Objective—To determine whether transitional cell
carcinoma (TCC) cells incubated in media containing
5-aminolevulinic acid (ALA) would produce sufficient
protoporphyrin IX (PpIX) to cause lethal phototoxic
effects when exposed to 635-nm light.
Sample Population—Canine TCC cells (K9TCC).
Procedure—Cultured K9TCC cells were exposed to
graded doses of ALA, and PpIX concentrations were
determined. Cells then were exposed to various
doses of 635-nm light from a diode laser, and cell viability
Results—Production of PpIX was dependent on time
and dose of ALA. The K9TCC cells incubated with ALA
produced sufficient PpIX to cause lethal phototoxic
effects when exposed to 635-nm light. Phototoxic
effects were dependent on time and dose of ALA.
Increasing laser power density and energy density
decreased cell survival.
Conclusions and Clinical Relevance—ALA is an
effective photosensitizer for in vitro photodynamic
treatment of K9TCC cells. Further studies are warranted
to assess the safety and efficacy of ALA as a
photosensitizer for use in treating dogs with TCC.
Impact for Human Medicine—On the basis of this
study, dogs with TCC may be useful in the development
of protocols for ALA-based photodynamic therapy
of humans affected with muscle-invasive bladder
cancer. (Am J Vet Res 2003;64:131–136)
Objective—To determine whether the presence of anemia (Hct ≤ 37%) at the time of diagnosis of lymphoma is a negative prognostic indicator for response to treatment and survival time in dogs that are undergoing chemotherapy.
Design—Retrospective case series.
Animals—96 dogs with lymphoma that were receiving chemotherapy.
Procedures—Information regarding signalment, initial hematologic data, chemotherapy protocol, clinical response, and date of death was retrospectively collected from medical records of dogs with lymphoma. Univariate, multivariate, and survival analyses were performed to determine the effect of anemia on initial response to chemotherapy and on survival time.
Results—Overall, dogs without anemia (n = 56) were 4 times as likely as dogs with anemia (40) to have a complete response following chemotherapy. Anemic dogs had a significantly shorter median survival time (139 days), compared with survival time of nonanemic dogs (315 days). Subset analysis of dogs with multicentric lymphoma (matched for clinical stage and chemotherapy protocol) revealed that the dogs with anemia (n = 24) had a significantly shorter median survival time (101 days), compared with survival time of dogs without anemia (24; 284 days). Other variables were not associated with survival time.
Conclusions and Clinical Relevance—These findings suggested that anemia is a negative prognostic factor for dogs with lymphoma that are undergoing chemotherapy. Further investigation will be necessary to determine the impact of resolution of anemia on clinical outcome in dogs with lymphoma.
Objective—To describe diseases, prognosis, and clinical
outcomes associated with extreme neutrophilic
leukocytosis in cats.
Animals—104 cats with extreme neutrophilic leukocytosis.
Procedure—Medical records from 1991 to 1999 were
examined to identify cats that had ≥ 50,000 WBC/µl
with ≥ 50% neutrophils. Signalment, absolute and differential
WBC counts, rectal temperature, clinical or
pathologic diagnosis, duration and cost of hospitalization,
and survival time were reviewed.
Results—Mean age of cats was 8.3 years, mean
WBC count was 73,055 cells/µl, and mean absolute
neutrophil count was 59,046 cells/µl. Mean duration
of hospitalization was 5.9 days, and mean cost of hospitalization
was $2,010. Twenty-nine (28%) cats were
febrile, and 63 (61%) cats died. Overall median survival
time was 30 days. Cats with neoplasia were
nearly 14 times as likely to die unexpectedly as cats
with other diseases.
Conclusions and Clinical Relevance—Extreme neutrophilic
leukocytosis was associated with a high mortality
rate. The prognostic importance of extreme neutrophilic
leukocytosis should not be overlooked. Cats and
dogs have similar diseases, mortality rates, and treatment
costs associated with extreme neutrophilic leukocytosis.
