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Biomedical subjects

S D Kosanke

Publications and source records attributed to S D Kosanke.

13 recordsLinked to original sources

Effects of rapid pulsed CO2 laser beam on cortical bone in vivo.

Twenty rabbit femurs were used to study the effect of CO2 laser on cortical bone. Sixteen femurs were treated with 20 watts, 3 mm defocused beam, 2 KHZ spike pulse mode CO2 laser for 10 seconds through a circular window in the metaphysis. In four control femurs, the inner cortex was exposed without laser treatment. The animals were killed at 4 and 6 weeks and the specimens studied histologically. All laser-treated specimens showed thermal changes. Three histological zones were observed. A superficial zone of inner cortex close to the beam consisted mainly of carbonization or carbon ash during resorption. An intermediate zone consisted of bone necrosis and healing with associated areas of new bone formation. The deep zone of outer cortex had normal bone with no cellular damage. No such changes were observed in the control specimens. The CO2 laser can be used to generate a controlled zone of tissue ablation, which may make it a potentially useful tool for tumor margin cauterization.

Animals

Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody.

A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.

Animals

Biological evaluation of novel cyclopropyl analogues of stilbene, stilbenediol, and phenanthrene for estrogenic and antiestrogenic activity.

The triphenylethylene-type antiestrogens, such as tamoxifen, are known to be useful in the treatment of estrogen-dependent tumors. However, these compounds display mixed estrogen agonist/antagonist activity which may limit their therapeutic effectiveness. This problem of mixed activity led to the synthesis and identification of a cyclopropyl derivative of cis-stilbene which we have named Analog I. This compound (1,1-dichloro-cis-2,3-diphenylcyclopropane) displayed only antiestrogenic activity in the mouse. The present study was designed to evaluate cyclopropyl derivatives of Analog II for estrogenic and antiestrogenic activity in the rat using the standard 3-d uterotropic assay and the uterine cytoplasmic estrogen receptor assay. Five compounds (B-F) which are cyclopropyl derivatives of stilbene, stilbenediol, and phenanthrene were evaluated in this study. Three of the compounds (B-D) displayed neither estrogenic nor antiestrogenic activity in the rat. The relative estrogenic activities of E and F were 11.3 and 1.5%, respectively, of diethylstilbestrol in the uterotropic assay, and 39 and 6.2%, respectively, of estradiol in the estrogen receptor assay. Neither E nor F was found to display antiestrogenic activity in the rat. The results indicate that the relative estrogenic and receptor binding activities of E and F are similar to those previously observed in the mouse, while B-D appear to be inactive in both species.

Animals

Pneumocystis carinii antigen detection in rat serum and lung lavage.

We developed a modified double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) that detected relatively low concentrations of known Pneumocystis carinii antigen added to buffer or rat sera. Artificial immunization-derived polyclonal rabbit anti-P. carinii antibody was used on the solid phase to capture the antigen. Infection-derived (after P. carinii pneumonia) polyclonal rat anti-P. carinii antibody or a mixture of five murine monoclonal antibodies was used as the antigen detector antibody. Rabbit anti-rat immunoglobulin G antibody or goat anti-mouse immunoglobulin G antibody conjugated to alkaline phosphatase was used as the final antibody. After standardization and optimization of the various reactants in this ELISA system, approximately 53 ng of known P. carinii antigen per ml suspended in phosphate-buffered saline-Tween 20 buffer or 210 ng of antigen per ml suspended in normal rat serum diluted 1:4 could be detected. In addition, an indirect ELISA for P. carinii antibody measurement was developed, using as the antigen a soluble supernatant from a sonicated preparation of Percoll-purified whole cysts and trophozoites to coat the solid phase. Limited studies with sera from a small number of caesarian-obtained, barrier-sustained rats from Charles River Breeding Laboratories, Inc., and the National Institutes of Health and sera from normal and heavily infected rats indicated that the caesarian-obtained, barrier-sustained rats had negligible levels of antibody. The normal and heavily infected rats had variable antibody titers. A significantly high level of P. carinii antigenemia was detected in only 2 (11%) of 18 heavily infected rats. Extensive studies of the P. carinii pneumonia rat model with the ELISA did not reveal significant serum P. carinii antigenemia during the acute stage of infection. However, soluble P. carinii antigen was detected by the ELISA and Western blot assays in the supernatant of lavage fluid after centrifugation to sediment intact organisms. As expected, P. carinii antigens were detected by these assays in the lavage pellet recovered after centrifugation. In conclusion, the antigen assay used in this study detected P. carinii antigen in lung lavage but failed to detect P. carinii antigen in rat serum during the acute phase of infection.

