Treatment of 46 cats with porcine lente insulin--a prospective, multicentre study

This prospective, multicentre, non-blinded, open study followed 46 cats with diabetes mellitus during treatment with porcine lente insulin (also known as porcine insulin zinc suspension, Caninsulin, Intervet) for 16+/-1 weeks (stabilization phase), with additional monitoring of some cats (n=23) for a variable period. At least three of the following were present at initial presentation: appropriate history of clinical signs consistent with diabetes mellitus, glucosuria, blood glucose greater than 15 mmol/l and fructosamine greater than 380 micromol/l. Insulin treatment was started at a dose rate of 0.25-0.5 IU/kg body weight twice daily, with a maximum starting dose of 2 IU/injection. Twenty-eight of the cats were classed as reaching clinical stability during the study, in 23 of these cats this was during the stabilization phase. Seven cats went into remission during the stabilization phase and one of the cats in week 56. Clinical signs of hypoglycaemia, significantly associated with a dose of 3 units or 0.5 IU/kg or more per cat (twice daily), were observed in nine of the 46 cats during the stabilization phase and concomitant biochemical hypoglycaemia was recorded in most cases. Biochemical hypoglycaemia, recorded in 6% of the blood glucose curves performed during the stabilization phase, was significantly associated with a dose rate of 0.75 IU/kg or more twice daily. This further highlights the need for cautious stepwise changes in insulin dose. The protocol used in the present study is suitable for and easy to use in practice. This study confirmed the efficacy and safety of porcine lente insulin (Caninsulin) in diabetic cats under field conditions.     

Insulin glargine has a long duration of effect following administration either once daily or twice daily in divided doses in healthy cats

The pharmacological effects of glargine administered once or twice daily were compared in six healthy cats. A two-way crossover study was performed with insulin and glucose concentrations measured following subcutaneous administration of glargine once daily (0.5U/kg) or twice daily (0.25U/kg, repeated after 12h). Nadir glucose concentration and mean daily glucose concentration did not differ significantly following insulin administration once daily or twice daily in divided doses. Time to reach last glucose nadir differed, with longer intervals occurring following twice daily dosing. Blood glucose failed to return to baseline concentration by 24h in three of six cats in each treatment group. Insulin variables were not significantly different following once or twice daily dosing. This study in healthy cats demonstrates that glargine has a long duration of action with carry-over effects to the next day likely, regardless of dosing regimen. A study in diabetic cats is required to determine the best dosing regimen.     

Management of feline diabetes mellitus.

Up to one quarter of diabetic cats can be well controlled with oral hypoglycemic drugs, although at least 75% require insulin therapy. Most available insulins provide good clinical control but only moderate glycemic control. Because mild to moderate hyperglycemia is well tolerated by cats receiving insulin but hypoglycemia can be life threatening, conservative insulin dosing is recommended. Clinical signs and water intake indicate whether a dose adjustment is required, but serial blood glucose measurements are usually needed to determine the direction of the adjustment. Starting doses of 0.3 to 0.5 IU/kg administered twice daily (rounded down to the nearest whole unit) are usually safe. Dose adjustments should not exceed 1 IU per cat every 2 to 4 weeks unless clinical hypoglycemia has occurred. Cats with clinical hypoglycemia need to be reassessed to see if they are in remission. If not, a 50% to 75% reduction in dose is advised. Approximately 30% of cats go into diabetic remission 1 to 4 months after an adequate treatment protocol is instituted.     

Effects and safety of iopanoic acid in cats administered levothyroxine

The purpose of this study was to evaluate the safety and effect of iopanoic acid in 13 cats with hyperthyroidism induced by daily subcutaneous administration of 25microg/kg levothyroxine for a period of 42 days. On day 28 of levothyroxine administration, cats were randomly allocated to receive treatment twice daily with a placebo (control group; n=4), 50mg iopanoic acid (low dose group; n=5), or 100mg iopanoic acid (high dose group; n=4) for 14 days. Compared to the control group, T(3) concentrations were significantly decreased in both the low dose and high dose groups on days 35 and 42. T(3) concentrations in the low dose and high dose groups at days 35 and 42 were not different from day -8. The effect of iopanoic acid on clinical signs of hyperthyroidism was less apparent. Further clinical studies evaluating the long-term effect in cats with spontaneous hyperthyroidism are warranted.     

Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases

This retrospective study describes the clinical progression of 12 cats with pituitary tumours treated with a coarse fractionated radiation protocol delivering a total dose of 37 Gy in five once weekly fractions. A pituitary macrotumour was identified in all 12 cats: 4 with neurological signs only and 8 with insulin‐resistant diabetes mellitus secondary to acromegaly. One of the cats with central neurological signs died before completing the radiotherapy course; the remaining three had partial or complete remissions of their central neurological signs. Of the cats with unstable diabetes mellitus, five no longer required insulin therapy, one required less insulin and two became stable. The overall median survival time was 72.6 weeks; four cats died from related causes, two from unrelated problems and six remain alive. Radiation therapy is confirmed as an effective treatment for feline pituitary tumours, giving prolonged survival and control of both paraneoplastic and mass effect signs.     

Plasma alpha-tocopherol profiles in sheep after oral administration of dl-alpha-tocopheryl acetate and d-alpha-tocopheryl polyethylene glycol-1000 succinate.

Twenty-five yearling wethers, weighing 45 to 50 kg, were used in a trial designed to compare the bioavailability of dl-alpha-tocopheryl acetate (TA) and d-alpha-tocopheryl polyethylene glycol-1000 succinate (TPGS). The sheep, five per treatment, were each given a basal diet without vitamin E supplement (control) or with a daily oral supplement of 240 iu TA or TPGS, or of 480 iu TA or TPGS. Blood samples were obtained at zero time, and then twice daily for three weeks. The bioavailability was greater for TA than for TPGS. This was indicated by the significantly higher (P less than 0.01) plasma alpha-tocopherol concentrations during the three-week experimental period in sheep dosed with equivalent units of TA than in those dosed with TPGS. When administered at 480 iu, the TPGS produced plasma profiles similar to those found after administration of the lower (240 iu) dose of the TA.     

Metronidazole for the treatment of feline giardiasis

There are several drugs available for the treatment of giardiasis in cats, including metronidazole. The purpose of this study was to determine whether metronidazole benzoate administered at a dose of 25 mg/kg, orally, twice a day for 7 days lessens or eliminates Giardia cyst shedding in cats with chronic infection. Twenty-six, adult, laboratory-reared cats were used in this study. Sixteen cats had been inoculated orally with cysts of a human Giardia sp. isolate and had completed a Giardia vaccine study in one animal holding room. The other ten cats were infected with the same Giardia sp. presumably by contamination from the adjacent room where the Giardia vaccine study cats were located. From each cat, a fecal sample was collected within 1 week of the start of treatment and then every 2 to 4 days for 15 days after treatment was completed. Fecal samples were analyzed for the presence of Giardia cysts using a commercially available direct immunofluorescence test (IFA). Clinical signs of drug toxicity were not detected during the study.     

Exenatide dosing in alpacas

In order to investigate whether exenatide could be used to stimulate glucose clearance and insulin secretion in alpacas without causing colic signs, six healthy adult alpacas were injected once a day with increasing subcutaneous doses. A follow‐up intravenous glucose injection was given to induce hyperglycemia, and serial blood samples were collected to measure plasma concentrations of glucose, insulin, triglycerides, beta‐hydroxybutyrate, and nonesterified fatty acids. The exenatide doses used were saline control (no drug), and 0.02, 0.05, or 0.1 mcg/kg injected subcutaneously. Alpacas had significantly lower plasma glucose concentrations and higher insulin concentrations on all treatment days compared with the control day, but the increase in insulin was significantly greater and lasted significantly longer when the alpacas received the two higher dosages. Two of the alpacas developed mild colic signs at the 0.05 mcg/kg dose and were not evaluated at the highest dose. Based on these findings, the 0.05 mcg/kg dose appears to offer the greatest stimulation of insulin secretion and glucose clearance without excessive risk or severity of complications.     

