The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), ␣-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP, HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P Ͻ .02) increased in dogs with CIBDAI scores Ն5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r ϭ 0.82, P Ͻ .0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P Ͻ .0001) decreased CIBDAI and CRP values but significantly (P Ͻ .0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.

Compared with the current commercial process, the new IGIV-C manufacturing process produces a more highly purified preparation that contains slightly higher levels of IgG4 and retains antibody activities required for clinical efficacy.

The Ames Salmonella/microsomal activation mutagenesis assay has been modified to improve sensitivity and reproducibility to complex mixtures derived from the refining and processing of petroleum. Oil samples were dissolved in cyclohexane and subsequently extracted with dimethyl sulfoxide to produce aqueous compatible solutions which readily interact with tester bacteria. Also, the liver homogenate (S-9) and NADP cofactor concentrations were increased and hamster rather than rat liver S-9 was used. The initial slope of the dose response curve relating mutagenicity (revertants per plate) to the dose of extract added was used as an index of mutagenic activity; this slope was obtained through a computerized curve fitting procedure. The modified assay was used to rank 18 oil samples for mutagenic activity; this ranking correlates highly (r = 0.92) with potency rankings of the same samples previously determined from dermal carcinogenicity bioassays. Sensitivity and reproducibility of the assay are sufficient to permit routine use for detecting potential carcinogenic activity of individual refinery streams and blends which contain components boiling above 500 degrees F.

Results of five previously unpublished studies of the genotoxicity of naphthalene are presented and extensively discussed in relation to the large database that exists in the published literature. According to the published literature, naphthalene has not induced gene mutations in bacterial assays or in a metabolically competent human cell line. However, naphthalene has caused cytotoxicity in some cell lines, and induced clastogenicity in Chinese hamster ovary (CHO) cells, in a human lymphoblastoid cell line, and in preimplantation mouse embryos. Some naphthalene metabolites were cytotoxic, but only naphthoquinones produced chromosomal damage in vitro. No chromosomal damage was observed in vivo in bone marrow erythrocytes from treated mice; however, a positive response was reported in a Drosophila assay for wing somatic mutation and recombination. The five unpublished studies of naphthalene genotoxicity include three studies in vitro (two Ames bacterial assays and an in vitro unscheduled DNA synthesis assay) and two in vivo (mouse micronucleus and in vivo unscheduled DNA synthesis). Naphthalene was inactive in all five studies, in agreement with reports in the published literature. Chronic inhalation of naphthalene over 2 yr induced an increased incidence of benign alveolar/bronchial adenomas in female mice, and nasal epithelial tumors in both sexes of rats. Inflammation, tissue damage, and subsequent regenerative hyperplasia at target organ sites occurred in both species. Results of standard genetic toxicity assays suggest that naphthalene is not likely to be genotoxic in vivo. Since the in vitro results come primarily from assays utilizing liver-mediated activation systems, and the in vivo results come from rodent organs that are not targets for tumors, tests using naphthalene-sensitive rodent tissues would determine the applicability of current data in addressing the mechanisms of these species and site-specific cancers. The standard assays reported here may be useful in predicting potential health hazard in other species, or in humans, in whom there are few reported instances of naphthalene-induced cancer, especially as more data on species-specific differences in naphthalene metabolism become available. Despite present data limitations, a threshold mechanism for tumorigenesis can be proposed. The absence of naphthalene-induced gene mutation and the presence of cytotoxicity and some chromosomal events in vitro are consistent with a threshold-related mechanism of tumor induction, driven by cytotoxicity and cell regeneration, followed by genetic events, or by accumulation of naphthalene at specific target sites to allow in situ formation of a genotoxic metabolite to trigger or enhance spontaneous tumor development.

Vitamin D-dependent rickets type 2 in a four-month-old cat A 4-month-old male domestic shorthair cat was examined because of lethargy, vomiting, diarrhea, muscle tremors, and mydriasis. Laboratory evaluation revealed hypocalcemia, hyperphosphatemia, and high intact parathormone and calcitriol concentrations. Findings were compatible with a diagnosis of vitamin D-dependent rickets type 2. Treatment consisted of oral administration of calcium and calcitriol supplements. During the subsequent 18 months, the cat remained clinically normal. Treatment with oral calcium supplements was eventually discontinued, and the cat was able to maintain serum calcium concentrations within reference limits.