Internal Medicine @ Feline Focus
Alice M. Wolf, DVM, DACVIM, ABVP (Feline Practice)
Department of Small Animal Med/Surg, Texas A&M; University
Practical Stuff From ACVIM © 2004
Comparison of the Pharmacokinetics and Pharmacodynamics of Glargine, Protamine Zinc, and Porcine Lente Insulins in Normal Cats. - RD Marshall, et al. U Queensland, Australia
Because of the difficulties in insulin administration and regulation in some diabetic cats, there is considerable interest in glargine (Lantus®- Aventis) insulin. Glargine is marketed as "peakless" insulin and is given once daily in humans. This study was undertaken as a preliminary evaluation of glargine insulin in normal cats. Subjects were 9, healthy, neutered adult cats, 5 male, 4 female. Insulin of each type was administered as a single SQ injection at a dose of 0.5 U/kg. Blood glucose and insulin measurements were performed hourly for 24 hours post-injection. 3 days elapsed between each trial. There was no significant difference in time to onset among the 3 insulins. Time to reach glucose nadir was longer for glargine (16± 1.9 hours) than for PZI (6±2.3) or Lente (4±0.5). The glucose nadir was not significantly different among the insulins. Time for glucose to return to baseline was significantly shorter for Lente than for PZI or glargine. Conclusions: Glargine insulin produces a later glucose nadir than PZI or Lente and has a longer duration of activity than Lente. Apparently, unlike humans, in cats there are definite peaks of insulin activity comparable to other insulin types.
Comparison of the Pharmacokinetics and Pharmacydynamics of Once versus Twice Daily Administration of Insulin Glargine in Normal Cats. - RD Marshall, et al. U Queensland, Australia
This study performed by the same authors as above used 6 cats (3 each male and female). Glargine insulin was given at 0.5 U/kg SQ q24h or 0.25 U/kg SQ q12h. Conclusions: Both regimens produced a significant blood glucose lowering effect. The duration of glucose suppression was much longer with q12h dosing. In 33% of cats treated q12h, blood glucose concentrations were still suppressed at 24 hours which might produce a "piggybacking" effect during long term therapy. Further study is needed to determine the utility of glargine insulin in cats with naturally-occurring diabetes mellitus. Ed. Note: Information from the product literature indicates that glargine may produce more pain at the site of injection. It is available as 100 U/ml strength in 5 and 10 ml vials. If refrigerated, glargine should be used within 28 days of opening.
Parenteral Administration of FVRCP Vaccines Induces Antibodies Against Feline Renal Tissues. - MR Lappin, CSU
CRF often associated with lymphoplasmacytic interstitial nephritis (suggestive of immune-mediated disease) is a common cause of morbidity and mortality in older cats. Viruses used in feline FVRCP vaccines are commonly grown in Crandall-Reese Feline Kidney (CRFK) cells. Vaccines produced from these viral cultures will contain CRFK antigens. This study was undertaken to determine whether CRFK antigens in vaccines would stimulate antibody against feline renal tissue. 14 unvaccinated kittens were divided into 7 pairs. Treatments included: 10 µg CRFK protein SQ, 50 µg CRFK protein SQ, 50 µg CRFK protein + aluminum adjuvant SQ, IN feline FVRCP, or one of 3 commercial FVRCP vaccines SQ. The concentrations of CRFK proteins was comparable to those determined to be present in vaccines. CRFK proteins were given every 2-4 weeks for a total of 8 injections. FVRCP vaccines were given every 3 weeks for a total of 3 inoculations (typical vaccination series). Serum samples were collected prior to treatment and 6 months later. None of the cats was positive for antibody against CRFK or feline renal tissue (FRT) prior to inoculation. Six months post-inoculation, 6/6 kittens inoculated with CRFK had anti-CRFK antibody, 5/6 also had anti-FRT antibody. 5/6 vaccinated kittens had anti-CRFK antibody, 4/6 had anti-CRFK antibody. Neither of the IN vaccinated kittens had anti-CRFK or anti-FRT antibody. Conclusion: Administration of parenteral FVRCP vaccines SQ can induce anti-FRT antibodies which may play a role in the development of chronic progressive renal disease later in life. Further study is needed but this may be yet another reason to limit vaccination to what is absolutely necessary in cats.
