Combination Allopurinol and Antimony Treatment versus Antimony Alone and Allopurinol Alone in the Treatment of Canine Leishmaniasis (96 Cases)

The aim of the present study was to evaluate the long-term clinical outcome for dogs with leishmaniasis that were treated with 3 different protocols: combined treatment with antimony and allopurinol, antimony alone, or allopurinol alone. Ninety-six dogs included in this study were determined to have leishmaniasis on the basis of (1) clinical features, (2) identification of the parasite in smears of lymph node, bone marrow aspirates, or skin biopsies, and (3) specific immunofluorescent assay. Three groups of dogs were defined: 45 dogs (group 1) were treated with antimony (100 mg/kg s.c. q24h) given concurrently for 1 month with allopurinol (15 mg/kg p.o. q12h), and then allopurinol alone for 8 months at the same dosage; 40 dogs (group 2) were treated with antimony alone according to the manufacturer's instructions (200 mg/kg s.c. q24h at 2-day intervals for 3-6 months); and 11 dogs (group 3) were treated with allopurinol alone (15 mg/kg p.o. q12h for 1-20 months). Information concerning signalment, history, physical examination findings, serologic testing and number of dogs becoming seronegative, outcome for each treated dog (clinical cure versus failure), and long-term survival were recorded. The numbers of the clinical cures versus failures were significantly different among the 3 groups (chi2 = 17.77, P < .001), between groups 1 and 2 (chi2 = 8.02, P < .01), between groups 2 and 3 (chi2 = 11.00, P < .01), and between groups 1 and 3 (chi2 = 16.52, P < .001). No significant difference between groups 1 and 2 was noted in the type of failure (relapse or death), serologic test results, and number of survival years (chi2 = 2.79, P > .05). The results of the present study indicate that antimony in combination with allopurinol produces better results than antimony alone or allopurinol alone for the treatment of the canine leishmaniasis. With combination treatment, duration of treatment with antimony is shorter and long-term administration of allopurinol is well tolerated.     

Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and sodium stibogluconate

Seven dogs with parasitologically proven clinical visceral leishmaniosis (Leishmania infantum infection) were treated with a combination of allopurinol and sodium stibogluconate. The dogs received first orally 15 mg/kg of allopurinol every 12 h until the clinical signs improved, in the following 1 month period allopurinol at same dose and subcutaneously 30 mg/kg of sodium stibogluconate combination were given daily and at the end of the combined treatment, allopurinol was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly (P < 0.001) lower compared with pretreatment, IFAT-titers of dogs were still positive. No relapses occurred during treatment period and a 6-24-month duration after the end of therapy. Based on the above results, long-term use of allopurinol combined with sodium stibogluconate together with support treatment concluded to have enough therapeutic efficacies in the treatment of dogs with visceral leishmaniosis. Observations of the cases for possible relapses were still going on and insecticide application was carefully carrying on in order preventing a possible re-infection.     

Use of allopurinol for maintenance of remission in dogs with leishmaniasis

Current treatments for infected dogs with leishmaniasis do not always provide long-term control of the disease and clinical relapses are common. In this study, the usefulness of long-term allopurinol administration in the maintenance of clinical remission in canine leishmaniasis was evaluated. Fifteen dogs with natural leishmania infection were subjected to an initial treatment based on the simultaneous administration of meglumine antimoniate (100 mg/kg/day) and allopurinol (30 mg/kg/day). Once clinical remission was achieved, a maintenance treatment with allopurinol (20 mg/kg/day) administered for one week a month was instituted. Results were compared with those of a retrospective control group comprising 15 infected dogs which only followed the induction treatment. Relapses occurred in 86 per cent of control dogs within 14 months of discontinuing treatment. In contrast, those dogs on intermittent oral allopurinol administration were successfully maintained in clinical remission for a follow-up period of 10 to 44 months. In this latter group, specific antibody titres decreased or were unchanged, no side effects directly attributable to allopurinol were seen and treatment was well accepted by the owners. It is concluded that long-term intermittent administration of allopurinol is an effective way of maintaining clinical remission in dogs with leishmaniasis.     