Animals

Staphylococcus aureus-induced shock: a pathophysiologic study.

The purpose of the present study was to determine the effects of lethal intravenous infusions of Staphylococcus aureus (SA) in adult dogs. Animals were maintained under anesthesia for 6 hr and observed until death following the 1-hr infusions of SA organisms. Findings unique to SA administration compared to those with Escherichia coli were the absence of significant necrosis of the mucosal intestinal glands of the small and large intestines; widespread intravascular colonization of bacteria in lung, heart, kidney and adrenal tissues often associated with neutrophil sequestration, microabscess formation, and necrosis; relative constant blood pressure, fibrinogen, fibrin degradation products (FDP), serum glutamic pyruvic transaminase (SGPT), blood (serum) urea nitrogen (BUN), creatinine, pH, and PO2, all of which remained relatively unchanged for 6 hr. Rapid early increases were observed in temperature, respiration rate, lactate, and hematocrit, while PCO2, platelet and white blood cell concentrations decreased. Results suggest unique qualitative differences in responses to Staphylococcal-induced shock compared to those caused by gram-negative bacteria.

Animals

Fatal Beauveria bassiana infection in a captive American alligator.

The entomopathogenic fungus, Beauveria bassiana, was isolated from pulmonary lesions of a dead American alligator (Alligator mississipiensis) at the Oklahoma City Zoo. Colonies of the fungus, which had sporulated in vivo, were found in the thoracic air spaces. Septate, branching hyphae and fungal spores were seen in stained histologic sections of pleura and lung. Dissemination to other viscera had not occurred. This case indicated that B bassiana, a rare vertebrate pathogen, may be a fatal mycotic agent in captive reptiles.

Alligators and Crocodiles

Extracorporeal perfusion without anticoagulation and the response to endotoxin.

The results of this study show that an extracorporeal perfusion system without anticoagulation can be established in the dog under certain conditions. The exact mechanisms merit further investigation. It also points to a model to study the effects of endotoxin without heparin interference and as another model for studying the canine blood coagulation system.

Animals

Long-term intracoronary ethanol administration electrophysiologic and morphologic effects.

The long-term intracoronary infusion of ethanol was used to evaluate the potential of ethanol to produce myocardial injury and cardiac rhythm disturbances. In 22 dogs, electrophysiologic testing was performed 48 hr after cessation of alcohol administration. Multiple premature ventricular beats occurred spontaneously in 3 dogs with spontaneous sustained monomorphic ventricular tachycardia observed in 1 dog. Provocative ventricular pacing produced ventricular tachycardia lasting 20 or more beats in 13 animals with sustained tachycardia observed in 3 animals. Provocative ventricular pacing in the presence of lidocaine or epinephrine produced sustained ventricular tachycardia in an additional 4 dogs. The electrophysiologic properties of Purkinje fibers from the zone receiving ethanol were altered when compared to the control zone. The resting membrane potential was decreased (-76 +/- 2 mV vs. -85 +/- mV, p less than 0.001) with a decrease in action potential amplitude (91 +/- 4 vs. 109 +/- 2 mV, p less than 0.001) and phase 0 upstroke (231 +/- 27 vs. 456 +/- 25 V/sec, p less than 0.02). Prolonged refractoriness was observed in the ethanol zone without a prolongation of action potential duration. Intramural lesions observed within the left circumflex distribution varied from focal acute myofibrillar degeneration and necrosis to severe local scarring. The data suggest that intracoronary ethanol administration at human abuse levels of blood alcohol concentrations produces histologic and electrophysiologic injury in the canine heart. The electrophysiologic ch changes provide a substrate sufficient for the induction and maintenance of ventricular arrhythmia.

Action Potentials