Feline antibody response to Fort Dodge Fel-O-Vax FIV vaccine interferes with FIV diagnostic tests. - R Groat, et al: IDEXX Diagnostics
Subjects were 4 cats vaccinated with Fel-O-Vax FIV vaccine according to label directions. Blood samples were collected for assessment of the presence of anti-FIV antibody (positive "FIV test") prior to vaccination, at 28 days, 4, 7, and 13 months after completing the vaccination series. Samples were tested with the IDEXX Snap-Combo (FeLV and FIV), PetCheck FIV, and Western blot. All pre-vaccination samples were negative for anti-FIV antibody. All samples taken from 28 days to 13 months post vaccination were strongly positive for FIV antibody. Conclusions: It is impossible to distinguish antibody generated by FD FIV vaccine from AB generated by naturally-acquired FIV infection on the basis of presently available tests for at least 13 months.
Infectious organisms in feline chronic rhinosinusitis. Correlation of rhinoscopic findings with nasal biopsy in cats. LR Johnson, et al: U.C. Davis
Subjects included 10 cats with chronic Mucopurulent nasal discharge with a duration of signs from 3-24 months. The control group consisted of 5 apparently normal cats without respiratory tract signs. Rhinoscopy, unilateral diagnostic nasal flush, and bilateral biopsy was performed on all cats. Samples were submitted for aerobic, anaerobic, mycoplasma cultures, histopathology, PCR for Herpesvirus, virus isolation for other viruses. Three of 5 asymptomatic cats were found to have aerobic bacteria present on culture. In the "snuffler" cats, aerobic bacteria were cultured in 9/10, anaerobic bacteria in 3/10, Mycoplasma in 2/10. FHV was not cultured from any cat. PCR for herpesvirus was positive in 3/10 (30%) of the snuffler cats and 3/5 (60%) of the normal asymptomatic cats. This indicates that herpesvirus is not an active participant in the chronic snuffler complex and that while detectable it does not appear to be viable on culture.
Forty-five cats were evaluated with rhinoscopy and biopsy. Biopsy specimens were scored on the gross appearance and on the severity of histologic lesions. The results demonstrated that samples with minimal histologic change usually had low gross appearance scores. Samples with moderate to severe inflammation also often had low gross scores. The gross appearance of the nasal mucosa as assessed during rhinoscopy is often misleading with respect to the actual severity of the disease seen on histopathology. Therefore, ALWAYS take biopsies as part of your nasal cavity diagnostic testing.
Clinical efficacy of transdermal methimazole in cats with hyperthyroidism. - LL Sartor et al. University of Wisconsin
Subjects were 44 cats with newly diagnosed feline hyperthyroidism. Both transdermal (27 cats) and oral (17 cats) treatment groups received a methimazole dose of 2.5 mg q12h. Evaluation of the cat by body weight, physical examination, CBC, biochemistry profile, UA, total T4, blood pressure and owner evaluation was performed pre-treatment (day 0), and 2, and 4 weeks into the treatment regimen. There were no significant differences in laboratory or physical assessments between groups prior to treatment. At 2 weeks, 86% of the orally treated group was euthyroid compared to 56% of the topical group. At 4 weeks the results were 82% and 67% respectively. There was not a significant difference between groups. Gastrointestinal side-effects were seen in 23.5% of the group treated with oral methimazole but only 3.7% of the cats treated with transdermal drug. There was no difference in the occurrence of leucopenia, hepatotoxicity, or facial excoriations between the groups. The conclusions to the study were that transdermal methimazole is effective, requires slightly longer induction time to reach euthyroid status, and is associated with fewer GI side-effect compared to orally administered drug. Topical methimazole is a viable treatment option.
Prevalence and risk of Tritrichomonas foetus in cattery cats. - JL Gookin, et al, NCSU.
A study of 119 cats in 89 catteries was performed. The prevalence of T. foetus was 31% for all cats and 31% of catteries. The prevalence of Giardia sp was 31% for cats and 35% for catteries. Co-infection with both T. foetus and Giardia was present in 12% of cats and 16% of catteries.
