Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in dogs

OBJECTIVE: To determine whether induction of pancreatic necrosis and islet proliferation by d,l-ethionine has potential for treating dogs with beta-cell insufficiency. DESIGN: Eighteen mixed breed dogs of both sexes were given d,l-ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at 2, 14 and 28 d after the last dose. METHODS: Clinical signs during administration and recovery were assessed. Routine biochemical analyses were performed before each ethionine dose and then once weekly. Faecal samples were examined weekly for malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and APTT) were determined on four dogs after ethionine administration. Intravenous glucose tolerance tests were conducted before the first and after the last ethionine dose and then fortnightly. All dogs were necropsied and pancreas, liver, kidney and jejunum were examined microscopically. RESULTS: During ethionine administration all animals displayed vomiting, inappetence, diarrhoea (often with blood), weight loss and depression. Three dogs were euthanased prematurely due to severe illness, but those allowed to recover were eating and brighter 7 d after cessation of ethionine administration. Serum concentrations of TLI, amylase and lipase increased initially, then decreased, during administration but retumed to normal during recovery. Concentrations of ALT, ALP, unconjugated and conjugated bilirubin increased during administration then decreased slowly. Histological examination revealed hepatic lipidosis and necrosis, but no renal or jejunal lesions. In most dogs, faecal examination demonstrated increased undigested starch and muscle, as well as increased digested and undigested fat, during ethionine administration or early during the recovery period, suggesting transient malassimilation. APTT was unchanged but OSPT was prolonged in all dogs. There was no impairment of insulin secretion or glucose intolerance and C-peptide concentrations were unaffected. Immediately after ethionine administration there was delayed insulin degradation and by day 43 there was evidence of increased insulin sensitivity. CONCLUSION: d,l-ethionine administration in dogs appeared not to interfere with insulin secretion, but caused clinical signs and laboratory changes indicative of pancreatic exocrine necrosis, severe hepatobiliary disease and transient malassimilation. Pancreatic and hepatic dysfunction was severe but clinical recovery occurred after ethionine administration ceased. The severe side-effects observed with d,l-ethionine should preclude its potential use for treating diabetes mellitus in dogs.     

Effect of storage conditions on hemostatic parameters of canine plasma obtained for transfusion

OBJECTIVE: To evaluate the effects of various storage conditions on one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), and fibrinogen concentration of canine plasma collected for transfusion. SAMPLE POPULATION: Plasma from 9 dogs. PROCEDURE: Whole blood was collected from dogs by means of jugular venipuncture and centrifuged at 7,300 X g for 20 minutes at 0 C. A plasma extractor was then used to generate plasma. Aliquots of plasma were collected in segments of plastic tubing and in microcentrifuge tubes, and plasma collection bags, tubing segments, and microcentrifuge tubes were immediately frozen at -30 C. Additional tubing segments and microcentrifuge tubes were stored at 2 C. After 1 week of storage, all samples were thawed, and OSPT, APTT, and fibrinogen concentration were measured. Collection bags and microcentrifuge tubes were refrozen at -30 C, and values were measured again 30 days after blood collection. RESULTS: Values for OSPT, APTT, and fibrinogen concentration did not vary significantly with storage time, temperature, or container. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that storage for up to 30 days and at 2 C versus -30 C did not have any significant effect on hemostatic parameters of canine plasma obtained for transfusion.     

Influence of progesterone and pregnancy on canine fibrinogen values

Progesterone alone or in combination with oestrogen was given to male dogs and nonoestrous bitches by intramuscular injection. Progesterone produced a marked increase in plasma fibrinogen values. The fibrinogen response appeared to be independent of oestrogen administration. No alteration in haematocrit values, platelet count, APTT and OSPT results or the activities of coagulation factors VII, VIII and IX was observed following hormone administration. It is suggested that increased plasma progesterone concentrations may be partly responsible for the two- to three-fold increase in fibrinogen which occurs during gestation in the bitch.     

