Hematologic values and plasma and tissue folate concentrations in dogs given phenytoin on a long-term basis.

During earlier investigations of the hepatic effects in dogs of long-term administration of phenytoin alone or in combination with primidone, erythrocytic macrocytosis, neutropenia, neutrophilic hypersegmentation, and thrombocytopenia were observed. Such abnormalities were observed most often in dogs given phenytoin and resembled those known to be attributable to folate deficiency in human beings with epilepsy treated with phenytoin. To pursue the theory that these hematologic aberrations were caused by drug-induced folate deficiency, 12 dogs were given a diet specifically formulated to contain a minimally adequate concentration of folate. After 2 weeks, phenytoin was administered daily (400 mg, PO, q 8 h) to 8 of the 12 dogs for 54 weeks. A CBC, bone marrow aspiration biopsy, and measurement of plasma and RBC folate concentrations were done every 3 weeks. Bone marrow aspirates were examined by transmission electron microscopy after 24 and 36 weeks, and at the end of the treatment period. Hepatic folate concentration was also determined in all dogs before and after treatment. Excretion of formiminoglutamic acid, as a marker of folate deficiency, was measured in all dogs at the end of the study. All dogs remained healthy throughout the treatment phase. Consistent abnormalities were not observed in the blood or bone marrow of treated dogs. Plasma and RBC folate concentrations decreased in control and treated dogs as a result of dietary restriction (P less than or equal to 0.02), and remained stable until the end of the study. The RBC folate content decreased further in treated dogs (P less than or equal to 0.02), although the hepatic folate content was similar in control and treated dogs. Treated dogs did not excrete formiminoglutamic acid more rapidly than did control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycosylated hemoglobin in dogs: precision, stability, and diagnostic utility.

The precision and stability of the ion exchange chromatography assay for canine glycosylated hemoglobin (HbA(1)) were examined. The coefficient of variation (CV) of within-run replicate assays was 1.3 to 2.6%; the CV of between-run duplicate assays was 3.1%. The mean HbA(1) content in 44 healthy dogs was 7.1% (SD = 1.1%, range = 5.1-9.7%). Paired aliquots of 12 blood samples were stored at 4 degrees C and 25 degrees C, and HbA(1) was measured on the day of collection and at 3, 5, and 7 days after collection. In the blood stored at 4 degrees C, no significant increase in the HbA(1) content was seen. No significant increase in HbA(1) content was found in the blood stored at 25 degrees C after 3 days, but dramatic increases were observed after 5 and 7 days of storage. No significant difference was observed in the HbA1 content in heart blood collected 18 hours after death from 9 dogs kept at 25 degrees C. The HbA(1) content was measured in 10 hospitalized diabetic dogs. Five of the dogs had received no insulin and all 5 had elevated HbA(1) values. The other 5 dogs had received insulin for 1 to 9 months; 2 of the 5 had increased HbA(1) content. The HbA(1) content was determined periodically for 9 months in one diabetic dog and it declined from 14% to 8.2%.

Nasal rhinosporidiosis in the dog.

Rhinosporidiosis was diagnosed in six dogs from the southeastern United States. All six dogs had unilateral nasal polyps with multiple small white sporangia visible beneath the surface. Microscopically, the polyps consisted of organisms and fibrovascular tissue with a surface of columnar or squamous epithelium. Juvenile sporangia were unilamellar, 15-75 microns in diameter, nucleated, and accounted for about 65% of sporangia seen. Approximately 5% of the sporangia were in intermediate stages of maturation, were bilamellar, 100-150 microns in diameter, and contained immature endospores. Mature sporangia comprised about 30% of the total, were usually unilamellar, 100-400 microns in diameter, and contained a mixture of immature and mature endospores. The inner layer of the wall of the intermediate sporangia and the single wall of the mature sporangia were argyrophilic and carminophilic. Ultrastructurally, the earliest stage contained a nucleus and many ribosomes, lipid droplets, and phagolysosomes. Maturing sporangia contained discrete membrane-bound, round clevage products. These structures subsequently matured to spores, each of which had a wall and contained a nucleus and many lipid droplets. The organism from one dog was cultured and grown in vitro for 7 months and is the first successful cultivation of Rhinosporidium seeberi.

Erythrogram and red cell distribution width of Equidae with experimentally induced anemia.

