Objective—To describe clinical signs, diagnostic findings,
and outcome in dogs with idiopathic intrahepatic
Procedure—Medical records of dogs with portal
hypertension of intra-abdominal origin were reviewed.
Dogs with intra-abdominal portal hypertension of vascular
causes or with hepatic histopathologic changes
consistent with severe diffuse hepatobiliary disease
were excluded. History and results of physical examination,
clinicopathologic tests, diagnostic imaging
studies, histologic examination, and treatment were
summarized. Outcome was determined in 26 dogs.
Results—Dogs were referred most often because of
ascites, intermittent vomiting or diarrhea, and polydipsia
of several months' duration. Microcytosis, high
serum alkaline phosphatase and alanine transaminase
activities, hepatic dysfunction, urine specific gravity ≤
1.021, and abdominal transudate were the predominant
clinicopathologic features. Microhepatia, abdominal
effusion, and multiple anomalous venous anastomoses
were the major findings of diagnostic imaging.
Hepatic histopathologic changes were consistent
with idiopathic noncirrhotic portal hypertension and
were indistinguishable from those of dogs with surgically
created portocaval anastomosis. Outcome was
determined for 19 dogs released from hospital; 13
dogs remained healthy with mostly palliative treatment
for periods of 5 months to 9 years.
Conclusions and Clinical Relevance—The clinical
signs, clinicopathologic test results, portal pressure,
and gross appearance of the liver of dogs with idiopathic
noncirrhotic portal hypertension may be identical
to those of dogs with cirrhosis; therefore liver
biopsy is crucial. Because the prognosis for idiopathic
noncirrhotic portal hypertension is generally favorable,
owners of affected dogs should be discouraged from
choosing euthanasia. (J Am Vet Med Assoc 2000;
OBJECTIVE To investigate the cytotoxic effects of azathioprine, 6-mercaptopurine, and 6-thioguanine on canine hepatocytes.
SAMPLE Commercially available cryopreserved canine primary hepatocytes.
PROCEDURES The study consisted of 2 trials. In trial 1, hepatocytes were incubated with azathioprine, 6-mercaptopurine, or 6-thioguanine at 1 of 6 concentrations (0.468, 0.937, 1.875, 3.750, 7.500, or 15.000 μmol/L) for 24, 48, or 72 hours. At each time, cell viability and lactate dehydrogenase (LDH) activity were determined for each thiopurine-concentration combination, and alanine aminotransferase (ALT) activity was determined for cells incubated with each thiopurine at a concentration of 15 μmol/L. In trial 2, hepatocytes were incubated with azathioprine, 6-mercaptopurine, or 6-thioguanine at 1 of 3 concentrations (18.75, 37.50, or 75.00 μmol/L) for 24 hours, after which the free glutathione concentration was determined for each thiopurine-concentration combination and compared with that for hepatocytes incubated without a thiopurine (control).
RESULTS Incubation of hepatocytes with each of the 3 thiopurines adversely affected cell viability in a time- and concentration-dependent manner; however, this decrease in cell viability was not accompanied by a concurrent increase in LDH or ALT activity. Likewise, free glutathione concentration for hepatocytes incubated for 24 hours with supratherapeutic thiopurine concentrations (> 18.75 μmol/L) did not differ significantly from that of control cells.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that thiopurines adversely affected the viability of canine hepatocytes in a time- and concentration-dependent manner but had a nonsignificant effect on the LDH and ALT activities and free glutathione depletion of those hepatocytes.
Objective—To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses.
Animals—10 client-owned horses with IMMK.
Procedures—Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained). Equine IgG, IgM, and IgA antibodies were used to detect corneal immunoglobulin via direct immunofluorescence (10 eyes). Serum and aqueous humor (AH) samples from 3 horses with IMMK were used to detect circulating and intraocular IgG against corneal antigens via indirect immunofluorescence on unaffected equine cornea.
Results—Percentage scores (scale, 0 to 4) of cells expressing CD3 (median, 2.35 [range, 0.2 to 3.7]; mean ± SD, 2.36 ± 1.08) were significantly greater than scores of cells expressing CD79a (median, 0.55 [range, 0 to 1.5]; mean, 0.69 ± 0.72). All samples stained positively for CD4- and CD8-expressing cells, with no significant difference in scoring. All samples stained positively for IgG, IgM, and IgA. No serum or AH samples collected from horses with IMMK reacted with unaffected equine cornea.
Conclusions and Clinical Relevance—Pathogenesis of superficial stromal IMMK included cell-mediated inflammation governed by both cytotoxic and helper T cells. Local immunoglobulins were present in affected corneas; however, corneal-binding immunoglobulins were not detected in the serum or AH from horses with IMMK.
Objective—To evaluate the anterior chamber approach and energy levels for endoscopic cyclophotocoagulation (ECPC) and assess ECPC-induced tissue damage in phakic eyes of bovine cadavers.
Sample—12 bovine cadaver eyes.
Procedures—Angle of reach was measured in 6 eyes following placement of a curved endoscopic probe through multiple corneal incisions. In another 6 eyes, each ocular quadrant underwent ECPC at 1 of 3 energy levels (0.75, 0.90, and 1.05 J) or remained untreated. Visible effects on tissues (whitening and contraction of ciliary processes) were scored (scale of 0 [no effects] to 6 [severe effects]), and severity and extent of histologic damage to the pigmented and nonpigmented ciliary epithelium and fibromuscular stroma were each scored (scale of 0 [no effect] to 3 [severe effect]) and summed for each quadrant. Overall mean scores for 6 quadrants/treatment were calculated.
Results—Mean ± SD combined angle of reach was 148 ± 24° (range, 123 ± 23° [ventromedial] to 174 ± 11° [dorsolateral]). At the 0.75-, 0.90-, and 1.05-J levels, mean visible tissue effect scores were 3.12 ± 0.47, 3.86 ± 0.35, and 4.68 ± 0.58, respectively; mean histologic damage scores were 4.79 ± 1.38 (mild damage), 6.82 ± 1.47 (moderate damage), and 9.37 ± 1.42 (severe damage), respectively. Occasional popping noises (venting of vaporized interstitial water) were heard at the 1.05-J level.
Conclusions and Clinical Relevance—Multiple incisions were necessary to facilitate 360° ECPC treatment in bovine eyes. For ECPC in vivo, the 0.75- and 0.90-J energy levels had the potential to effectively treat the ciliary epithelium.