Procedure—Mitogen-stimulated lymphocyte proliferation
in whole blood incubated with and without various
concentrations of cyclosporine, tacrolimus,
sirolimus, mycophenolic acid (MPA), or A771726 was
measured by use of [3H]thymidine incorporation. Drug
concentrations that resulted in a 50% inhibition of
mitogen-induced proliferation (IC50) were calculated.
Lymphocyte viability was determined by use of the trypan blue dye exclusion method.
Results—An obvious dose-response relationship for
the antiproliferative effects of each drug was detected.
Mean IC50 determined with concanavalin A was
46 nMfor cyclosporine, 9 nMfor tacrolimus, 12 nM
for sirolimus, 16 nM for MPA, and 30 mM for
A771726, whereas with pokeweed mitogen, mean
IC50 was 33 nM for cyclosporine, 5 nMfor tacrolimus,
15 nM for sirolimus, 14 nM for mycophenolic acid,
and 25 mM for A771726. Mitogen-stimulated and
nonstimulated lymphocytes remained viable, regardless
of drug evaluated.
Conclusions and Clinical Relevance—Tacrolimus,
sirolimus, MPA, and A771726 inhibited in vitro mitogen-
stimulated proliferation of feline lymphocytes in a
dose-dependent manner. These novel immunosuppressive
drugs may be useful for management of
immune-mediated inflamMatory diseases and prevention
and treatment of rejection in cats that undergo
organ transplantation. (Am J Vet Res 2000;61:
Objective—To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species [ROS]) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils.
Sample Population—Peripheral neutrophils obtained from 8 healthy cats.
Procedure—Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining.
Results—Addition of FTY720-P caused a slight non-significant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils.
Conclusions and Clinical Relevance—FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.
Objective—To determine long-term outcome of cats
treated conservatively or surgically for peritoneopericardial
diaphragmatic hernia (PPDH).
Animals—67 cats with PPDH.
Procedure—Medical records of cats with a diagnosis
of PPDH made from 1987 through 2002 were
reviewed. Information regarding long-term outcome
was obtained from owners.
Results—Prevalences of PPDH in domestic longhair
and Himalayan cats were significantly greater and
prevalence of PPDH in domestic shorthair cats was significantly
lower than prevalence of PPDH in the hospital
cat population over the 15-year study period.
Historical problems most commonly related to the respiratory
and gastrointestinal tracts. Peritoneopericardial
diaphragmatic hernia was the primary diagnosis in 40
cats and an incidental finding in 27 cats. One cat died
prior to arrival at the Veterinary Medical Teaching
Hospital. Thirty-seven of 66 cats were treated surgically,
and 29 were treated conservatively. The postoperative
mortality rate was 14%. Postoperative complications
developed in 29 of 37 cats, the most common of
which was hyperthermia. Two of 22 conservatively
treated cats had progression of clinical signs necessitating
surgical intervention or resulting in death. Owner
satisfaction with treatment choice and long-term outcome
was rated as very satisfied by 88% of owners of
surgically treated cats and 68% of owners of conservatively
Conclusions and Clinical Relevance—Cats with overt
clinical signs attributable to PPDH are good candidates
for surgical herniorrhaphy. Postoperative complications
may develop but are generally minor and self-limiting.
Long-term outcome of cats treated conservatively or
surgically was rated as very good by most owners.
(J Am Vet Med Assoc 2004;224:728–732)
Objective—To document the signalment; history;
clinical signs; clinicopathologic, diagnostic imaging,
and surgical findings; perioperative complications;
and long-term clinical results of ameroid ring constrictor
(ARC) placement on single extrahepatic portosystemic
shunts (PSS) in cats.
Animals—23 cats treated with an ARC on a single
Procedure—An ARC was placed surgically around
the PSS. Portal pressure was measured prior to ARC
placement, with complete temporary PSS occlusion,
and after ARC placement. Cats were scheduled for
recheck transcolonic portal scintigraphy 8 to 10
weeks after surgery. Follow-up information was
obtained by telephone interview with the owners.
Results—An ARC was successfully placed in 22 of
23 cats. Intraoperative complications, consisting of
PSS hemorrhage, occurred in 2 cats. Mean (± SD)
portal pressure (n = 15) was 6.7 ± 2.9 mm Hg before
PSS manipulation, 18.6 ± 7.7 mm Hg with complete
temporary PSS occlusion, and 6.9 ± 2.7 mm Hg after
ARC placement. Postoperative complications developed
in 77% (17 of 22) of cats after ARC placement,
and included central blindness, hyperthermia, frantic
behavior, and generalized motor seizures.
Perioperative mortality rate was 4.3% (1 of 23).
Persistent shunting was identified in 8 of 14 cats.