Outcome of cats with diarrhea and Tritrichomonas foetus. - DM Foster et al: NCSU
Subjects were 26 cats with large bowel diarrhea and confirmed TF infection. 22/26 cats had abnormal stools daily, 3/22 weekly and 1/22 monthly. Signs had been present for a median of 2.5 months (range: 0-24 mos). Clinical signs resolved in 23 cats, 4-24 months after the onset of diarrhea (median 9 months). Recurrent bouts of diarrhea were seen in 12/25 cats after initial improvement or resolution. Organisms were still detectable (fecal culture, PCR) in 60% of cats despite apparent resolution of clinical signs. Conclusions: Cats may experience spontaneous resolution of T. foetus associated diarrhea within 2 years of diagnosis. Infrequent recurrences of diarrhea may be triggered by diet change, stress, or medication.
Enrofloxacin for Treatment of Cats Experimentally Infected with Large Form Haemobartonella felis. - KL Dowers, et al. CSU
Haemobartonella has recently been reclassified as a Mycoplasma. The large (pathogenic) variant now carries the name Mycoplasma haemofelis (Hflg). 16 cats were experimentally infected with Hflg and divided into 4 treatment groups: Doxycycline 5 mg/kg PO q12h, Enrofloxacin 5 mg/kg PO q24h, Enrofloxacin 10 mg/kg PO q24h, and an untreated control group. Clinical signs, PCV, blood smears, and PCR were used to monitor the cats. Cats PCR negative at 8 weeks were given methylprednisolone (20 mg/kg IM weekly) for 3 weeks and were evaluated weekly, then 6 months later for recurrence. All cats were positive for Hflg by PCR and blood smears following infection. During treatment, organism counts for the doxycycline treated group and 10 mg/kg Enro group decreased faster than those in the control group. Treatment had no effect on the PCV during the treatment period, however PCVs were higher in the Enro5 group compared to the control group after treatment. There was no significant effect of any treatment on the number of PCR positive results (cats still infected). 3 cats (1 doxy, 2 Enro 10) were persistently PCR negative even following methylprednisolone challenge. Conclusions: Enrofloxacin was as effective as doxycycline in the treatment haemobartonellosis in cats. Ed Note: The 10 mg/kg dose is higher than recommended and concern for ocular effects may limit its use at this dosage. Trials with other quinolones have not yet been performed.
Imidocarb diproprionate for the treatment of recurrent haemobartonellosis in cats - MR Lappin, CSU.
Subjects were 5 cats with treatment resistant haemobartonellosis. Two cats were infected with the large form: M. haemofelis, two with the small form: M. haemominutum, and one was not identified (cytologic diagnosis only). Previous failed treatments had included doxycycline and prednisone (2 cats), Doxy, Enro, and pred (1 cat), Doxy, Tetra, Enro, and Pred (1 cat), and Doxy, Enro, Chloro, Pred in one cat. Imidocarb was used as a sole agent or added to the failing protocol at a dose of 5 mg/kg IM. This treatment was repeated in 14 days as needed. One cat responsed to a single dose of imidocarb, one responded to 2 doses and both are normal after 9-14 months. Two cats required 4 doses (at 2 week intervals) both were normal after 3-7 months. One cat requires monthly imidocarb injections to maintain a normal PCV (after 14 months). Conclusions: Imidocarb diproprionate is useful for the treatment of resistant hemobartonellosis in cats. Ed note: This drug is not approved for cats. Pre-treat with atropine IM, 30 minutes prior to drug administration.
Infectious Causes of Fever in Cats. - MR Lappin, et al. CSU
Serum samples were collected from 121 cats with fever. These were matched with 99 geographically matched cats without fever. Cat sera were evaluated for FeLV, FIV, FCoV (coronavirus), T. gondii, E. canis, E. equi, Haemobartonellosis (M. hemofelis, M. hemominutum), B. heneslae, B. clarridgeiae, Ehrlichia species (PCR). Results showed evidence of exposure to one or more infectious agent in 54% of cats with fever and 50% of cats without fever. Conclusions: Since each of the assays can be positive in cats with and without fever, causation of fever cannot be proven on the basis of a test result alone.