Pharmacokinetics of tinidazole in dogs and cats

Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study. Tinidazole was completely absorbed at both oral dose levels in cats and dogs. Peak tinidazole concentration in plasma was 17.8 micrograms/ml in dogs and 22.5 micrograms/ml in cats after 15 mg/kg p.o. The oral dose of 30 mg/kg resulted in peak levels of 37.9 micrograms/ml in dogs and 33.6 micrograms/ml in cats. The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half-life that was twice as long in cats (8.4 h) as in dogs (4.4 h). The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats. Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole-sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg. From the pharmacokinetic standpoint tinidazole seems to be well-suited to clinical use in small animal practice.     

Use of low carbohydrate, high protein diets in cats with diabetes mellitus

The goal of this randomized, double‐blind study was to compare the effects of feeding a low carbohydrate, high protein diet versus a maintenance diet in a group of cats with diabetes mellitus treated with insulin glargine twice daily. All cats with naturally occurring diabetes mellitus not currently treated with insulin glargine or diabetogenic drugs or being fed a low carbohydrate, high protein diet were eligible for inclusion. Baseline testing included a physical examination, complete blood count, serum biochemistry profile, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were treated with insulin glargine (starting dose of 0.25 U/kg) twice daily. Insulin was adjusted as needed for glucose regulation. Cats were randomized to receive either a low carbohydrate, high protein diet or a feline maintenance diet. Re‐evaluations were performed on all cats at weeks 1, 2, 4, 6 and 10, and included an assessment of clinical signs, physical examination, 12‐h blood glucose curve, and serum fructosamine concentrations. Changes in continuous variables over the course of the study were analyzed using analysis of variance with repeated measures. p < 0.05 was considered statistically significant. Ten cats have completed the study. There were no significant differences between diet groups at baseline for age, gender, weight, body condition score, serum glucose or fructosamine concentrations. Although there was not a significant difference over time in clinical signs, insulin doses, or peak or nadir glucose concentrations between diet groups, diet did have a significant effect on serum fructosamine concentrations (p = 0.01). Six of the 10 cats that have completed the study achieved complete remission by the end of the study period, with no statistical difference between diets. The study's results indicate that diet can have significant effects on glucose regulation in cats receiving insulin glargine for treatment of feline diabetes mellitus.     

Comparison of regular insulin infusion doses in critically ill diabetic cats: 29 cases (1999–2007)

Objective – To compare biochemical parameters, neurologic changes, length of hospital stay, and clinical improvement in 3 groups of cats with diabetic ketosis/diabetic ketoacidosis (DK/DKA) prescribed varied doses of regular insulin as a continuous rate of infusion (CRI). Design – Retrospective study. Setting – University teaching hospital. Animals – Twenty‐nine client‐owned cats with DK/DKA prescribed a regular insulin CRI. Interventions – Cats were grouped as follows: 7 cats each in Group 1 and 2, (prescribed 1.1 and 2.2 U/kg/d, respectively), and 15 cats in Group 3 (prescribed increasing doses as needed). Measurements and Main Results – None of the groups received the total prescribed dose of insulin. The mean actual dose administered/kg/d ranged from 0.30 (0.21) to 0.87 (0.32) U/kg/d in Groups 1, 2, and 3. There was no difference in mean minimum blood glucose (BG) per 4 hours or change in BG from baseline per 4 hours between Groups 1 and 2 (P=0.63, 0.50). There was no difference between groups regarding the time required to reach a BG ≤13.9 mmol/L (250 mg/dL), serum phosphorus or potassium concentrations relative to baseline values (P=0.53, 0.90), length of time until urine or serum ketones were no longer detected (P=0.73), the animal commenced eating (P=0.24), or length of hospital stay (P=0.63). Four of the cats had declining mentation during hospitalization; there were no relationships between osmolality at presentation, either prescribed or administered insulin dose, and mentation changes. Three of the 4 cats with declining mentation survived. Twenty‐seven of the 29 cats (93%) survived to discharge. Conclusions – In this study, prescribing the published canine dose (2.2 U/kg/d) of regular insulin to cats with DK/DKA does not appear to increase the frequency of adverse neurologic or biochemical sequelae compared with cats that are prescribed the published cat dose (1.1 U/kg/d). The use of a sliding scale for determination of infusion rates significantly reduces the amount of insulin cats receive in this setting. Determination of whether adverse sequelae would occur more frequently if cats with DK/DKA received the full insulin prescribed doses of 1.1, 2.2, or >2.2 U/kg/d is warranted. Further controlled studies are necessary to determine if higher doses of insulin are associated with beneficial effects on morbidity or mortality.     

Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats

Objective To evaluate the efficacy and tolerance of a treatment protocol for anxiety-related and obsessive-compulsive disorders in cats.
Design A study was undertaken to assess the clinical response in cats diagnosed with anxiety-related or obsessive-compulsive disorders to a treatment regimen that included clomipramine and behaviour modification.
Procedure The study group of 11 cats was acquired through referral. A detailed behavioural and clinical history was obtained. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalisation in one. Clomipramine was administered orally once daily. The mean starting dose was 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. A behaviour modification program was designed and the owner instructed on its implementation. Cats were to continue on medication for at least 1 month after clinical signs disappeared, then medication withdrawal was to be attempted by decreasing the clomipramine dose progressively at weekly intervals while the behaviour modification program continued.
Results In all cases the presenting clinical sign was largely improved or disappeared. One cat was removed from the study by the owner. Four cats became lethargic at higher doses, but this resolved when the clomipramine dose was reduced. The average maintenance dosage was 0.3 mg/kg once daily. Clomipramine withdrawal was attempted in two cases: the behaviour returned in one case and the medication was reinstated at 0.3 mg/kg twice daily.
Conclusion Clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behaviour modification. Clomipramine was well tolerated.     

Effects of diet on glucose control in cats with diabetes mellitus treated with twice daily insulin glargine

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.     

Concurrent diabetes mellitus and hypoadrenocorticism in the dog: Diagnosis and management of eight cases

Eight cases of concurrent diabetes mellitus and hyperadrenocorticism are described. In all but one dog diabetes mellitus was the first condition recognised and, in these, clinical signs attributable to hyperadrenocorticism developed further while the dogs received replacement insulin therapy. The most common signs were resistance to exogenous insulin with daily insulin replacement dosage requirements exceeding 2 iu/kg, erratic insulin requirements, continuing polydipsia/polyuria and weight loss. Lethargy and muscle weakness were variable and dermatological abnormalities were present in only four cases. Six dogs were treated with op'DDD and clinical signs resolved with improvement of glycaemic control.     

The safety of high‐dose buprenorphine administered subcutaneously in cats

The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol‐specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine‐treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug‐related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats.     

Metronidazole neurotoxicosis in two cats

Two cats were presented for neurological dysfunction from suspected metronidazole toxicity. One cat was receiving 111 mg/kg body weight per day of metronidazole for 9 weeks. After 9 weeks, the dose was increased to 222 mg/kg body weight per day, and 2 days later the cat began to experience progressive neurological signs that culminated in generalized seizures. The second cat was receiving metronidazole at a total dose of 58 mg/kg body weight per day for 6 months. This cat experienced acute onset of ataxia and alteration in mentation. Laboratory evaluations in both cases were without significant findings. The neurological signs in both cats resolved within days of initiating supportive therapy and withdrawal of the drug. This report describes the two cases and discusses the etiology of metronidazole neurotoxicosis.     