Serum concentrations of acute-phase proteins in dogs with leishmaniosis during short-term treatment

OBJECTIVE: To evaluate changes in serum concentrations of acute-phase proteins in dogs with leishmaniosis during short-term therapy in accordance with 2 treatment protocols and determine whether concentrations of acute-phase proteins could be used to monitor the initial response of dogs to treatment. ANIMALS: 12 dogs naturally infected with Leishmania infantum. PROCEDURE: Dogs were allocated into 2 groups. Dogs of group 1 were treated by use of meglumine antimonate (100 mg/kg, SC, q 24 h) administered concurrently with allopurinol (15 mg/kg, PO, q 12 h) for 20 days and then with allopurinol alone at the same dosage for the subsequent 30 days. Dogs of group 2 were treated by administration of allopurinol alone (15 mg/kg, PO, q 12 h) for 60 days). Blood samples were obtained before and during treatment for measurement of serum concentrations of acute-phase proteins and determination of CBC counts, serum biochemical analyses, and electropherograms. RESULTS: All dogs evaluated in the study had increased concentrations of C-reactive protein, haptoglobin, and ceruloplasmin at the time of diagnosis of leishmaniosis. Mean concentration of serum amyloid A before treatment was also increased, but some of the dogs had concentrations of serum amyloid A that were within the reference range. Concentrations of C-reactive protein and ceruloplasmin decreased significantly in all dogs at the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of concentrations of selected acute-phase proteins, such as C-reactive protein or ceruloplasmin, could be used to evaluate the initial response of dogs with leishmaniosis to treatment.     

Study of efficacy of miltefosine and allopurinol in dogs with leishmaniosis

Visceral leishmaniosis is a life-threatening disease of medical, social and economic importance in endemic areas. It is an opportunistic infection in immunocompromised patients, including human immunodeficiency virus-positive subjects. Dogs are the main reservoir of Leishmania infantum. The aim of this study was to evaluate the efficacy of miltefosine and allopurinol for the control of human leishmaniosis using the dog as a model. The study included 28 sick dogs treated with miltefosine (2 mg/kg/day PO) administered concurrently with allopurinol (10 mg/kg/day, PO) for 30 days, and then with allopurinol alone, at the same dosage, for 1 year. Eight dogs (four of which relapsed) received a second cycle of miltefosine within 6 months of the first cycle. Efficacy was measured by real-time polymerase chain reaction assay on whole blood samples and lymph node aspirates, collected at baseline and every 3 months for 12 months. Of the total number of animals (28), two showed renal insufficiency and died after the start of therapy with miltefosine. Two other dogs presented some side effects to treatment, such as nausea, vomiting and reduction in white and red blood cell counts, and these animals were excluded from the follow-up. The results showed that the first cycle of therapy with miltefosine and allopurinol induced a drastic and progressive reduction of L. infantum load in lymph node aspirates but the second cycle did not eliminate the parasite.     

Clinical, Serologic, and Parasitologic Follow-Up after Long-Term Allopurinol Therapy of Dogs Naturally Infected with Leishmania infantum

Canine leishmaniasis usually is treated with antimony compounds, but frequent relapses, adverse effects, high costs, and development of resistance to long-term antimonial therapy emphasize the importance of searching for alternative antileishmanial drugs. Allopurinol was used at a dosage of 10 mg/kg/day PO to treat 10 dogs naturally infected with Leishmania infantum for a period of 2-24 months. Nine dogs recovered within 2-6 months of chemotherapy, and no relapses were observed during the treatment of up to 20 months. However, 3 of 4 dogs relapsed after treatment was discontinued. These dogs again recovered clinically when therapy was resumed. Parasite-specific immunoglobulin concentrations (IgG2) were high in all dogs before therapy and remained high even in clinically cured dogs during or after therapy. On the other hand, specific IgG1 reactions, which have been shown to be detectable in symptomatic animals, persisted in 7 dogs for long periods after clinical recovery. Three of these dogs relapsed within 2-4 weeks after interrupting therapy. However, 1 dog with no detectable specific IgG1 reaction at the end of therapy did not relapse in the following 4 months. Parasites could be detected in 8 of 9 dogs after clinical improvement by in vitro cultivation or polymerase chain reaction (PCR) testing of lymph node aspirates. In 4 of these dogs, parasites also were detected in blood samples by PCR. Hence, these clinically cured dogs must be regarded as reservoirs of Leishmania and allopurinol cannot be recommended in endemic areas.     

