Factors predictive of response to cyclosporin treatment for severe, steroid-resistant ulcerative colitis.

OBJECTIVE: Cyclosporin-A (CSA) has been demonstrated to be effective for treatment of severe, steroid-resistant ulcerative colitis (UC). Use of CSA has been limited, however, because of low 1-yr response rates and the potential for complications. The aim of this study is to define clinical and laboratory factors predictive of response in severe, steroid-resistant UC. METHODS: A retrospective review of 36 cases of severe, steroid-resistant UC treated with CSA was performed. Intravenous (i.v.) CSA was administered at an initial dose of 2.5 mg/kg, and oral (p.o.) CSA was given as twice the i.v. dose. Clinical response was recorded and logistic regression analysis was performed on clinical and laboratory factors for prediction of response to CSA. RESULTS: Of 36 patients, 25 responded to i.v. CSA and were switched to p.o. CSA. Of the 25, 13 required colectomy by 9 months. The other 12 patients had a sustained response to CSA and avoided colectomy at 9 months. Overall, 24 of 36 patients treated with CSA required colectomy by 9 months. A high percentage of band neutrophils (bands) on admission was found to be a significant predictor of response to CSA. CONCLUSIONS: Bands on admission are predictive of response to CSA and ultimately, the requirement for surgery in steroid-resistant UC.

A pilot study of splenic and whole body retention of autologous radiolabeled leukocytes in the assessment of severity in inflammatory colitis.

OBJECTIVE: To assess the splenic and whole body retention of radiolabeled autologous leukocytes over 24 or 48 h as measures of the severity of colitis. METHODS: Eleven patients with colitis underwent standardized clinical, endoscopic, histological, and 111In-labeled leukocyte scintigraphy. A logistic discriminant analysis was used to estimate weighting factors for morphological indices, serum albumen, and stool excretion of 111In over 24 h that predicted the clinical assessment of severity. Subsequently, Spearman rank correlation analysis estimated associations among reductions in spleen and whole body radioactivity and the derived indices of inflammation. RESULTS: The reduction in spleen counts over 24 h correlates significantly with morphological indices (rs = 0.83, p < 0.005) and with serum albumen and stool 111In (functional index, rs = 0.77, p < 0.01). Similarly, the reduction in whole body 111In over 48 h correlates significantly with the combined index (rs = 0.8) and with the morphological and functional index separately (rs = 0.72 and 0.79, respectively). CONCLUSION: This pilot study identified weighting factors for morphological and functional indices in assessing severity of colitis; reduction in whole body and splenic retention of radioactivity was sufficient for evaluation of severity of colitis without the need for stool collections.

111In-oxine-labelled granulocyte dosimetry in normal subjects.

The aim of this study was to determine organ uptake and dosimetry in human subjects using 111In granulocytes obtained by ficoll-hypaque purification. Anterior-posterior whole-body imaging was performed at 1, 3, 5, 24 and 48 h after injection of approximately 18.5 MBq (0.5 mCi) 111In granulocytes in 10 normal volunteers. Utilizing relative geometric mean analysis, the fraction of injected activity (FIA) was determined at each imaging time for the kidney, liver, lungs, bone marrow, spleen and whole-body remainder. Residence time was determined by integration of the bi-exponential fit of the FIA data over time. Curve fitting was performed with SAAM software (University of Washington). Red marrow uptake was calculated from activity in the L3-L4 vertebrae and iliac crests. Total body marrow uptake was extrapolated from these data using ICRP 23. Dose was determined with MIRDOSE 2 for the various organs. The liver had the highest organ uptake (40.3% at 48 h). The spleen, liver, red marrow, kidney and lung doses were 4.1, 1.6, 0.8, 0.5 and 0.4 mGy MBq-1, respectively. Urinary and stool excretion was negligible and blood clearance half-time was 6.9 h. Using current methods providing improved quantification of organ uptake and dosimetry, our results confirm the liver, spleen, bone marrow,lungs and kidneys to be the principal target organs of 111In granulocytes.

Olfactory bulbectomy: influences on maternal behavior in primiparous and multiparous rats.

Bilateral olfactory bulb ablation resulted in deficits in several components of maternal behavior in lactating, primiparous female rats. These females frequently cannibalized pups shortly after parturition. Furthermore, bilaterally bulbectomized, primiparous females spent less time nursing their pups and retrieved fewer pups than unilaterally bulbectomized or sham-operated females. In contrast to the situation in primiparous females, in multiparous females bilateral bulbectomy failed to influence any parameter of maternal behavior.