Diagnostic exercise: tumors in a baboon.
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Biomedical subjects
Publications and source records attributed to F A Voelker.
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A sequential 37-step pathway scheme has been devised that describes the actions and events responsible for the onset, development, and decay of carrageenan pleurisy. It is postulated that the subpleural cytotoxicity of absorbed carrageenan initiates the response by producing a biphasic subpleural inflammation, the first phase of which precedes any sign of pleural exudation. Pleural exudation began 1 h after the injection of carrageenan and consisted of mobilized neutrophils and a barely detectable exudate volume. The time course of intrapleural neutrophil mobilization was monophasic (S shaped). Monocyte mobilization began after neutrophil mobilization and was also monophasic. Pleural exudate formation was biphasic. The first exudative phase was sensitive to inhibitors of neutrophil mobilization and arachidonate acid cyclooxygenase (AACO). Drug studies revealed that although neutrophils were required to initiate the first exudative process, the cells of the pleura produced a postulated reactive prostaglandin intermediate that increased vascular permeability and resulted in exudate formation. The etiology of the second exudative phase is unknown. This phase is insensitive to AACO inhibitors but is highly sensitive to steroids. Inhibition of monocyte mobilization by colchicine revealed that these were not associated with any exudate formation. Monocytes are postulated to stop the exudative process. These cells phagocytose the mobilized neutrophils and return the pleural cavity to normal. Thus, in this model of acute inflammation, monocytic function is related solely to anti-inflammatory activities.
Colchicine produced three effects which modified the acute inflammatory response to carrageenan in the rat pleural cavity: (i) inhibition of neutrophil mobilization and concomitant exudate formation (3 hr); (ii) inhibition of monocyte mobilization (21 hr); and (iii) augmented exudate formation (3 and 21 hr). The 1st effect was related to the intraperitoneal dose of colchicine and occurred only at leukopenic dose levels This effect could not be produced by intrapleural injection of nonleukopenic doses of colchicine. The second effect, on the other hand, was produced by intraperitoneal leukopenic doses and to a lesser extent by intrapleural administration of nonleukopenic doses of colchicine. Importantly, the normal biphasic exudative response to carrageenan developed fully in the absence of monocytes. The third effect, a dose-dependent augmentation of both exudative phases of carrageenan pleurisy, was produced by low, nonleukopenic, intrapleural doses of colchicine. The augmented exudate was sensitive to prostaglandin synthetase inhibitors but not to anti-inflammatory steroids. Neither neutrophils nor monocytes were responsible for the augmented exudate. Colchicine, injected into the rat hindlimb or pleural and peritoneal cavities did not elicit the mobilization of neutrophils or a pleural effusion. In addition, colchicine did not affect the magnitude, temporal development, or decay of the potent edematogenic action of serotonin in the rat hindlimb. Thus irritancy was not responsible for any of the effects of colchicine.
The laboratory rat is the most commonly used species in safety evaluation of pharmaceutical compounds. However, surface preparations of the organ of Corti (OC) are difficult to perform in this species largely due to problems in removing the thick, bony otic capsule. A modified technique was developed using rapid decalcification to solve this problem. In addition, scanning electron microscopy was used to quantitate hair cell damage and/or loss after exposure of the OC by microdissection. It was found that hair cell loss and amage could be easily detected and quantified in rats given gentamicin sulfate.
Myxosporidiosis of the skeletal muscle was diagnosed in a pearl scale butterfly fish (Chaetodon). On the basis of light and electron microscopy, the infectious agent was thought to be a Kudoa. The muscle had fusiform cysts containing myxosporidian organisms within hypertrophied fibers. Ultrastructural features of the kudoa organisms were four external shell valves joined by sutural planes. Internally, four pyriform polar capsules with polar filaments were anterior to the sporoplasm.
A baboon (Papio anubis) was used as a model for the study of the physiology of the esophagus. This model closely resembles the human being phylogenetically and physiologically. Base-line lower esophageal sphincter pressure and peristaltic amplitude are similar to that of man. In addition, the anatomic transition from striated to smooth muscle is identical to that of the human esophagus. The sphincter-depressing effect of ketamine anesthesia was demonstrated.
Five cases of amebiasis were diagnosed in goldfish (Carassius auratus) from home aquariums and from a laboratory aquarium. Granulomas containing amoebae were in many organs but were most numerous in kidneys. Because there were pseudopods, food vacuoles, vesicular nucleoli and other ultrastructural characteristics of the organisms, we identified the organisms as amoebae. On the basis of mitotic stages it is possible they belong in the family Hartmannellidae.
The histopathology and serum levels of mice inoculated intravenously with Pseudomonas aeruginosa exotoxin were studied. The toxin exerted a marked effect on the liver but elicited no demonstrable microscopic changes in other organs. The microscopic lesions caused in the liver by a single injection of two 50% lethal doses (LD50) of toxin (2.3 mug) were characterized by necrosis, cellular swelling, and fatty change within 4--8 hr and near total hepatocellular necrosis at 48 hr. Hepatic necrosis was accompanied by a parallel rise in serum levels of aspartate and alanine aminotransferases and alkaline phosphatase. A single injection of 10 LD50 elicited similar but somewhat more rapid degeneration. No progressive lesions were seen after injection of toxoid or of 0.5 LD50 of toxin.
Glossitis, known clinically as "redtongue," was studied in tissues from 34 military working dogs (MWD) in the Republic of Vietnam. This condition was manifested grossly by loss of lingual papillae on the dorsal margins of the rostral third of the tongue. Microscopically, the principal lesions consisted of loss of filiform papillae, hemorrhage and edema in the lamina propria, acanthosis, and cellular infiltration. The cause of glossitis remains unknown at this time.
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