Evaluation of the efficacy and safety for use of two sedation and analgesia protocols to facilitate assisted ventilation of healthy dogs

OBJECTIVE: To determine the effectiveness and safety of 2 sedative-analgesic protocols to facilitate assisted ventilation in healthy dogs. ANIMALS: 12 healthy dogs. PROCEDURES: Dogs were randomly assigned to 2 groups. Mean dosages for protocol 1 were diazepam (0.5 mg/kg/h [n = 3 dogs]) or midazolam (0.5 mg/kg/h [3]), morphine (0.6 mg/kg/h [6]), and medetomidine (1.0 microg/kg/h [6]). Mean dosages for protocol 2 were diazepam (0.5 mg/kg/h [n = 3]) or midazolam (0.5 mg/kg/h [3]), fentanyl (18 microg/kg/h [6]), and propofol (2.5 mg/kg/h [6]). Each dog received the drugs for 24 consecutive hours. All dogs were mechanically ventilated with adjustments in minute volume to maintain normocapnia and normoxemia. Cardiorespiratory variables were recorded. A numeric comfort score was assigned hourly to assess efficacy. Mouth care, position change, and physiotherapy were performed every 6 hours. Urine output was measured every 4 hours. RESULTS: Use of both protocols maintained dogs within optimal comfort ranges > 85% of the time. The first dog in each group was excluded from the study. Significant decreases in heart rate, oxygen consumption, and oxygen extraction ratio were evident for protocol 1. Cardiac index values in ventilated dogs were lower than values reported for healthy unsedated dogs. Oxygen delivery, lactate concentration, and arterial base excess remained within reference ranges for both protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Use of both protocols was effective for facilitating mechanical ventilation. A reduction in cardiac index was detected for both protocols as a result of bradycardia. However, oxygen delivery and global tissue perfusion were not negatively affected.     

The safety of dirlotapide in dogs

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin-of-safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well-tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20–40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide-treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.     

Real-time PCR assay in Leishmania-infected dogs treated with meglumine antimoniate and allopurinol

A real-time PCR assay was exploited for monitoring the Leishmania DNA load in different tissues from 18 naturally-infected dogs before and after treatment with a combination of meglumine antimoniate (100mg/kg/day, subcutaneously) and allopurinol (10mg/kg/day, orally) for 30 days. After the combined therapy, allopurinol was continued at the same dose until the end of the observation period. Whole blood samples, lymph node aspirates, and skin biopsies were collected at the time of diagnosis, 1 month after starting therapy, and every 3 months for 2 years. In six dogs parasite load assessments continued every 6 months for a further 3 years. At each assessment, the dogs were examined for signs of disease and a clinical score was recorded. At diagnosis, the highest Leishmania DNA load was detected in lymph node aspirates. From 1-6 months post-therapy a general improvement in clinical conditions was recorded in all dogs, which correlated with a decrease in the parasite DNA load in all tested tissues, even though it was less pronounced in lymph node aspirates. In the period from 9-24 months post-therapy, a re-increase in parasite load was observed in the tissues of some dogs, concomitant with a disease relapse. The results show that the combined therapy with meglumine antimoniate and allopurinol promoted a clinical improvement which was accompanied by a reduction in the parasitic load in the blood, skin and lymph nodes but, even after long period of allopurinol administration alone, Leishmania may persist in dog tissues.     