The erythrogram (erythrocyte histogram) and red cell distribution width (RDW) were evaluated in 5 purebred horses and 1 pony of mixed breeding with experimentally induced anemia. Four horses were studied for 6 weeks after 20% of their estimated blood volume was removed on each of 2 consecutive days (40% total blood loss; acute blood-loss group). Two horses were given acetylphenyl hydrazine IV daily, until acute Heinz body hemolytic anemia was induced; the 2 horses were then evaluated for 6 weeks. One horse and the pony had 20% of their estimated blood volume removed via phlebotomy once each week for 8 weeks to induce iron-deficiency anemia (chronic blood-loss group); the horse had been partially depleted of iron before the study began. Weekly blood samples were examined for changes in the erythrogram, RDW, mean cell volume (MCV), and erythrocyte glucose-6-phosphate dehydrogenase activity. Fourteen days after acute blood loss, mild increases were seen in the MCV, which persisted to day 42. The RDW was increased at day 14 and remained increased until day 42; however, the percentage increase was double that of the MCV at days 14, 21, and 28. Erythrograms had mild extensions of the right slope at days 14 to 28. Mean erythrocyte glucose-6-phosphate dehydrogenase activity increased in all 3 groups, but individual concentrations were erratic. In the 2 horses with acute hemolytic anemia, modest increases of similar magnitude were seen in RDW and MCV.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of lithium chloride on renal structure and sodium-potassium-adenosine triphosphatase activity in dogs.

Lithium chloride was given intraperitoneally to dogs at a dosage of 125 mg/kg body weight for three days. Kidneys were removed for morphologic examination and quantitation of sodium-potassium-adenosine triphosphatase (Na-K-ATPase) activities in cortical and medullary tissue. Light microscopy showed no changes in the kidneys, but cytoplasmic vacuolation and dilatation of the cisternae of the endoplasmic reticulum were seen ultrastructurally in the epithelial cells of the distal tubule and cortical and medullary collecting ducts. Mean cortical Na-K-ATPase activity was 1.49 +/- 0.25 and 1.70 +/- 0.31 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. Mean medullary Na-K-ATPase activity was 4.71 +/- 0.41 and 5.01 +/- 0.47 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. It was concluded that lithium produced morphologic changes in the distal nephron, but had no effect on renal Na-K-ATPase activity.

The anemia of chronic renal failure revisited.

The mechanisms of the anemia of chronic renal failure are reviewed. Ineffective erythropoiesis is undoubtedly the major cause of this anemia. The contributions of inadequate erythropoietin secretion by the diseased kidneys, suppressive effects of uremic "toxins" on erythropoiesis and red cell survival, excess blood loss, and plasma concentrations of parathyroid hormone, calcium and phosphate are discussed.

In vivo and in vitro responses of cats sensitized with viable Mycobacterium bovis (BCG).

Cats were injected subcutaneously with viable Mycobacterium bovis (BCG), and immune responses were evaluated at various times after injection. The BCG injection produced fever, leukocytosis, neutrophilia, and lymphadenopathy of regional lymph nodes. Intradermal tuberculin injection produced responses consistent with delayed type hypersensitivity reaction in the treated cats at postinoculation day 21. Skin responses to tuberculin were not significant at postinoculation day 49. The cellular infiltrate at the tuberculin injection site at 48 hours after injection was an admixture of polymorphonuclear cells and mononuclear cells. The BCG produces strong intradermal skin responses in the cat, but the response was not long-lived as in cattle and guinea pigs. The BCG injection did not produce significant changes in the absolute total lymphocyte and absolute T-lymphocyte numbers in peripheral blood. The percentage of T-lymphocytes was significantly higher in the BCG-treated group. Differences were not observed in lymphocyte blastogenesis with tuberculin and non-specific mitogens between BCG-treated and control cats.

Bioevaluation of plasma polymerized films in skeletal muscle.

Plasma polymerized ethylene (PPE), styrene (PPS), and chlorotrifluoroethylene (PPCTFE) were synthesized by exposing the monomeric gases to an inductively coupled radio frequency "glow-discharge" field. The polymer films were deposited on poly(dimethyl) siloxane (medical grade Silastic), which was then surgically implanted in rat paravertebral muscle for periods up to 84 weeks. The biocompatibility of the plasma deposited films and uncoated Silastic was evaluated by qualitative (graded inflammatory cell response) and quantitative (connnective tissue capsule thickness) techniques as a function of time. The morphological features of the connective tissue capsule and the plasma polymerized films were examined by SEM after 75 weeks of implantation. Results showed that the acute inflammatory cell migration around PPS and PPCTFE was at a maximum in 2 weeks, decaying to control levels in 4 to 8 weeks. The PPE response was judged as less than the control response up to 4 weeks. After 8 weeks no qualitative difference could be detected between the plasma polymerized films and Silastic. On the other hand, a quantifiable change in fibrous capsule response as a function of time and material was noted until 24 weeks. From these data we conclude that these types of films do not elicit an untoward foreign body reaction at a skeletal muscle implant site in rats.

Performance of implanted biogalvanic pacemakers.

Seventeen unipolar cardiac pacemakers powered by hybrid biogalvanic cells were implanted in dogs. Long term clinical effects and electrical performance in vivo of the generators were investigated. The biogalvanic cells were designed to provide 50 years of generator operation. No systemic pathological changes which would be attributed to the generator or the biogalvanic cell were observed. Local reaction to implants was mild and not significantly different from the one observed in conventional pacemaker implantations to date. The electrical performance of the biogalvanic cells was very encouraging. Final steady-state cell voltage levels of .65V to .75V were reached in 100--150 days after implantation and remained constant in 3 units to date which represents over 36 months after implantation for each generator.