Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary leaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable disiroxicam (Feldene) is a nonsteroidal anti-inflammatory P drug primarily used to treat arthritis in humans.' It has also been reported to have antitumor activity in chemically inducal2-' and transplanted* tumors in rodents and in metastatic tumors in people.' We previously reported a phase I clinical trial of piroxicam in 62 dogs with naturally occurring tumors and identified dose-related gastrointestinal toxicity and subclinical renal toxicity.'o Antitumor activity was observed in this phase 1 trial in dogs with transitional cell carcinoma (TCC) of the urinary bladder." To hrther investigate the antitumor activity of piroxicam, we conducted a phase I1 clinical trial in 25 dogs with TCC of the bladder. The study reported here includes 9 dogs from the phase I trial and 25 dogs from the phase I1 trial. Although the purpose of a phase I trial is to evaluate drug doses and toxicity, useful information on tumor response and survival was available in the dogs with TCC in the phase I trial we conducted." Therefore, these dogs were included in this report. Materials and Methods Clinical Trial DesignEntry requirements for this study included the presence of measurable (by cystography), histopathologically confirmed TCC of the urinary bladder, performance status consistent with expected minimum survival of6 weeks, and informed consent by the owner. Dogs that had previously received chemotherapy had evidence of tumor progression on that therapy, and a minimum of 3 weeks was required between the last chemotherapy and entry into this trial.Dogs were evaluated at the Purdue University Veterinary Teaching Hospital on days 0, 28, and 56. These evaluations included physical examination, complete blood count, serum biochemistry profile, urinalysis, thoracic radiography, and cystography (pneumocystography or double contrast cystography). Care was taken to perform the cystography in the same manner (same radiographic technique, same amount of contrast material) for each evaluation of a patient. Piroxicam was administered orally at a dose of 0.3 mg/kg sid. This dose was established based on a previous phase I clinical trial." When secondary bacteria...
To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen M S were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic M S was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic M S had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic M S and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic M S were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB those of diabetic lipemic M S resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low There is evidence that primary hyperlipoproteinemias occur in dogs, but these disorders have not been well characterized, and their etiologies have not been established."6 In one report, primary hyperlipoproteinemia was believed to be the cause of the persistent fasting lipemia of five Miniature Schnauzers. Serum from these dogs formed cream layers on refrigeration, indicating the presence of chylomicrons. Triglyceride concentrations were moderately to markedly increased, and cholesterol concentrations were moderately increased. Lipoprotein electrophoresis showed lipoproteins that stayed at the origin (expected behavior of chylomicrons), and greater amounts of beta and alpha-2 migrating lipoproteins than were seen in healthy dogs.5Several hereditary disorders that cause fasting hypertriglyceridemia occur in people, and many of these are characterized by chylomicronemia. The hyperlipoproteinemias that involve chylomicronemia are often associated with abdominal pain and/or pancreatitis, and dia- 253
Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastrointestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.
Summary Endotoxin (LPS) was quantitated in experimental subjects and in horses with naturally occurring gastrointestinal strangulation obstruction and/or septicaemic diseases to establish the fate of LPS and the clinical usefulness of the Limulus amoebocyte lysate (LAL) assay. The assay was validated for sensitivity (10 pg/ml), recovery (90 to 106 per cent), intra‐assay precision (CV = 5.5 per cent) inter‐assay precision (CV = 11 per cent), and stability of diluted, heat treated, frozen samples (at least 90 days). Plasma concentrations of LPS after sublethal (3 μg/kg) jugular or portal vein bolus injections of LPS rose to 4000 pg/ml and 1500 pg/ml respectively followed by a rapid phase of clearance. Peak plasma concentrations of LPS, associated with slow portal infusion, were lower than peak values associated with bolus injections, remained elevated during the infusion (2 h), but rapidly decreased after infusion was stopped. Thirty seven horses with 38 episodes of naturally occurring gastrointestinal or septicaemic disease were assayed for LPS. Eight episodes involving gastrointestinal disease and eight involving septicaemic disease were positive for LPS. It is concluded that the LAL assay is sensitive and reliable for detecting LPS in equine plasma and it may have clinical value for establishing the severity of endotoxaemia or for distinguishing between septic and non‐septic conditions. Problems of rapid clearance of LPS from plasma, low concentrations, the possibility of sample contamination, and the time and method of sample procurement remain to be addressed.
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