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Objective— To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. Study Design— Prospective, pilot study. Animals— Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. Methods— All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. Results— Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. Conclusions— In this experimental model, a CAP–CsA–prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. Clinical Relevance— A CAP–CsA–prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

Background and Objectives The first objective of this study was to evaluate the performance of fluorescence spectroscopy for diagnosing pre-cancers in stratified squamous epithelial tissues in vivo using two different probe geometries with (1) overlapping versus (2) non-overlapping illumination and collection areas on the tissue surface. Probe (1) and probe (2) are preferentially sensitive to the fluorescence originating from the tissue surface and sub-surface tissue depths, respectively. The second objective was to design a novel, angled illumination fiber-optic probe to maximally exploit the depth-dependent fluorescence properties of epithelial tissues. Study Design/Materials and Methods In the first study, spectra were measured from epithelial pre-cancers and normal tissues in the hamster cheek pouch and analyzed with a non-parametric classification algorithm. In the second study, Monte Carlo modeling was used to simulate fluorescence measurements from an epithelial tissue model with the angled illumination probe. Results An unbiased classification algorithm based on spectra measured with probes (1) and (2), classified pre-cancerous and normal tissues with 78 and 94% accuracy, respectively. The angled illumination probe design provides the capability to detect fluorescence from a wide range of tissue depths in an epithelial tissue model. Conclusions The first study demonstrates that fluorescence originating from sub-surface tissue depths (probe (2)) is more diagnostic than fluorescence originating from the tissue surface (probe (1)) in the hamster cheek pouch model. However in general, it is difficult to know a priori the optimal probe geometry for pre-cancer detection in a particular epithelial tissue model. The angled illumination probe provides the capability to measure tissue fluorescence selectively from different depths within epithelial tissues, thus obviating the need to select a single optimal probe design for the fluorescence-based diagnosis of epithelial pre-cancers. Lasers Surg. Med. 34:25–38, 2004. © 2004 Wiley-Liss, Inc.

Fertilized eggs of ring-necked pheasants (Phasianus colchicus) were injected into the albumin or yolk with vehicle or graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.01, 0.1, 1, 10, 100, 1,000, 10,000, or 100,000 pg TCDD/g egg) on day 0 of embryonic development and toxicity was assessed in 1-d-old hatchlings and 28-d-old chicks. The most sensitive effect of in ovo TCDD exposure was induction of hepatic ethoxyresorufin-O-deethylase (EROD) activity in 1-d-old hatchlings. The ED50 for this response was 312 pg TCDD/g egg. Embryo mortality was the most sensitive sign of toxicity. The TCDD dose that caused 50% mortality above control (LD50) when injected into the egg albumin or yolk was 1,354 and 2,182 pg TCDD/g egg, respectively. At egg TCDD doses up to and including 1,000 pg TCDD/g egg, no effect was detected in 1-d-old hatchlings and 28-d-old chicks in body growth, organ weights, carcass morphometrics, incidence of edema, or incidence of histological alterations in the liver, spleen, heart, Bursa of Fabricius, or thymus. Egg TCDD doses as high as 1,000 pg TCDD/g egg also had no effect on cardiac morphometrics or incidence of cardiac malformations in 1-d-old hatchlings, or on antibody-mediated immunity in 28-d-old chicks. We conclude that embryo mortality is the most sensitive sign of TCDD toxicity in the ring-necked pheasant following in ovo exposure. The ring-necked pheasant embryo is less sensitive than the chicken (Gallus domesticus) embryo and more sensitive than the eastern bluebird (Sialia sialis) embryo to TCDD toxicity.