Comparison of the Polymerase Chain Reaction and Culture for the Detection of Feline Chlamydia psittaci in Untreated and Doxycycline-Treated Experimentally Infected Cats

The diagnostic sensitivity of the polymerase chain reaction (PCR) was compared with that of culture on conjunctival swabs over the course of infection in 4 doxycycline-treated and 4 untreated cats that were experimentally infected with feline Chlamydia psittaci. Treated cats were given 25 mg (5 mg/kg) of doxycycline orally twice daily for 3 weeks from day 6 after challenge. Clinical signs improved within 3 days of institution of treatment. Culture remained positive for 1 day and PCR remained positive for up to 5 days after treatment was commenced. No recurrence of clinical signs occurred and the organism could not be detected by either PCR or culture for 2 weeks after cessation of therapy. In the 4 untreated cats, conjunctival swabs were taken daily to day 14 and every 2nd weekday to day 64 after challenge. PCR was significantly more sensitive than culture in untreated cats overall (PCR 85.7%, culture 72.9%, P approximately 0) and for cats with clinical signs (PCR 89.2%, culture 79.2%, P = .008). PCR and culture had equivalent sensitivity (100%) for cats showing clinical signs in the 1st month of infection, whereas PCR was considerably more sensitive than culture for cats showing clinical signs in the 2nd month (PCR 72.9%, culture 47.9%, P = .028). Organisms were not detected by PCR in blood or any tissue collected from treated or untreated cats at postmortem. Thus, effective treatment of chlamydiosis in cats is possible with much shorter treatment regimens than currently recommended, and PCR is the more sensitive diagnostic method in chronically infected cats.     

Transdermal carbimazole for the treatment of feline hyperthyroidism

Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.     

Coarse Fractionated Radiation Therapy for Pituitary Tumours in Cats: A Retrospective Study of 10 Cases

Introduction:  Pituitary tumours are uncommon in cats. Signs may be due to either an expansile mass or paraneoplastic effects (acromegaly and/or unstable diabetes mellitus). There are a few small case series providing evidence of efficacy for radiotherapy of pituitary tumours in cats. This retrospective study describes the outcome of ten cats with pituitary tumours treated with course‐fractionated radiation.
Methods:  The medical records of cats with MRI‐confirmed pituitary tumours that underwent radiotherapy were reviewed. A standard coarse‐fractioned radiation protocol was used; 37 Gy in 5 once‐weekly fractions using two parallel‐opposed 4MeV X‐ray beams. Survival times were calculated from date of first radiation dose.
Results:  Ten cats with pituitary tumours underwent radiotherapy. 5 cats had CNS signs and 5 had evidence of growth hormone excess (1 cat also showed CNS signs). 2 cats with pre‐existing moderate to severe CNS signs died of unknown causes before completing the radiation course. Of the remaining 4 with CNS signs, 3 had complete resolution of signs and the fourth showed partial improvement. Of the 5 cats with unstable diabetes, 2 no longer required insulin and 3 became stable at a lowered dose. The median survival time was 77.6 weeks. 6 cats died: 2 without completing the radiation course, 2 from unrelated causes (CRF, VAFS) and 2 from relapse and/or progression of CNS signs. 4 cats remain alive (range 34–191 weeks).
Conclusions:  Radiation therapy is confirmed as an effective treatment for pituitary tumours in cats giving extended survival and control of both direct mass effect and paraneoplastic signs.     

Chloramphenicol toxicosis in cats

Six cats were given chloramphenicol orally at the dose level of 120/mg/kg/day in 3 divided doses for 14 days and were then observed for another 3 weeks after treatment. Five other cats were used as untreated controls for the first 14 days and subsequently were given 60 mg of chloramphenicol/kg/day for 21 days. Clinical signs of toxicosis, which were more severe in cats given the higher dose level, included central nervous system depression, dehydration, reduced food intake, body weight loss, sporadic diarrhea, and vomiting. In cats given the higher dose level, chloramphenicol caused reversible marrow suppression, with marrow hypoplasia, maturation arrest of erythroid cells, and inhibition of mitotic activity, and caused vacuolation of lymphocytes and of early myeloid and erythroid cells. Significant changes were evident in bone marrow after treatment for 1 week and in peripheral blood at the end of the 2nd week. Hematologic changes included decreased numbers of neutrophils, lymphocytes, reticulocytes, and platelets. In cats given the lower dose level, changes in blood and bone marrow were similar but less severe.