Treatment of Feline Leukemia Virus Infection with 3-azido-2,3-diedeozythymidine (AZT) and Human Alpha-Interferon (huIFN). - K Hartmann, et al. U Zurich, Switzerland
Subjects consisted of 44 cats naturally-infected with FeLV. These were randomly assigned to one of 4 treatment groups. Cats were treated for a period of 6 weeks with: AZT (5 mg/kg PO q12h), huIFN (100,000 IU/kg SQ q24h), AZT and huIFN, or placebo. Evaluation included clinical, laboratory, virological, and immunologic assessment. Evaluators were blinded regarding treatments cats were receiving. None of the cats became FeLV antigen negative during the treatment period. A trend toward general clinical improvement and improvement in some specific signs (e.g. stomatitis) occurred in treated cats, however, the improvement was not statistically significant. CD4+ and CD8+ cell counts did not change significantly. No synergy between drugs was observed. Most patients did not show side effects of treatment, however, on cats was withdrawn from the AZT group due to severe anemia developing on the 3rd week of treatment. Conclusions: Treatment with AZT and/or huIFN (SQ) did not produce significant improvement in clinical signs, laboratory findings, viral load, or immunologic parameters. A longer treatment period might produce better results, however, cats quickly (7-8 weeks) develop antibodies to huIFN given SQ and a longer treatment period with this agent may not be possible.
Relation of survival time and urinary protein excretion on cats with renal failure and/or hypertension. - HM Syme - RVC, London UK
The objective of this study was to investigate the relationship of proteinuria to survival time in cats with variable renal function and with or without systemic hypertension. The subjects were normal cats (USG > 1.035, normal chemistry), cats with PCRD (USG < 1.035, Cr > 1.9) and cats with hypertension (consistently > 175 mmHg). Outcome: Median survival time of cats with UPC > 0.43 = 281 days, survival of cats with UPC < 0.43 = 766 days. Conclusions: proteinuria predicts reduced survival time in cats with CPRD. Further studies with interventions that decrease proteinuria are warranted to see whether this strategy increases survival times.
Influence of proteinuria on survival time in cats with chronic renal insufficiency. - D Gunn-Moore, Edinburgh
Subjects of the study were 193 cats with chronic progressive renal disease. Subjects were divided into two treatment groups: control (placebo) and treatment with benazapril HCl 0.5 - 1.0 mg/kg PO q24h. Cats were followed for up to 3 years and assessed for progression of their renal disease. The mean survival time for the control group was 520 days compared to 637 days for the benazapril treatment group. This difference overall was not statistically significant. However, for the subgroup of cats with proteinuria (UPC > 1.0), benazapril significantly increased survival time. Therefore it may be useful for this subgroup of cats with proteinuric CPRD.
Efficacy of Giardia vaccination for treatment of giardiasis in cats. - JE Stein, CSU
Subjects were 16 young adult cats, male and female, negative for FeLV/FIV/Giardia. Cats were individually housed and infected with a human-derived Giardia strain. All cats became positive and shed oocysts but had minimal clinical signs. Eight of the cats were selected randomly and vaccinated at 4, 6, and 10 weeks post-infection with Fel-O-Vax Giardia vaccine. Three fecal samples were collected weekly for 28 weeks post-infection. At 28 weeks, 5/8 vaccinated cats and 7/8 control cats were still shedding oocysts. There was a general trend towards decreased oocyst shedding in all cats over time. The investigators concluded that Giardia vaccine was not effective in eliminating oocyst shedding in this model. There were minimal clinical signs in both treated and untreated cats. The efficacy of the Giardia vaccine as a treatment in naturally-infected cats remains to be determined.