(J Am Vet Med Assoc 2001;218:736–739)
Objective—To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS4), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS4-based photodynamic therapy (PDT) in pet dogs with naturally occurring tumors.
Animals—Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms.
Procedures—For the study of acute toxicosis, mice were given graded doses of ZnPcS4. To determine safety, a rapid-titration phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs was conducted.
Results—In mice, administration of ≥ 100 mg of ZnPcS4/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS4 doses ≤ 4 mg/kg induced no signs of toxicosis and resulted in partial to complete tumor responses in 10 of 12 dogs 4 weeks after PDT. Tumor remission was observed with ZnPcS4 doses as low as 0.25 mg/kg.
Conclusions and Clinical Relevance—A conservative starting dose of ZnPcS4 was arrived at on the basis of mouse toxicosis findings. Zinc phthalocyanine tetrasulfonate–based PDT was tolerated well by all dogs and warrants further study. The identification of the maximum tolerated dose through traditional phase I clinical trials may be unnecessary for evaluating novel PDT protocols.
Objective—To determine whether there was a
decline in the percentage of dogs undergoing necropsies
and whether there was substantial agreement or
disagreement between clinical and pathologic diagnoses.
Procedure—Medical records of hospitalized dogs
that died or were euthanatized and necropsied at a
veterinary teaching hospital in 1989 and 1999 were
reviewed. Clinical and pathologic diagnoses were
recorded and compared.
Results—There was a significant decline in the
necropsy rate of hospitalized dogs that died or were
euthanatized in 1999, compared with 1989. In both
1989 and 1999, there was disagreement between the
clinical and pathologic diagnoses in approximately a
third of the cases.
Conclusions and Clinical Relevance—Despite
improved diagnostic methods, the accuracy of diagnosis
did not improve significantly in 1999, compared
with 1989. Necropsy is the best method to assess
overall diagnostic accuracy. Increased availability of
teaching funds may promote efforts to have necropsies
performed in veterinary teaching hospitals. ( J Am
Vet Med Assoc 2004;224:403–406)
Objective—To compare histologic artifacts caused by
carbon dioxide (CO2) or 810-nm diode surgical lasers
used to obtain small biopsy specimens of skin from
Procedure—21 skin biopsy specimens were collected
from each dog. Three biopsy specimens were
obtained with a CO2 or an 810-nm diode laser at 3
operating settings each, and 3 biopsy specimens
were obtained with a 6-mm biopsy punch instrument
(controls). After processing, biopsy specimens were
examined for artifacts related to laser-tissue interactions.
Microscopically visible char was measured
from the lateral edge of each specimen obtained with
Results—There were no significant differences
among mean char distances in biopsy specimens
obtained with the CO2 laser at various settings. Mean
char distance was significantly greater in all skin biopsy
specimens obtained with the diode laser, compared
with those obtained with the CO2 laser. Mean
char distance was significantly greater in biopsy specimens
obtained with the 810-nm diode laser at high
power, compared with biopsy specimens obtained
with the 810-nm diode laser at low power.
Conclusions and Clinical Relevance—Results indicated
that the CO2 laser caused less thermal injury at
margins of skin biopsy specimens; therefore, if a surgical
laser is used for removal of cutaneous masses
or to obtain skin biopsy specimens, use of the CO2
laser is recommended. Veterinarians performing a
biopsy by using a surgical laser should be aware that
laser-induced artifacts may render small biopsy specimens
useless for providing accurate histologic diagnosis.
(J Am Vet Med Assoc 2004;225:1562–1566)
Objective—To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder.
Animals—14 client-owned dogs with histologically confirmed TCC of the urinary bladder.
Procedures—Each dog was treated with cisplatin (50 mg/m2, IV, q 21 d [reduced to 40 mg/m2, IV, q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment.
Results—5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively.
Conclusions and Clinical Relevance—Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m2) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.