Changes in coagulation and fibrinolysis in horses during exercise

Changes in clotting time (CT) and fibrinolytic activity (FA) were evaluated in 6 mature, female horses during exercise. Two trials were performed on consecutive days, using a randomized crossover design. Each mare was assigned to either an exercise trial or a control trial on the first day, and to the alternate trial 24 hours later. Mares exercised for 20 minutes on a treadmill at an elevation of 2 degrees and a velocity of 5 m/s. Venous blood samples were collected immediately before exercise, at 4, 8, 12, 16 and 20 minutes during exercise, and 15 minutes after cessation of exercise. Blood was placed into plain glass tubes for determination of CT, and into chilled, citrated tubes for determination of FA, plasminogen/plasmin complex activity (PLG), one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), and antithrombin-III (AT-III) activity. There were significant differences (P less than 0.05) between the control and exercise groups for CT, FA, and PLG. During exercise, clotting time decreased from 21.5 +/- 1.6 minutes to 9.9 +/- 1.6 minutes (mean +/- SD; P less than 0.05), without significant changes in OSPT, APTT, or AT-III. Fibrinolytic activity and PLG increased (P less than 0.05) during exercise. Changes in CT, FA, and PLG were significant at 4 minutes of exercise, remained altered until the end of exercise, and returned to baseline values by 15 minutes of recovery. Clotting time, OSPT, APTT, FA, AT-III, and PLG did not change (P greater than 0.05) during control trials.     

Changes in blood coagulation parameters of red deer (Cervus elaphus) experimentally infected with malignant catarrhal fever

Changes in blood coagulation parameters were followed in four red deer (Cervus elaphus) experimentally infected with malignant catarrhal fever (MCF) of deer. Blood platelet counts, activated partial thromboplastin time (APTT), one-stage prothrombin time (OSPT), activated clotting time (ACT), plasma anti-thrombin III (ATIII) activity, fibrinogen degradation production (FDP) and fibrinogen levels were measured. Inoculated deer became pyrexic after 17 or 19 days. Thereafter they developed watery diarrhoea which rapidly became haemorrhagic. The course of the clinical disease ranged from four to six days before the animals were killed or died. All inoculated deer developed abnormalities in laboratory parameters of blood coagulation. These varied within and between animals, but the coagulation profiles of all four animals remained abnormal until death. Post-mortem findings included extensive systemic petechiation, severe haemorrhage in the alimentary canal and vasculitis with disseminated thrombosis. Abnormal coagulation parameters included extension of APTT and OSPT, increased FDP, decreased ATIII and platelet counts and increased fibrinogen levels. The increases in fibrinogen were compatible with the acute phase response. The other coagulation abnormalities and haemorrhage and thrombosis were indicative of disseminated intravascular coagulation (DIC) with consumption coagulopathy, ACT remained normal in all deer although final clot quality was considered poor.     

Coagulopathic Effects and Therapy of Brodifacoum Toxicosis in Dogs

The clinical signs and laboratory changes of brodifacoum (BDF) intoxicated dogs and their response to vitamin K1 treatment were examined. Brodifacoum, a second-generation anticoagulant rodenticide, was fed to four dogs for 3 consecutive days producing a cumulative dose of 1.1 mg BDF/kg body weight. Clinical observations of the animals were made daily throughout the study. Monitored laboratory parameters included: one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), activated coagulation time (ACT), complete blood counts, thrombocyte counts, and serum chemistry values. Response to vitamin K1 therapy was evaluated clinically and by laboratory tests. Serum BDF concentrations were monitored. Inappetence and hemorrhagic tendencies were exhibited by day 5 postrodenticide exposure. One-stage prothrombin time, APTT, and ACT were 25% greater than time zero values at 24, 24, and 72 hours postdosing, respectively. All laboratory parameters returned to normal within 48 hours of initiating vitamin K1 therapy (0.83 mg/kg orally, TID for 5 days). Serum brodifacoum concentrations were highest (1065-1215 ng/mL) during the 3 days after BDF dosing and were detectable (3.0-7.5 ng/mL) until day 24 postexposure. A mean BDF elimination half-life of 6 +/- 4 days was observed.     

Xenotransplantation of porcine pancreatic endocrine cells to total pancreatectomized dogs

Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups of 3 dogs each. In three dogs of the control group, exogenous insulin was administered twice a day for 30 weeks to maintain fasting blood glucose (FBG) levels within the normal range. The remaining three dogs were implanted with Bio-AEPs (implantation group), in addition to daily insulin administration. In the implantation group, Bio-AEPs containing 1.3 to 1.8 x 10(7) cells per kg of body weight of the recipient were implanted without fixation into the abdominal cavity. In the control group, exogenous insulin requirements did not decrease during the experimental period, whereas it significantly decreased for a certain period (3, 11, 17 weeks) after implantation in all implanted dogs. In the implantation group, laparotomy was performed after FBG and the exogenous insulin requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were completely destroyed, and the remaining one was encapsulated by thin fibrous tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia, of the PE-cells was observed on transmission electron microscopy. In conclusion, Bio-AEP could function for a certain period after implantation in this study. However, more preclinical researches should be needed to apply this technique for the treatment of diabetic dogs.     

Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987-1997)

OBJECTIVE: To determine usefulness of the test for proteins induced by vitamin K absence or antagonism (PIVKA) to identify anticoagulant-poisoned dogs, compared with one-stage prothrombin time (OSPT) and activated partial thromboplastin time (APTT) tests. DESIGN: Retrospective study. ANIMALS: 325 dogs. PROCEDURE: Comparisons of results of PIVKA, OSPT, and APTT measurements in dogs with anticoagulant poisoning, hepatic disease, disseminated intravascular coagulation, other blood-related disorders, immune-mediated diseases, or other chronic and acute diseases were performed. Median, quartile, and range values were determined. RESULTS: PIVKA tests with a 150-second critical value had > 98% specificity and > 90% sensitivity for diagnosis of anticoagulant poisoning versus > 99% specificity and > 79% sensitivity with a 300-second critical value. Comparison of PIVKA values among diagnostic groups revealed significant differences between dogs with anticoagulant poisoning and all other groups. CONCLUSIONS AND CLINICAL RELEVANCE: The PIVKA test with a 150-second critical value is diagnostically useful for distinguishing anticoagulant poisoning from other coagulopathies. Severe liver disease can cause false-positive results. Administration of vitamin K1 or early evaluation (within a few hours of ingesting anticoagulant) may cause false-negative results. Dogs with PIVKA test values > 150 seconds and clinical signs of anticoagulant poisoning can confidently be considered to have anticoagulant poisoning because of the high test sensitivity and specificity.     

Exfoliative cutaneous lupus erythematosus in German shorthaired pointer dogs: disease development,progression and evaluation of three immunomodulatory drugs (ciclosporin,hydroxychloroquine, and adalimumab) in a controlled environment

Six German shorthaired pointer dogs (two females, four males) with exfoliative cutaneous lupus erythematosus (ECLE) were studied in a controlled setting until disease progression necessitated euthanasia. During investigations into the heredity of disease, five dogs received immunomodulatory drugs to alleviate clinical signs (lameness, erythema, scaling, erosions/ulcers). One dog served as a control and received only baths and oral fatty acids. Four dogs received ciclosporin (5–10 mg/kg once daily) for 4.5 months to 2 years. Ciclosporin decreased erythema and arthralgia, but did not halt worsening of lesions. Three dogs received hydroxychloroquine (5–10 mg/kg once daily) for 8 weeks, 7 months, and 9 months, respectively, with no side effects. Hydroxychloroquine appeared to slow clinical progression in two dogs on extended treatment and normalized globulin levels in all three dogs while receiving the drug. Four dogs, including the control dog, were euthanized between 1 and 4.5 years of age. Two remaining male dogs received a tumour necrosis factor (TNF)‐α antagonist, adalimumab, at 0.5 mg/kg every 2 weeks for 8 weeks then weekly for 8 weeks. Serum TNF‐α levels were not significantly altered nor were quantifiable changes seen in skin lesions or lameness. Subsequently, the dogs were maintained on hydroxychloroquine for another year. This is the first study to evaluate the use of a TNF‐α inhibitor for canine lupus and the first to address the safety of long‐term administration of hydroxychloroquine, albeit in a small number of dogs. The study documents the progression of ECLE and generally poor response to therapy.     

Postoperative bleeding in retired racing greyhounds

BACKGROUND: Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively. Hypothesis: Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding. ANIMALS: Eighty-eight RRG undergoing ovariohysterectomy or castration. METHODS: All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA-100(a); fibrinogen, d-dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age- and sex-matched control group of RRG. RESULTS: Twenty-six percent of the dogs had bleeding 36-48 hours after surgery. AP (P <.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P <.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit. CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.     

Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The one- and two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.     

