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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↗
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↗
PubMed1976

Slow sodium inactivation in Myxicola axons. Evidence for a second inactive state.

Sodium inactivation and reactivation have been examined in voltage-clamped Myxicola axons after long-lasting membrane depolarizations produced either directly by changes in holding potential or indirectly by elevation of external K+ concentration. The results suggest the existence of a second inactivated state of the sodium channel with associated voltage-dependent rate constants at least two orders of magnitude lower than those of the fast inactivation process commonly examined. No specific influence of external [K+] on slow Na+ inactivation could be detected.

Animals↗
PubMed1976

Activation-inactivation coupling in Myxicola giant axons injected with tetraethylammonium.

Myxicola giant axons internally injected with tetraethylammonium chloride to block potassium currents were examined under voltage clamp. The sodium inactivation time constants obtained from the decline in INa during step depolarizations were substantially smaller than those obtained using conditioning prepulses to the same potentials and the ratios agreed with previous observations using TTX. Inactivation shifts were also measured and found to be comparable to previous results.

Animals↗
PubMed1976

Sensitivity of the sodium and potassium channels of Myxicola giant axons to changes in external pH.

Myxicola giant axons were studied using standard voltage-clamp techniques in solutions whose pH values ranged from 3.9 to 10.2. Buffer concentrations of 50 mM or greater were necessary to demonstrate the full effect of pH. In acidic solutions the axon underwent a variable depolarization, and both the sodium and potassium conductances were reversibly depressed with approximate pKa's of 4.8 and 4.4, respectively. The voltage dependence of GNa was only slightly altered by acidic conditions, whereas there occurred large shifts in GK along the voltage axis consistent with a substantial decrease in net negative surface charge in the vicinity of the K+ channels. The sodium and potassium activation rate constants were decreased by acidic conditions, but the results could not be described as a simple translation along the voltage axis.

Animals↗
PubMed1976

Potassium current kinetics in Myxicola axons. Effects of conditioning prepulses.

In Myxicola giant axons the time constants for activation of the potassium conductance (GK) after prepulses less depolarized than a test pulse are comparable to the time constants for turn off of GK after prepulses more depolarized than the same test pulse. The absolute magnitude of the steady-state level of GK is also independent of prepulse amplitude in Myxicola. The results are contrasted with recent observations on voltage-clamped frog nodes.

Animals↗
PubMed1976

Experimental studies of the effects of extrinsic factors on conduction in normal and demyelinated nerve. 1. Temperature.

Previous studies in experimentally demyelinated mammalian nerves have demonstrated that a reversible conduction block occurs with small increases of temperature within the animal's normal body temperature range. This phenomenon is believed to be the mechanism for clinical temperature effects in multiple sclerosis. This study examines some quantitative thermal relationships in demyelinated nerves of guinea pigs with experimental allergic neuritis. The observed results in normal and experimental animals are in good agreement with previous theoretical calculations based on the effects of temperature on the voltage and time-dependent behavior of the ionic permeabilities of the nodes of Ranvier. Guinea pigs with increasing motor dysfunction generally exhibited corresponding increases in the overall latency of the conducted action potential, as well as decreases in amplitude. In addition, the lower the initial velocity increment per degree of temperature elevation, the lower was the temperature at which conduction block began to occur. Except for a few cases in which the recorded action potential was bimodal, with response at both normal and prolonged latency, the results tended to indicate a remarkedly uniform involvement of the sciatic nerve within the region of temperature control.

Action Potentials↗
PubMed1976

Neuroelectric blocking factors in human and animal sera evaluated using the isolated frog spinal cord.

The effects of sera from guinea-pigs with experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS) patients were evaluated and compared with the activity of control sera using the isolated frog spinal cord. Ventral root responses (VRR) were recorded during supramaximal ipsilateral dorsal root stimulation in the presence and absence of 25% serum. In control experiments with normal human and guinea-pig sera we observed a consistent, reversible increase in VRR averaging 20% and 17% respectively, and in no case was any significant decrease produced. In contrast, sera from EAE guinea-pigs 12 to 19 days after injection produced an equally rapid, reversible decrease in VRR. The decrease averaged 36% and was highly significant (P less than 0.0001) relative to controls. Similarly, sera from MS patients on the average decreased the VRR by 26%, and this again was significant compared with controls (P less than 10(-6).

Animals↗
PubMed1976

Movement phosphenes in optic neuritis: a new clinical sign.

Positive visual phenomena (phosphenes) elicited by eye movements have been described in normal individuals and in myopes with vitreous opacities. In the present paper we describe eye movement-induced phosphenes that appear to be related to optic nerve involvement in patients with optic neuritis and multiple sclerosis. This phenomenon is not associated with vitreous or retinal defects, nor is it similar to phosphenes observed in normal individuals. Instead, it shares many characteristics with the well-known Lhermitte sign and is believed to represent a similar phenomenon.

Adult↗