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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 307 records · Page 17Linked to original sources

Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

The expense, length of time and number of animals required for routine toxicity testing have provided the incentive for finding alternative techniques which are faster, less expensive and equally valid. The purpose of this work was to examine the value of a simple in vitro test (hemolysis) as a correlate of the neurotoxicity produced by commonly used industrial organic solvents. Incubation of rat erythrocytes with organic alcohols produced hemolysis which correlates with the potency of the same alcohols to suppress membrane excitability, measured as reduction in the evoked action potential of the rat sciatic nerve. The hemolytic activity also reflects changes in water solubility among the compounds and thus can be used as an index of in vivo neurotoxicity, the extent of which partly depends on absorption of the agent and delivery to nerve tissue. Hemolysis therefore may be of value as a preliminary test for assessing the neurotoxicity of organic solvents.

Alcohols↗

Urinary chloride concentration in acute renal failure.

The present prospective study was undertaken to evaluate the usefulness of urinary chloride concentration in determining the cause of an abrupt decline in renal function. 99 patients from diverse clinical settings with multiple causes of acute renal failure were evaluated. Urinary chloride concentrations of less than 20 mEq/l were observed in most cases of reversible prerenal azotemia (20 of 21 cases) and were observed in more frequently than urinary sodium concentration of less than 20 mEq/l (13 of 21 cases, p less than 0.01). Only prerenal azotemia accompanying diuretic use was associated with high urinary chloride concentrations (57 +/- 7 mEq/l). When prerenal azotemia occurred in the setting of metabolic alkalosis with bicarbonaturia, urinary chloride was low (4.0 +/- 1.0 mEq/l) while urinary sodium was high (65.0 +/- 19.0 mEq/l). In patients with oliguric and nonoliguric acute tubular necrosis, and in patients with acute exacerbations of chronic renal failure, mean urinary chloride concentration ranged from 40 to 67 mEq/l and mean fractional excretions of chloride ranged from 7.2 to 8.4%. Only 11% of patients with oliguric and nonoliguric acute tubular necrosis had urinary chloride concentrations of less than 20 mEq/l. Urinary chloride concentrations exhibited greater sensitivity and equivalent specificity as urinary sodium concentrations in differentiating patients with reversible prerenal azotemia from those with oliguric and nonoliguric acute tubular necrosis.

Acidosis↗

Color vision in albino subjects.

Color vision testing was performed on a group of ten black tyrosinase-positive albino patients and a group of normal subjects. Testing was accomplished by means of a Farnsworth-Munsell (F-M) 100-hue test and Nagel anomaloscope. As a group, the albino patients showed an increase in number of errors scored on the FM-100 hue test, without any specific axis in the majority of cases. Results on the Nagel anomaloscope showed a 'widening' into the red end of the Rayleigh equation. A possible explanation for this apparent widening is discussed, which emphasizes anticipated results of matching ranges obtained on extrafoveal cones.

Adolescent↗

Usher's syndrome. Ophthalmic and neuro-otologic findings suggesting genetic heterogeneity.

The conditions of 70 patients with Usher's syndrome were studied by ophthalmic and neuro-otologic examinations. Two distinct clinical and presumed genetic types were discernible on the basis of differences in hearing impairment, vestibular sensitivity, and, to a lesser extent, deterioration in retinal photoreceptor function. Distinguishing these two types has relevance for both diagnosis and genetic counseling of patients with Usher's syndrome.

Adolescent↗

Electrophysiologic changes associated with chronic administration of organophosphates.

Changes in the electrophysiologic activity of the rat sciatic nerve were examined after repeated dosing with either of two organophosphate insecticides, parathion, and trichlorfon. Although the parathion treated animals showed overt signs of systemic toxicity, there were no significant changes in any of the measured parameters of sciatic nerve excitability. Trichlorfon, on the other hand, produced dose-dependent changes in the duration, rise time, relative area, and refractory period of the sciatic nerve compound action potential. The observed changes indicated an increased excitability of the nerve. During the early development of these electrophysiologic changes there were no accompanying histologic changes in the nerve. This suggests that changes in nerve excitability may be a sensitive indicator of neurotoxicity, and that continued trichlorfon exposure may lead to a cumulative alteration in nerve function.

Action Potentials↗

Relative refractory period as a measure of peripheral nerve neurotoxicity.

