess more than one variety of K+ channel.

4-Aminopyridine↗
PubMed1987

4-Aminopyridine improves clinical signs in multiple sclerosis.

Twelve temperature-sensitive male patients with multiple sclerosis and 5 normal men were monitored before, during, and after the intravenous injection of 7 to 35 mg of 4-aminopyridine (4-AP) in 1- to 5-mg doses, every 10 to 60 minutes. Static quantitative perimetry, flicker-fusion frequency, visual acuity, and videotaped neurological examinations were performed. Ten of the 12 patients showed mild to marked improvement. Vision improved in 7 patients, oculomotor function in 5, and motor function (power, coordination, gait) in 5. Improvements developed gradually within minutes of drug injection at doses as low as 2 mg, and gradually reversed around 2 to 4 hours after the peak drug effect. No effects were observed in 5 patients given saline injections. No serious side effects occurred in either the normal subjects or the patients receiving 4-AP. It is concluded that 4-AP lessens multiple neurological deficits in multiple sclerosis and, furthermore, that the K+ channel is functional in demyelinated central nervous system axons in humans. The improvements with 4-AP are substantial enough to be of transient therapeutic benefit in selected patients.

4-Aminopyridine↗
PubMed1985

Acute improvement in exacerbating multiple sclerosis produced by intravenous administration of mannitol.

The mode of action of adrenocorticotropic hormone (ACTH) treatment in exacerbating multiple sclerosis was studied by short-term infusions of agents that mimic specific and limited pharmacological actions of ACTH and observing for temporally phase-locked clinical changes. The study was double blinded, and agents were administered while the patients were being treated with a standard course of 10-day intramuscular ACTH therapy (40 U twice daily). Antiedema, alkalotic-hypocalcemic, extraadrenal, and sodium-retaining actions were studied using infusions of mannitol, sodium bicarbonate, ACTH, and sodium chloride, respectively. Seven of 8 patients receiving placebo infusions (2.5% glucose) showed no significant clinical change and 1 exhibited an equivocal improvement. Five of 9 patients receiving mannitol showed definite signs of clinical improvement phase-locked to drug administration, with subsequent gradual reversal to baseline. Similar improvements occurred with infusions of NaHCO3 in 5 of 8 patients and of ACTH in 4 of 8 patients. Three of 7 patients given NaCl infusion showed possible mild improvements. The results indicate that mannitol and NaHCO3 induced transient acute improvement in signs at the 95% confidence level in patients with exacerbating multiple sclerosis, with ACTH having a similar effect at the 90% confidence level. These agents mimic some of the known effects of ACTH, which may be important in the therapeutic action of ACTH in multiple sclerosis. A possible role for mannitol and high-dose ACTH in the treatment of demyelinating disease warrants further study.

Adrenocorticotropic Hormone↗
PubMed1978

Discussion groups for medical patients. A vehicle for improved coping.

Describing 14 professionally run discussion groups for multiple sclerosis patients, this paper delineates appropriate functions and goals of the medical discussion group. Such groups address coping activities related to affiliation with a social reference group, information seeking and, in a more limited way, consolidation of intrapsychic resources. The discussion describes the dynamic issues which arise in the groups and explores ways in which group dynamics interact with the medical format.

Humans↗
PubMed1978

Complement-dependent serum: neuroelectric blocking activity in multiple sclerosis.

In attempting to discover a relationship between the neurologic and immunologic abnormalities in multiple sclerosis, we found a serum factor that inhibits the ventral root response in isolated, perfused frog spinal cords. This effect is correlated with disease activity. Blocking activity of the serum was lost by heating to 56 degrees C, restored by adding complement, and was found in the serum IgG fraction. There was no correlation of neuroelectric blocking activity with measles complement-fixing antibody. An antibody other than that to measles virus may thus have a role in the pathogenesis of multiple sclerosis.

Animals↗
PubMed1978

The effect of haloperidol on the ionic currents in the voltage-clamped node of Ranvier.

Haloperidol (Haldol) selectively inhibits sodium currents at the voltage-clamped node of Ranvier at concentrations ranging from 0.013 to 13 muM. The action potential is reduced or abolished while the membrane potential is not significantly changed. The dose-response curve is described by a Langmuir adsorption isotherm with an apparent dissociation constant of 6 X 10(-7) M. Sodium current time-to-peak and the permeability-voltage relationship are not affected, although at higher concentrations the inactivation time constant is slightly increased. Potassium currents are not altered except at 13 muM where there is an occasional nonsystematic effect. Leakage currents are not changed at any concentration.

Action Potentials↗
PubMed1977

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.

Acne Vulgaris↗
PubMed1977

Lymphocyte subpopulations in multiple scerlosis: comparison with neuroelectric blocking activity.

Lymphocyte subpopulations were determined in patients with confirmed multiple sclerosis using a new technique in which immunoglobulin bearing (lg+) cells are rosetted directly with purified anti-light chain antibody-coated human erythrocytes, while T cells are first sensitized with specific anti-human thymus antisera prepared in b4b4 rabbits, and then indirectly rosetted with purified anti-rabbit light chain allotype antibody-coated human erythrocytes. In 45 percent of the patients, there was a striking decrease in the percentage of T lymphocytes and a reciprocal elevation of lg+ and N cells. In another 20 percent, T cell depression was not accompanied by Ig+ elevation. The remaining 35 percent had normal lymphocyte profiles as did all patients with nondemyelinating neurologic diseases. However, we found no significant correlation between the lymphocyte profiles and prospective clinical evaluation of these patients and no correlation between alterations in lymphocyte profile and the presence of neuroelectric blocking factors in the peripheral blood of multiple sclerosis patients.

Amyotrophic Lateral Sclerosis↗