In these studies, the effects of recombinant human interleukin 2 (rHuIL-2) were examined on in vitro tumor cytotoxicity by canine blood lymphocytes obtained from peripheral vessels through use of a chromium release microcytotoxicity assay. Cytotoxic activity by lymphokine-activated killer cells was significantly increased, compared with that by untreated lymphocytes in a dose-dependent manner. The maximal effect was attained with 300,000 IU of rHuIL-2/ml. Lymphokine-activated killing also was dependent on the duration of incubation with rHuIL-2. After 1 day of rHuIL-2 incubation, cytotoxicity was significantly increased, compared with that of untreated lymphocytes. Of the 3 times examined, cytotoxicity peaked after 3 days of rHuIL-2 incubation. High levels of cytotoxic activity were still present at 7 days of incubation. Numbers of granular lymphocytes increased over the times examined. These results demonstrate functional and morphologic changes in canine peripheral blood lymphocytes obtained from peripheral vessels after incubation with rHuIL-2 in a dose- and time-dependent manner.

Epidemiologic data were evaluated from all dogs admitted to the University of Minnesota, Veterinary Teaching Hospital (UMVTH) between June 1981 and November 1989. Of 69,890 admissions, 2,077 were Miniature Schnauzers. Uroliths were retrieved from 63 of the 2,077 Miniature Schnauzers admitted. In 20 of the 63 urolith episodes, calcium oxalate was the predominant mineral identified. By comparison, calcium oxalate uroliths were identified in only 56 of the remaining 67,813 non-Miniature Schnauzer canine admissions. The odds that uroliths from Miniature Schnauzers were composed of calcium oxalate was 11.8 times greater than for other canine breeds evaluated at the UMVTH (95% confidence interval = 6.8 to 20.1). Data also were evaluated from files of uroliths retrieved from dogs and submitted to the Minnesota Urolith Center for quantitative mineral analysis between June 1981 and November 1989. Of 3,930 uroliths analyzed, 615 (15.6%) uroliths were obtained from Miniature Schnauzers. Of the 615 uroliths, 175 (28.4%) were calcium oxalate. By comparison, only 550 (16.6%) of the remaining 3,315 from dogs of breeds other than Miniature Schnauzers were calcium oxalate. The odds that uroliths submitted for analysis were composed of calcium oxalate was 2 times greater for Miniature Schnauzers than for dogs of other breeds (95% confidence interval = 1.6 to 2.4). Calcium oxalate uroliths were retrieved more frequently in males than females. The risk for males developing calcium oxalate uroliths was > 3 times the risk for females in both groups of data evaluated. The mean age of all Miniature Schnauzers admitted to the UMVTH with calcium oxalate uroliths was 9 years. Calcium oxalate uroliths were not detected in Miniature Schnauzers younger than 1.7 years.

The area of skin supplied by the afferent fibers in one cutaneous nerve is called the cutaneous area (CA) for that nerve. The CA of peripheral branches of lumbar and sacral spinal nerves responsive to the stimulation of hair follicle mechanoreceptors were mapped in 27 dogs. The amount of overlap among the CA was similar to that found for other CA of the body. The CA of peripheral branches of the sciatic nerve were restricted to the lateral, cranial, and caudal aspects of the pelvic limb distal to the stifle. The CA of the saphenous nerve was located on the medial side of the limb, except for a small area located on the lateral side of the crus. The distal part of the CA of the saphenous nerve was completely overlapped in the hind paw by branches of the superficial peroneal nerve laterally and the medial plantar branch of the tibial nerve medially. The CA for the deep peroneal nerve was located on the dorsal surface of the webbing between digits 2 and 3 and the adjacent skin of these digits. The CA of the plantar branches of the tibial nerve were small in comparison with the diameter of the nerve, suggesting that these branches contained nerve fibers supplying other, deeper structures in the hindpaw and that damage to these nerves would interfere with cutaneous sensation in only a small region on the plantar surface of the hindpaw. Knowledge of the CA of the various branches of the sciatic nerve allows more accurate localization of injury to the sciatic nerve or its branches by using areas of anesthesia.

Failure to obtain passive transfer of immunity via colostrum can be detrimental to the health and survival of a young pup. It has been stated that pups that do not receive colostrum in the first 2 days after birth, be given adult dog serum as a source of protective immunoglobulins. Twenty-five Beagle pups were obtained by cesarean section from 6 Beagle bitches. The pups were allotted to 3 groups at birth. Group 1 was a control group and was allowed to suckle colostrum. Group-2 pups received 22 ml of pooled adult dog serum/kg of body weight (10 ml/lb) SC at birth. Group-3 pups were given 22 ml of pooled adult dog serum/kg by stomach tube at birth. Pups from groups 2 and 3 were separated from the bitch for 48 hours to prevent colostral antibody absorption and were fed a commercially available milk replacer by stomach tube. After 48 hours, all pups were returned to the bitch until they were weaned at 6 weeks of age. Blood samples were collected from all of the pups at birth and on days 1, 2, 7, 14, 21, 28, and 35. The concentration of IgA, IgG, and IgM in serum was determined by radial immunodiffusion and compared by use of a one-way analysis of variance. The control pups had significantly higher serum concentrations of IgA and IgG, than the pups in groups 2 and 3 on days 1 and 2 and 2 and 7, respectively. Group-2 pups had significantly higher serum IgM concentrations on day 1 than either group 1- or group-3 pups.

Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P < 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

The thiamylal sparing effect of midazolam was studied in 30 healthy Beagle and mixed-breed dogs. Using a replicated Latin square design, all dogs were given placebo (saline solution) and 0.025, 0.05, 0.1, and 0.2 mg of midazolam/kg of body weight prior to IV administration of thiamylal sodium. The 0.1 and 0.2 mg/kg dosages significantly decreased the amount of thiamylal required to obtund swallowing reflex and easily achieve endotracheal intubation. Midazolam at 0.1 and 0.2 mg/kg reduced thiamylal requirement by 16.4% and 18.9%, respectively, whereas the 0.05 mg/kg dosage decreased thiamylal requirement by only 6.8%. The 0.2 mg/kg dosage did not further decrease thiamylal requirement beyond that achieved with the 0.1 mg/kg dosage of midazolam. This study demonstrates that the preanesthetic IV administration of midazolam reduces the thiamylal dose necessary to accomplish intubation. The optimal preanesthetic dosage (lowest dosage with significant effect) was 0.1 mg/kg.

Previous work had indicated that the 2 canine hookworms, Ancylostoma caninum and Uncinaria stenocephala, may differ in their susceptibility to treatment with milbemycin oxime. Thus, the study reported here was to examine the effects of this drug on concomitant infections in experimentally infected dogs. Twenty specific-pathogen-free Beagles were inoculated orally with 500 infective-stage larvae from a mixture of larval A caninum and U stenocephala. Quantitative fecal examinations were performed weekly, beginning the day of infection. The dogs were assigned to 2 equal groups, 1 group that received the compound and 1 that received a placebo. The dogs were treated on postinoculation days 30, 60, and 90. For A caninum, egg counts dropped precipitously after the first treatment, and no eggs of this species were found in the feces of any of the treated dogs after the second treatment. The treatments had no significant effect on the mean egg counts made on U stenocephala, although 2 dogs stopped passing eggs entirely after the second treatment. At necropsy, no A caninum were found in any of the treated dogs; the mean number recovered from the control-group dogs was 56.1. Significant difference was not found in the mean number of adult U stenocephala recovered from the treated and control groups (27.0 and 21.7, respectively).

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was > 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,.