Presentation,clinical pathological and post‐mortem findings in three related Scottish terriers with ligneous membranitis

Ligneous conjunctivitis and gingivitis were diagnosed in three related Scottish terrier dogs presented for investigation of severe conjunctivitis and respiratory signs. Hypoplasminogenaemia was confirmed in one of the three affected dogs. Supportive treatment was not effective, and the dogs died or were euthanased because of the disease. Post‐mortem analysis of two of the dogs revealed multiple abnormalities including severe proliferative fibrinous lesions affecting the conjunctiva, gingiva, trachea, larynx and epicardium and multiple fibrous adhesions throughout the thoracic and abdominal cavities. One dog had internal hydrocephalus and lacked a cerebellar vermis. Ligneous membranitis was confirmed on histopathology. This is a rare condition in dogs but an important differential diagnosis for severe conjunctivitis and gingivitis.     

Effect of oral administration of unfractionated heparin (UFH) on coagulation parameters in plasma and levels of urine and fecal heparin in dogs

The effects of heparin administration, by the oral route, were evaluated in dogs. In single and multiple dose studies (single 7.5 mg/kg, multiple 3 × 7.5 mg/kg per 48 h), plasma, urine, and fecal samples were collected at various times up to 120 h after oral administration of unfractionated heparin. Changes in plasma and urine anti-Xa activity, plasma and urine anti-IIa activity, plasma activated partial thromboplastin time (APTT) and antithrombin (ATIII), and chemical heparin in urine and feces were examined with time. There was support for heparin absorption, with significant differences in APTT, heparin in plasma as determined by anti-Xa activity (Heptest) in the single dose study and plasma anti-Xa activity, anti-IIa activity and ATIII; and chemical heparin in urine in the multiple dose study. No clinical evidence of bleeding was detected in any dog during the studies. Oral heparin therapy may be applicable for thromboembolic disease in animals. Further studies are warranted to determine the effects of oral heparin at the endothelial level in the dog.     

Hepatotoxicosis in dogs consuming a diet of camel meat contaminated with indospicine

Background Four dogs presented with clinical signs of severe hepatic disease after consuming a commercial camel meat diet. Methods Laboratory investigation revealed evidence of severe liver disease, including markedly increased serum alanine aminotransferase (ALT) activity and total bilirubin concentration, and prolonged clotting times. Results Two dogs deteriorated despite supportive therapy and were euthanased. Histologically, both livers appeared similar, with the main lesion being extensive periacinar necrosis and haemorrhage. Indospicine, a toxic amino acid of plant origin, was detected in the serum and/or plasma from all four dogs, as well as in tissues of a dog that was necropsied and in a sample of the camel meat fed to this animal. Serum biochemistry tests using blood samples collected from 15 additional dogs identified as having eaten the diet detected indospicine was in the serum of 14 and 3 had increased ALT activity. One of the latter dogs subsequently developed clinical signs of severe liver disease and was euthanased. Conclusion To the authors' knowledge, this is the first published report of the detection of indospicine residues in camel meat and the occurrence of severe, sometimes fatal, liver disease in dogs that consumed this contaminated meat.     

Effects of administration of glucocorticoids and feeding status on plasma leptin concentrations in dogs

OBJECTIVE: To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs. ANIMALS: 20 nonobese dogs. PROCEDURE: For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly. RESULTS: For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.     

Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs

CASE DESCRIPTION: 8 adult dogs were evaluated for treatment of lethargy and vomiting after ingestion of xylitol, a sugar alcohol used as a sweetener in various products. CLINICAL FINDINGS: In addition to vomiting and lethargy, 5 of the dogs had widespread petechial, ecchymotic, or gastrointestinal tract hemorrhages. Common clinicopathologic findings included moderately to severely high serum activities of liver enzymes, hyperbilirubinemia, hypoglycemia, hyperphosphatemia, prolonged clotting times, and thrombocytopenia. Necropsies were performed on 3 dogs and severe hepatic necrosis was found in 2. In the third dog, histologic examination revealed severe hepatocyte loss or atrophy with lobular collapse. TREATMENT AND OUTCOME: Treatments varied among dogs and included IV administration of fluids; plasma transfusions; and, if indicated, administration of dextrose. Three dogs were euthanatized, 2 dogs died, 2 dogs made a complete recovery, and 1 dog was recovering but was lost to follow-up. CLINICAL RELEVANCE: Although xylitol causes hypoglycemia in dogs, hepatic failure after ingestion has not previously been reported. Because an increasing number of consumer products contain xylitol, clinicians should be aware that ingestion of xylitol can have serious, life-threatening effects.     

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs

Objective To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia.
Design A prospective study involving nine normal male dogs and seven with prostatic hyperplasia.
Procedure Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcuta-neously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals.
Results A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations.
Conclusion Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hyper-somatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.     

