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Biomedical subjects

D G Robertson

Publications and source records attributed to D G Robertson.

At least 55 records · Page 3Linked to original sources

Electrophysiologic changes following treatment with organophosphorus-induced delayed neuropathy-producing agents in the adult hen.

Although clinical, pathological, and biochemical effects of organophosphorus-induced delayed neuropathy (OPIDN) have been intensively investigated in the adult hen, detailed electrophysiological studies are lacking. Adult white leghorn hens were treated with a single oral dose of either 30 mg/kg tri-2-cresyl phosphate (TOCP), 750 mg/kg TOCP, 4 mg/kg di-n-butyl-2,2-dichlorovinyl phosphate (DBCV), or 30 mg/kg di-n-butyl-2,2-dichlorovinyl phosphinate (DBCV-P). The 750 mg/kg TOCP and DBCV, but not the 30 mg/kg TOCP and DBCV-P, treatments resulted in clinical signs of OPIDN and mild to marked damage of the tibial nerve 21 days after dose. Twenty-four hr lymphocyte neurotoxic esterase (NTE) inhibition was used as an index of brain NTE inhibition for the various organophosphorus compound (OP) treatment. Twenty-four hr lymphocyte NTE inhibition for 30 mg/kg TOCP, 750 mg/kg TOCP, DBCV, and DBCV-P was 54.1, 87.1, 84.8, and 68.3%, respectively. Twenty-one days after dose, the TOCP-treated hens exhibited some abnormalities in conduction velocity and action potential duration in the tibial or sciatic nerves. No abnormalities were observed in action potential parameters of either the DBCV or DBCV-P treatments. Neurotoxic OP (TOCP and DBCV) treatment resulted in decreased refractoriness in the tibial nerve, increased refractoriness in the sciatic nerve, and elevated strength duration threshold for both nerves. These changes were not present in nerves from DBCV-P (a non-neurotoxic NTE inhibitor)-treated hens. These results suggest that refractory period and strength duration abnormalities in peripheral nerve correlate well with the production of OPIDN and are evident without coincident clinical signs or histopathology.

Action Potentials↗

The pathogenesis of trimethyltin chloride-induced nephrotoxicity.

In exploratory studies aimed at elucidating CNS effects due to heavy metal toxicity, signs of compromised renal function were seen in rats. The studies reported here describe the sequential steps of the development of nephrotoxicity by trimethyltin chloride (TMT) in rats. Single doses of 12.25 mg/kg TMT administered orally to 150- to 175-g Long-Evans rats elicited overt signs of toxicity including behavioral abnormalities and marked weight loss. Concurrent with the development of these signs, nephrotoxicity was manifested as functional kidney compromise and associated histopathologic evidence of tubular damage. Pathological changes in the kidneys from treated rats were hyaline droplet inclusions, attenuated brush border, basolateral vacuolization, and eosinophilic granular casts in the proximal tubule cells. These lesions were detected as early as 2 days post-treatment and progressed with time in an orderly and sequential fashion. Renal lesions between 5 and 8 days were mild to severe cortical tubular dilatation, hydropic degeneration, and diffuse hyaline droplet deposition in the lower nephron tubules. Medullary edema and exfoliation of degenerated tubular epithelial cells with cast formation followed from 8 to 11 days. The morphological changes were accompanied by marked elevation of blood urea nitrogen, parallel with polyuria at Day 2 and oliguria by Day 14. Behavioral abnormalities as well as weight loss correlated well with the time course and severity of renal dysfunction and progression of morphological changes. A second experiment compared the effects of TMT in rats of different weights. Heavier rats were more sensitive than lighter rats to the nephrotoxic effects of TMT. These effects were independent of recognizable neurotoxic effects of TMT in the hippocampus.

Animals↗

Quantitative assessment of trimethyltin induced pathology of the hippocampus.