Use of prostaglandins and bromocriptine mesylate for pregnancy termination in bitches

OBJECTIVE: To assess the efficacy and safety of 2 protocols using bromocriptine mesylate and prostaglandins to terminate unwanted pregnancy in bitches. DESIGN: Prospective randomized single-blind controlled study. ANIMALS: 34 crossbred and purebred bitches referred for possible pregnancy termination. Seven additional pregnant bitches were used as controls. PROCEDURE: Pregnancy was assessed by ultrasonographic examination from day 25 after mating in all bitches. Of the 34 bitches, 25 were pregnant and were randomly allocated to a treatment group. Group-1 dogs (n = 12) received a combination of increasing amounts of bromocriptine mesylate (15 to 30 microg/kg [6.8 to 13.6 microg/lb], p.o., q 12 h) and dinoprost tromethamine (0.1 to 0.2 mg/kg [0.045 to 0.09 mg/lb], s.c., q 24 h). Group-2 dogs (n =13) received a combination of increasing amounts of bromocriptine mesylate (the same schedule as group-1 dogs) and cloprostenol sodium (1 microg/kg [0.45 microg/lb], s.c., q 48 h). Both groups were treated until pregnancy termination. Results-Treatment success was 100% in both groups. Days of treatment required for pregnancy termination did not significantly differ between groups (5.0 +/- 0.6 vs 3.7 +/- 0.6 days, group-1 and group-2 dogs, respectively) although adverse effects only developed in group-1 dogs. At the end of the protocols, pseudopregnancy was observed in 3 of 12 and 6 of 13 group-1 and group-2 dogs, respectively. Pregnancy termination was followed by a mucoid sanguineous vulvar discharge for 3 to 10 days. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicate that protocols that combine the use of bromocriptine mesylate and prostaglandins for the termination of unwanted pregnancy in bitches are efficient and safe. The use of bromocriptine mesylate and cloprostenol had the best results and could be easily used on an outpatient basis.     

Epidural vs. Intramuscular Oxymorphone Analgesia after Thoracotomy in Dogs

Oxymorphone was administered epidurally (0.1 mg/kg) or intramuscularly (IM) (0.2 mg/kg) to 16 dogs undergoing thoracotomy, to compare the analgesic effectiveness. Heart rate, respiratory rate, systolic and diastolic blood pressure, and pain score were measured hourly. Arterial blood gases were measured at hour 1. A single dose of oxymorphone injected epidurally provided analgesia for up to 10 hours, whereas the IM route provided a comparable effect for less than 2 hours. There were statistically significant increases in heart rate, and systolic and diastolic blood pressures at hour 2 in the dogs treated IM over the dogs treated epidurally. We conclude that epidurally administered oxymorphone is highly effective in alleviating pain after thoracotomy in dogs and provides longer lasting analgesia than the IM route.     

Effects of allopurinol treatment on the progression of chronic nephritis in Canine leishmaniosis (Leishmania infantum)

Forty dogs with canine leishmaniosis (CL) participated in this study, which was designed to investigate the effect of allopurinol on the progression of the renal lesions associated with this disease. The animals were allocated into 5 groups. Group A dogs (n = 12) had neither proteinuria nor renal insufficiency, group B dogs (n= 10) had asymptomatic proteinuria, and group C dogs (n = 8) were proteinuric and azotemic. Two more groups, CA and CB, comprising 5 dogs each, served as controls for groups A and B, respectively. Group A, B, and C dogs received allopurinol PO (10 mg/kg q12h) for 6 months, whereas group CA and CB dogs were placebo-treated. Serum biochemistry profile, urinalysis, urine protein/creatinine ratio, and glomerular filtration rate (GFR) measurements were carried out at the beginning of the study, the 3rd month, and the 6th month, whereas renal biopsies were carried out only at the beginning and the end of the trial. Membranoproliferative glomerulonephritis was the most common cause of chronic renal failure. Mesangioproliferative and tubulointerstitial nephritis were detected even in group A and CA dogs. Allopurinol not only lowered proteinuria in group B dogs but also prevented the deterioration of GFR and improved the tubulointerstitial, but not the glomerular, lesions in both group A and group B dogs. Further, it resolved the azotemia in 5 of the 8 dogs admitted with 2nd stage chronic renal failure (group C). Consequently, treatment with allopurinol is advisable in CL cases with asymptomatic proteinuria or 1st-2nd stage chronic renal failure.     