An open-label, dose-escalating phase I study of elsamitrucin (SPI 28090) in treatment of malignant solid tumors in dogs

Background: Elsamitrucin, the most potent topoisomerase II inhibitor available, is unique in that it does not cause neutropenia or cardiotoxicosis. It has antitumor activity in human patients with relapsed or refractory non‐Hodgkin's lymphoma. Objectives: To determine the maximum tolerated dose (MTD), safety, and toxicity of elsamitrucin when administered to tumor‐bearing dogs and to evaluate the incidence and severity of adverse events. Animals: Twenty client‐owned dogs with spontaneous malignant solid tumors or lymphoma that were refractory to, or for which the owner declined, conventional therapy were enrolled. Methods: Prospective, open‐label, single‐agent study. Escalating doses of elsamitrucin were administered once weekly IV for up to 16 weeks in a modified 3 + 3 Phase I design. The starting dose was 0.06 mg/kg with escalation to 0.08 and 0.09 mg/kg. Dogs that remained on the study were monitored for evidence of toxicoses for at least 4 weeks and for survival every 2 months. Results: Serious adverse events (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart failure and another developed hepatotoxicosis manifested by increased alanine aminotransferase, alkaline phosphatase, and total bilirubin (0.06 mg/kg dose); 1 dog developed severe anorexia and diarrhea, another developed severe diarrhea alone, and a 3rd dog went into cardiac arrest (0.09 mg/kg dose). A dose of 0.08 mg/kg was well tolerated with no SAEs. Conclusions and Clinical Importance: The MTD and recommended dose for Phase II trials of elsamitrucin is 0.08 mg/kg IV weekly. Elsamitrucin might be considered for combination protocols with myelosuppressive chemotherapy agents.     

Comparison of two insulin protocols for diabetic dogs undergoing cataract surgery

Objective To evaluate the effectiveness of two insulin doses to maintain an acceptable range of blood glucose concentrations (70–200 mg dL^?1) in the peri‐operative period in diabetic dogs. Animals Twenty‐four diabetic dogs with a median weight of 20.6 kg and a median age of 8 years old. Methods The dogs were randomly assigned to receive either 25 or 100% of their normal insulin dose subcutaneously on the morning of surgery. The anesthetic and feeding protocols were standardized. On the day before surgery, venous blood was collected for measurement of β‐hydroxybutyrate, cholesterol, glucose, glycosylated hemoglobin, hematocrit, total plasma protein and urea nitrogen. On the day of surgery, blood glucose concentrations were measured prior to anesthesia, prior to the start of surgery, 1 and 2 hours after beginning of surgery, 1 hour after extubation, at 16 : 00 hours and at 20 : 00 hours. β‐hydroxybutyrate concentrations were measured at 20 : 00 hours that day. At 08 : 00 hours the following day, β‐hydroxybutyrate and glucose concentrations were measured. The significance of differences between groups was tested with Wilcoxon's two‐tailed rank‐sum test, Chi‐square test and Fisher's exact test. Results There were no differences in insulin treatments, clinical signs, concurrent diseases and most clinicopathological parameters between the two groups of dogs at entry to the study. The 25% dose group had blood glucose values of 296 (102–601) mg dL^?1 at 16 : 00 hours and 429 (97–595) mg dL^?1 at 20 : 00 hours on the day of surgery. The 100% insulin dose group had lower corresponding values of 130 (55–375) mg dL^?1 (p = 0.04) and 185 (51–440) mg dL^?1 (p = 0.004). No other differences (p < 0.05) were detected between the two groups. Conclusions The administration of a full dose of insulin is only marginally advantageous for reducing glucose to normal (70–120 mg dL^?1) after anesthesia but neither dose consistently induced glycemic values in an acceptable range (70–200 mg dL^?1) or normoketonemia. Clinical relevance Blood glucose should be measured immediately before anesthesia and periodically throughout the peri‐operative period in all diabetic dogs because presurgical subcutaneous administration of 25 or 100% of the normal insulin dose resulted in unpredictable blood glucose concentrations.     

Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for canine transitional cell carcinoma

As a prelude to photodynamic therapy, 5‐aminolevulinic acid (ALA) was given orally to healthy dogs. ALA‐induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose‐dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA‐based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA‐based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA‐based PDT resulted in tumour progression‐free intervals from 4 to 34 weeks in five dogs; one dog with pre‐existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.