The pathology induced by trimethyltin in the hippocampus was investigated using a detailed morphometric model. Male Long-Evans rats were dosed with 3 mg/kg trimethyltin chloride (TMT) for three consecutive days and sacrificed at subsequent interim period. Total brain volume was not significantly affected; hippocampus volume decreased within 4 days after completion of dose. Pyramidal cells were more sensitive to the toxic effects of TMT than granule cells, in addition, dorsal pyramidal cells appeared to be more sensitive than ventral pyramidal cells. The dorsal CA4 region appeared to be the most susceptible to cell loss, although the dorsal CA1 region also exhibited significant reductions. The most dramatic reduction in cell numbers occurred between 14 and 28 days post-dose. Cell loss within the CA3c and CA4 but not the CA1 region was preceded by decreased nuclear volume. In addition cellular loss within the dorsal CA1 region appeared to be most pronounced within a well defined rectangular patch of cells immediately adjacent to the CA3-CA1 junction. The data further suggest that TMT is a potent toxicant to the hippocampus. This toxicity is delayed, and selectively affects well defined groups of cells within the structure. Additionally, differences in nuclear pathology suggest that more than one mechanism may be involved in the destruction of these target cell populations.

Animals↗

Kinetics of standing broad and vertical jumping.

The purpose of this study was to determine the contributions made by the leg muscle groups to the external mechanical work done in standing broad and vertical jumping. Six subjects were filmed jumping from a force platform. Linked-segment analysis and inverse dynamics methods were used to compute the muscle moments of force and power and work output created by these moments of force. Results support the principle that all three extensor moments of force summate in both types of jumping but that the sequence of contractions was not from proximal muscles to distal as is stated by the continuity principle. Instead all three extensor moments act simultaneously to produce leg extension. The contributions made by the three muscle groups were not the same for the two types of jumps. For the propulsive phase of the standing broad jump the contributions of the hip, knee, and ankle muscles were 45.9%, 3.9%, and 50.2%, respectively, whereas, for the vertical jump the contributions were 40.0%, 24.2%, and 35.8%, respectively. These results indicate that broad jumping utilizes the muscle groups differently than vertical jumping and show the importance of the hip and ankle musculature in the production of external work in jumping.

Biomechanical Phenomena↗

Decreased tetanic contracture of rat skeletal muscle induced by pyridostigmine.

The purpose of this study was to compare the effects of various regimens of pyridostigmine administration on the contractile strength of skeletal muscle. Rats were exposed to pyridostigmine according to 3 dosing schedules: 2 mg/kg ip daily, 5 mg/kg X d by sc infusion, and 25 mg/kg X d by sc infusion. After 1, 4, 10, and 20 d of exposure, measurements were made of muscle tension during tetanic stimulation, and of muscle mass, erythrocyte acetylcholinesterase activity, and body weight. Pyridostigmine produced a dose-dependent decrement in the contracture generated during tetanic stimulation. Peak effect was observed after 4 d of exposure but remained depressed after 20 d. The magnitude of the decrement correlated with the frequency of the tetanic stimulation (from 20 to 100 Hz). Muscle tension at the end of the tetanic stimulus was affected to a greater extent than the initial tension. The 25-mg/kg infusion of pyridostigmine significantly depressed erythrocyte acetylcholinesterase activity throughout the study and also decreased body weight on d 1-4. No change in muscle mass was observed in any treatment group. These results show that pyridostigmine exposure results in decrements in skeletal muscle contracture that are dose-dependent, frequency-dependent, and time-dependent. The effect is probably not the result of muscle wasting and does not correlate well with erythrocyte acetylcholinesterase inhibition. The results are consistent with effects of pyridostigmine, both presynaptically and postsynaptically, at the neuromuscular junction that affect neurotransmitter release and receptor responsiveness.

Acetylcholinesterase↗

Electrophysiologic characteristics of tibial and sciatic nerves in the hen.