A method is presented for converting the relative refractory period to a linear form which can be used for quantifying changes in peripheral nerve conduction and membrane excitability. Since the relative refractory period is very consistent in nerves taken from animals of a given age, strain, and size, small alterations due to exposure by neurotoxic agents can readily be detected. In the present study rat sciatic nerves exposed to phenol developed a peripheral neuropathy which was detected by an increased relative refractory period. Diisopropylfluorophosphate (DFP), another neuropathic agent, produced a shift in the relative refractory period which was also consistent with the time course of its known neurotoxicity. On the other hand, acrylamide did not change the relative refractory period although the rats exhibited deficits when measured behaviorally (roto-rod and inclined screen tests). This observation is consistent with the view that the acrylamide toxicity initially affects nerve endings and spares the nerve axon. Erythrosin B, an agent which enhances nerve excitability, produced a shift in the relative refractory period which indicated that the nerve was less refractory. These examples point to the value of the relative refractory period as an index of the extent and type of neurotoxicity induced by agents which affect peripheral nerve axons, and suggest that this method may be useful in determining the mechanism of action of neurotoxic agents.

Acrylamide↗

Effect of hypoxia and hypercapnic acidosis on renal autoregulation in the dog: role of renal nerves.

Previous studies suggest that hypoxia and hypercapnic acidosis exert a renal nerve mediated adverse effect on renal haemodynamic function. We therefore examined the effect of hypoxia and hypercapnic acidosis on renal blood flow and glomerular filtration rate responses to lowering renal perfusion pressure from 125 to 75 mmHg in the anaesthetized dog. To study the role of renal nerves in these responses, paired innervated and denervated kidneys were studied in each animal. Hypoxia (PO2 43 +/- 3 mmHg) affected neither renal blood flow nor glomerular filtration rate responses to decreasing renal perfusion pressure. Hypercapnic acidosis (PCO2 71 +/- 2 mmHg; pH 7.03 +/- 0.01) significantly decreased both renal blood flow and glomerular filtration rate as renal perfusion pressure was lowered. This effect of hypercapnic acidosis could be abolished by renal denervation. These findings suggest that hypercapnic acidosis results in renal nerve stimulation, which prevents the usual decrease in renal afferent arteriolar tone that occurs in response to lowering of renal perfusion pressure.

Acidosis, Respiratory↗

Two additional benefits of dark glasses on rod vision in patients with congenital achromatopsia.

The visual performance of nine rod monochromats was measured with photopic stimuli viewed through filters that attenuated the ambient illuminance. In kinetic perimetry experiments, eight of nine patients showed substantially larger visual field size under the experimental as compared to the control conditions. In increment threshold or brightness-matching experiments, long wavelength sensitivity was shown to be enhanced under the experimental conditions.

Adolescent↗

Human platelet phenol sulfotransferase: partial purification and detection of two forms of the enzyme.

To begin to study the usefulness of platelet phenol sulfotransferase (PST) as a possible measure of the enzyme activity in other organs such as the brain, we purified human platelet PST 36-120-fold. Activity toward 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine, 5-hydroxytryptamine (5-HT), and phenol eluted in the same Sephadex G-100 and Affi-Gel Blue column fractions. Specific activities of the enzyme with MHPG, dopamine, 5-HT, and phenol as substrates were 1198, 1068, 401, and 408 units/mg protein, respectively. Optimal assay conditions were established for each substrate. Apparent Km values were 598 microM, 21 microM, 19 microM, and 500 microM for MHPG, dopamine, phenol, and 5-HT, respectively. Apparent Km values for 3'-phosphoadenosine-5'-phosphosulfate (PAPS) with the same four substrates ranged from 0.11 to 0.25 microM. The pH optima were 6.3 for phenol, 6.8 for dopamine, and 7.0 for MHPG and 5-HT. An additional pH optimum at 8.6 was present for 5-HT. A thermolabile form of the enzyme measured with dopamine and 5-HT, as well as a thermostable form measured with phenol, were present. Dichloronitrophenol (10(-5) M) noncompetitively inhibited the thermostable enzyme activity by 96% but decreased the thermolabile activity by only 36%. These studies provide the basis for a more accurate comparison of human platelet PST with the enzyme in the human brain and in other tissues.

Arylsulfotransferase↗