Cyclosporin and ketoconazole interaction for treatment of perianal fistulas in the dog

OBJECTIVE: To assess the use of concurrent ketoconazole and low dose cyclosporin administration in a group of dogs with clinical evidence of perianal fistulas, and to determine if this combination could be used to manage perianal fistulas effectively. DESIGN: Prospective clinical trial PROCEDURE: Sixteen dogs with clinical evidence of perianal fistulas were given ketoconazole (10 mg/kg once daily) and cyclosporin (1 mg/kg twice daily initially) for 16 weeks. Blood cyclosporin assays were performed regularly and cyclosporin doses were altered to achieve a stable blood level above 200 ng/mL. Regular examinations assessed the dogs' general health, changes in clinical behaviour, fistula size and number. A complete blood count and serum biochemical analysis was performed in all dogs before and after the treatment period, and after 8 weeks of treatment in 12 dogs. Dogs were assessed for recurrence of lesions at 1, 3 and 12 months after the trial. RESULTS: All dogs showed marked improvement in lesions and behaviour within 14 days of the medication. Fourteen dogs completed the trial. Two dogs were excluded due to concurrent disease. Thirteen dogs (93%) showed complete resolution of fistulas during the treatment period. Seven dogs (50%) had no recurrence after 12 months. Recurrence was seen in three dogs (21%) at 8, 10 and 12 months after treatment, and in three dogs (21%) within 1 month of treatment. The medication was well tolerated. Side effects included transient anorexia, vomiting and lethargy in some dogs, increased shedding of hair and gingival hyperplasia. Ketoconazole administration allowed a dramatic reduction in cyclosporin dose (over 90% in 12 dogs and 80% in the other two) compared to previously reported cases treated with cyclosporin alone. CONCLUSION: The use of combined ketoconazole and cyclosporin provided an effective treatment for perianal fistulas. Outcomes were similar to those seen with cyclosporin alone, but allowed a significant reduction in cyclosporin dose and, therefore, cost. The use of immunosuppressive therapy in the treatment of perianal fistulas was effective and avoided many of the problems associated with surgical treament.     

Evaluation of the analgesic effect of lidocaine and bupivacaine used to provide a brachial plexus block for forelimb surgery in 10 dogs

Twenty adult dogs weighing between 1.4 and 53.5 kg and aged between six months and nine years were anaesthetised and the brachial plexus was localised with the aid of a nerve stimulator. In 10 of the dogs a brachial plexus block was induced with a mixture of lidocaine and bupivacaine and the other 10 each received 0.25 ml/kg saline as a control. The end-tidal isoflurane concentration was maintained between 1.3 and 1.4 per cent during surgery for carpal arthrodesis or a fracture of the radius or ulna. Acute heart rate or blood pressure increases of 20 per cent or more were treated with 1 microg/kg fentanyl intravenously. Postoperatively, signs of pain were scored by a single blinded observer at hourly intervals until eight hours after the block had been induced, on a scale from 0 to 18. Dogs with pain scores above 5 received 0.1 to 0.2 mg/kg methadone intravenously, repeated as necessary. During surgery the control dogs received significantly more fentanyl (median 0.05 microg/kg/minute, range 0.02 to 0.20 microg/kg/minute) than the group given local anaesthetic (median 0 microg/kg/minute, range 0 to 0.02 microg/kg/minute). Postoperatively, the control group required significantly more methadone (median 0.2 mg/kg, range 0.1 to 1 mg/kg) than the treated group (median 0 mg/kg, range 0 to 0.13 mg/kg).     