The peripheral nerve of the hen has become an increasingly important animal model in studies of peripheral neuropathy, especially that induced by organophosphorus agent exposure. However, few electrophysiologic studies have been performed, and few data on normal peripheral nerve function exist. The purpose in the present study was to measure the characteristics of the compound action potential of peripheral nerves of the healthy hen. The results showed that conduction velocities of the tibial and the sciatic nerves were 41 m/s and 60 m/s, respectively. The relative refractory period was slightly shorter in the sciatic nerve. The tibial nerve exhibited a lower threshold for stimulation and a significantly shorter chronaxie (19 microseconds) than did the sciatic nerve (25 microseconds). Variability between animals was relatively small. These data should provide useful reference points on studies in which peripheral neuropathy is induced or suspected.

Action Potentials↗

Mechanical energy in sculling and in rowing an ergometer.

The purpose of this study was to quantify and contrast the instantaneous segmental and total body energy patterns of rowing a single scull racing shell with rowing a Gjessing (Norway) rowing ergometer (RE), and to contrast energy savings through exchanges of mechanical energy among segments and conversions of energy within segments. Four scullers, two male and two female, were filmed at three stroke rates while rowing on a stationary and a wheeled RE, and rowing in single sculls racing shells. Coordinates of joint markers were digitized, digitally filtered, and combined with estimated body segment parameters using link-segment mechanics to obtain segmental centre of gravity kinematics. Mechanical energy and internal work analyses were conducted to compute the energy savings due to exchange and interconversion of segmental energy. The internal work was least in the wheeled RE and greatest in the boat. Savings of energy through exchanges were greatest in the boat, and least in the stationary RE. Savings of energy through interconversion were greatest in the wheeled RE. The interconversions (expressed as a percentage of total work) were quite similar for both the boat and the stationary RE. The additional energy savings with the wheeled RE allow the conclusion that wheeled RE testing will permit athletes to work at stroke rates similar to racing levels.

Adult↗

Difference between end-tidal and arterial PCO2 in exercise.

The relation between end-tidal carbon dioxide tension (PETCO2) measured by infrared analysis and arterial carbon dioxide tension (PaCO2) during exercise was systematically examined in five healthy adults at two power outputs (25 and 50% VO2max) and at three frequencies of breathing (15, 30, and 45 breaths/min). PETCO2-PaCO2 varied between -2.5 and +9.1 Torr, was inversely related to the frequency of breathing (r = 0.475), and directly related to tidal volume (VT; r = 0.791) and CO2 output (r = 0.627). An equation was obtained by multiple regression analysis, to predict PaCO2 from PETCO2: PaCO2 = 5.5 +0.90 PETCO2 -0.0021 VT (r = 0.915). The equation was applied to measurements of PETCO2 obtained in two previous studies in 10 subjects in which PaCO2 had been measured, and was found to predict PaCO2 to within 1.04 Torr (+/- SD) for PaCO2 between 25 and 58 Torr (n = 56; r = 0.962). The effect of the response characteristics of the CO2 analyzer on the measurement of PETCO2 was also systematically examined by comparison with a fast-responding respiratory mass spectrometer.

Adult↗

Symposium on allergic lung disease. II. The late asthmatic responses.

Immediate asthmatic responses have been regarded as the characteristic type of asthmatic response to follow exposure to inhaled allergens in patients with extrinsic asthma. They begin within minutes, clear within one to three hours and are inhibited by disodium cromoglycate but not by corticosteroids. They involve the reaction of antigen with antibodies usually of the IgE class. In recent years allergen inhalation tests have demonstrated the frequent occurrence of late asthmatic responses, either following immediate responses (dual responses) or occurring in isolation. The late asthmatic responses begin two to six hours after the allergen challenge, are prolonged and often severe, and are inhibited by both disodium cromoglycate and corticosteroids. The mechanisms involved in their provocation are not clearly understood but from the allergic viewpoint they may involve the participation of IgG +/- IgM antibodies and/or IgE antibodies. Late asthmatic responses explain the frequent occurrence of allergen-induced prolonged asthma. Their features suggest that they are more important than immediate responses in the pathophysiology of asthma.

Airway Resistance↗