Overall, 75% (15 of 20) of cats had an excellent longterm
Conclusions and Clinical Relevance—Placement of
an ARC on single extrahepatic PSS in cats resulted in
low surgical complication and perioperative mortality
rates, but most cats did have substantial postoperative
complications. Persistent shunting was common,
although many cats with persistent shunting were
clinically normal. (J Am Vet Med Assoc 2002;220: 1341–1347)
Objective—To determine outcome of renal transplantation in cats with renal failure associated with calcium oxalate urolithiasis.
Design—Retrospective case series.
Procedure—Medical records were reviewed for evaluation of signalment, preoperative clinical signs, physical examination results, dietary history, clinicopathologic data, abdominal imaging, postoperative diet, complications, and long-term outcome.
Results—The domestic shorthair was the most common breed represented. There were 13 spayed females and 7 castrated males. Mean age was 6.8 years. Clinical signs included weight loss, lethargy, vomiting, anorexia, polyuria, and polydipsia. Before surgery, cats received commercially available canned or dry food (n = 10), a prescription renal failure diet (5), a commercial diet to manage struvite crystalluria (1), or an unknown diet (3). Seventeen cats were anemic. All cats were azotemic. Hypercalcemia was detected in 7 cats. Abdominal imaging revealed nephrolithiasis, ureterolithiasis, or both in all cats. Median duration of survival of all cats was 605 days. Eight cats were alive 282 to 2,005 days (median, 1,305 days) after surgery. Eleven cats died 2 to 1,197 days (median, 300 days) after surgery. Five cats formed calculi in their allograft (120 to 665 days). Two of the 5 cats that formed calculi were hypercalcemic. Four of the 5 cats died following complications associated with formation of calculi.
Conclusions and Clinical Relevance—Renal transplantation appears to be a viable option for cats in renal failure secondary to calcium oxalate urolithiasis. In addition to reported complications in renal transplant recipients, formation of calculi within the allograft may also occur.
Objective—To evaluate long-term clinical outcome in dogs with upper airway obstruction treated with laryngeal web resection and mucosal apposition.
Design—Retrospective case series.
Animals—15 client-owned dogs with laryngeal web formation.
Procedures—Medical records of dogs with laryngeal webs treated with a single procedure of web resection with mucosal apposition by use of a ventral laryngotomy were reviewed. Signalment, history, clinical signs, intraoperative complications, postoperative complications, and hospitalization time were recorded. Owners were interviewed 6 months to 6 years after surgery.
Results—Most dogs had a history of oral ventriculocordectomy. Duration of clinical signs ranged from 3 months to 3 years. The most common clinical sign reported was exercise intolerance. Postoperative complications were observed in 4 dogs. Follow-up information was available in 10 dogs, and clinical outcome was classified as excellent in 7 and good in 3.
Conclusions and Clinical Relevance—A single surgical procedure of web resection with mucosal apposition for the treatment of laryngeal web formation in dogs resulted in low morbidity and was associated with a good to excellent outcome.
Objective—To describe pharmacokinetics of multidose
oral administration of tacrolimus in healthy cats
and evaluate the efficacy of tacrolimus in the prevention
of allograft rejection in cats with renal transplants.
Animals—6 healthy research cats.
Procedure—Cats received tacrolimus (0.375 mg/kg,
PO, q 12 h) for 14 days. Blood tacrolimus concentrations
were measured by a high performance liquid
chromatography-mass spectrometry assay. Each cat
received an immunogenically mismatched renal allograft
and native kidney nephrectomy. Tacrolimus
dosage was modified to maintain a target blood concentration
of 5 to 10 ng/mL. Cats were euthanatized
if plasma creatinine concentration exceeded 7 mg/dL,
body weight loss exceeded 20%, or on day 50 after
surgery. Kaplan-Meier survival curves were plotted for
6 cats treated with tacrolimus and for 8 cats with
renal transplants that did not receive immunosuppressive
Results—Mean (± SD) values of elimination half-life,
time to maximum concentration, maximum blood concentration,
and area under the concentration versus
time curve from the last dose of tacrolimus to 12 hours
later were 20.5 ± 9.8 hours, 0.77 ± 0.37 hours, 27.5 ±
31.8 ng/mL, and 161 ± 168 hours × ng/mL, respectively.
Tacrolimus treated cats survived longer (median, 44
days; range, 24 to 52 days) than untreated cats (median,
23 days; range, 8 to 34 days). On histologic evaluation,
3 cats had evidence of acute-active rejection, 1 cat
had necrotizing vasculitis, and 2 cats euthanatized at
study termination had normal appearing allografts.
Conclusions and Clinical Relevance—Tacrolimus
may be an effective immunosuppressive agent for
renal transplantation in cats. (Am J Vet Res 2003;64:926–934)