Initial and long-term efficacy of a lipid emulsion of amphotericin B desoxycholate in the management of canine leishmaniasis

Sixteen dogs in which canine leishmaniasis (CL) was diagnosed by positive identification of Leishmania amastigotes in bone marrow samples were treated with a mixture of amphotericin B (AmB) desoxycholate in soybean oil. To prevent the toxicity of AmB, dogs were pretreated with saline (50 mL/kg) and mannitol (2 g/kg). Dogs were treated twice weekly with an increasing dosage of amphotericin (0.8-2.5 mg/kg) for between 8 and 10 sessions. Transient adverse effects (anorexia, vomiting, or both) appeared in 81% of the dogs during therapy. At the end of the course, all dogs were clinically cured, with no parasites observed in bone marrow smears. Six of the 16 dogs (38%) were positive by polymerase chain reaction (PCR) in bone marrow samples at some stage of their follow-up, but only 2 were positive at the first test after treatment, which was performed within 5 months after the end of the therapy. The other 4 dogs were initially negative and became PCR-positive at subsequent examinations. Three of these 6 dogs also experienced a clinical relapse. Four dogs had at least 3 consecutive negative PCR tests during a minimum period of 18 months and were clinically cured. The results of the present study indicate that despite having a high initial effectiveness in the treatment of CL, relapses can occur with the described protocol. Also, a single negative PCR result in a recently treated dog cannot be interpreted as a complete cure.     

THE EFFECTIVENESS OF LEVAMISOLE HYDROCHLORIDE IN THE TREATMENT OF ADULT DIROFILARIA IMMITIS

Dogs infected with D. immitis were treated with oral levamisole hydrochloride at various dose rates over different durations. Clinical toxicity, haematological and biochemical parameters, body weight and food intake were recorded and filarial mortality estimated at autopsy. All filariae were dead in dogs treated at 10 mg/kg body weight twice daily (12 hourly) for 14 days, with minimal clinical toxicity being seen during the treatment period.     

Low-dose ethanol in the treatment of ethylene glycol poisoning

A pharmacokinetic study was conducted to determine the effectiveness of lower doses of ethanol in the treatment of ethylene glycol (EG) poisoning. Four dogs were maintained at serum ethanol concentrations of 0, 35 and 140 mg/dl prior to EG (i.v., 2 ml/kg) administration. The serum EG concentration-time data showed that the 35 mg/dl ethanol level provided as effective an inhibition of EG metabolism as did the 140 mg/dl level. The average urinary excretion rate of oxalic acid post EG administration was reduced to control levels by ethanol. The 35 mg/dl serum ethanol level reduced the total body clearance of EG from 93.9 to 50.0 ml/h/kg and increased the effective half-life from 5.78 to 11.4 h. Clinical testing was accomplished by giving the dogs 12 ml EG/kg body weight orally. One hour later, the dogs were either not treated or treated with a sodium bicarbonate-ethanol solution to obtain a serum ethanol concentration of 50 mg/dl. The clinical test performed in the ethanol-treated dogs showed little change from normal limits. Urine calcium oxalate crystals were seldom found. The dogs given EG (12 ml/kg) but not treated with ethanol were in a coma at 13 h and showed severe metabolic acidosis, dehydration, mild hepatocellular disease and acute renal damage. Urine calcium oxalate crystals were found in high numbers. The rapid death associated with EG poisoning appeared to be due to metabolic acidosis in combination with dehydration.     

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.     

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.     

Evaluation of once daily treatment with cyclosporine for anal furunculosis in dogs

Twenty-four dogs with anal furunculosis were treated with cyclosporine once daily for 13 weeks at dosages of 1.5, 3.0, 5.0 or 7.5 mg/kg, and re-examined after six and 12 months. After 13 weeks the disease in six of the dogs was in remission, 11 were controlled or improved and seven had failed to respond. The response of the dogs given the highest dose was significantly better than the response of the other groups taken together (P < 0.014), and better than the responses of the groups given 1.5 mg/kg and 5 mg/kg (P < 0.05). The dogs improved clinically during the treatment, most rapidly during the first five weeks. Of the six dogs that were in remission after 13 weeks, three relapsed after one, two and six months. The 11 dogs that were improved or controlled after 13 weeks were either left untreated or were continued on cyclosporine medication for one to three months at a dosage of 1.5 to 7.5 mg/kg; the disease went into remission in four cases and remained controlled in the other seven, but four of the 11 cases relapsed during the 12 months following the treatment. The side effects observed included increased coat turnover and transient vomiting.