Unusual Manifestations of Cancer in Cats© 2004
There are a number of recently recognized vascular and metabolic metastatic manifestations of pulmonary neoplasia in cats. These include the lung-digit syndrome (metastatic digital carcinoma), neuromuscular weakness, hypercalcemia of malignancy, arterial thromboembolism (ATE), and posterior ocular segment metastasis. Several of these syndromes may occur in the same animal. Vascular complications may occur due to direct invasion by the tumor, thrombocytosis secondary to neoplasia, metastatic showering to distant locations, and coagulopathy associated with neoplasia. This presentation will use case studies to illustrate some of the syndromes so that they will be come more recognizable for the practitioner.
The presentation for these patients with ATE secondary to pulmonary neoplasia is identical to that of cats with ATE associated with cardiac disease. Clinical signs include acute paresis of limbs or muscular pain. Limbs are cool to the touch, pulses are weak to the affected limbs, and gross lesions of infarction may be evident in the distal extremities. Nail beds and paw pads are often purple and bleeding is sluggish or absent when a claw is trimmed to the quick. Extreme pain due to muscle anoxia is often present. Pulmonary radiographs taken at the time of the initial thromboembolic event may or may not demonstrate an obvious pulmonary mass. Disseminated pulmonary neoplasia may be very diffuse and below the level of detection of plain film radiographs. Diagnostic evaluation is directed to confirming the diagnosis of ATE and ruling out cardiac causes for this event. Laboratory evaluation often reveals leukocytosis and markedly elevated CPK and AST levels. Renal function may be compromised if the thrombus involves the renal arteries. Treatment is directed at pain control and supportive care to assist restoration of arterial blood flow. The prognosis for ATE overall is poor and these patients have the additional problem of pulmonary neoplasia that will worsen over time.
METASTATIC DIGITAL CARCINOMA
Pulmonary neoplasms in the cat may have an unusual metastatic distribution pattern involving the terminal phalanx of the digits. One or more digits of the same or different limbs may be affected. The affected digits are swollen, warm, painful, and may have evidence of exudation at the nail bed or sloughing of the nail. Topical (e.g. soaks or ointments) and systemic therapies (e.g. antibiotics or corticosteroids) do not resolve the problem. Radiographs of the affected digit reveal lysis of the bone of the third phalanx that does not involve or cross the joint space. Radiographs of the thorax will reveal various patterns of pulmonary neoplasia. The affected digit(s) may be excised to help resolve pain, however, the primary pulmonary problem still exists and recurrence in other digits is possible. In addition, depending on the type and aggressive nature of the pulmonary lesion, signs of lung dysfunction (dyspnea, etc) may appear soon.
POSTERIOR OCULAR SEGMENT METASTASIS
Intraocular metastasis of feline bronchiogenic carcinoma causes an ischemic chorioretinopathy. Clinical signs may or may not be related to the eye. A thorough ophthalmoscopic evaluation should be performed in all cats with suspect pulmonary neoplasia in order to detect these lesions. No specific treatment for the ocular lesions is indicated unless pain is severe. The prognosis is poor because of the primary pulmonary involvement.
Vasoinvasive pulmonary carcinomas may metastasize to the muscle or neurologic tissue and produce weakness associated with either primary neurologic damage or polymyopathy. Muscular involvement may result in pain on deep palpation. Neurologic lesions may produce a diffuse array of deficits depending on the distribution of the metastases. Although this is an unusual manifestation of pulmonary neoplasia, thoracic radiography to evaluate for this problem, should be recommended in cats with poorly defined neuromuscular weakness or neurologic signs.
HYPERCALCEMIA OF MALIGNANCY
Pulmonary neoplasms may occasionally be associated with pseudohyperparathyroidism in cats. The clinical signs relating to this condition may or may not be present. Renal failure is the most common sequel to prolonged hypercalcemia. Because hypercalcemia is often associated with malignancy, thoracic radiographs are indicated in a search for occult neoplastic lesions. The prognosis for affected cats is very poor because of the effects of hypercalcemia as well as the presence of primary pulmonary neoplasia.
This presentation will use case studies to demonstrate some of these various syndromes.
Zen and the Art of Cat Maintenance I & II © 2004
There is as much "art" as science in the practice of veterinary medicine generally, and in feline practice in particular. The following are some useful (I hope) thoughts gleaned from practical veterinary practice related to the feline species.