A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Bivariate flow cytometric analysis of murine intestinal epithelial cells for cytokinetic studies.

The heterogeneous nature of the small intestine and the lack of methods to obtain pure crypt populations has, in the past, limited the application of standard flow cytometric analysis for cytokinetic studies of the proliferating crypts. We describe a flow cytometric technique to discriminate crypt and villus cells in an epithelial cell suspension on the basis of cell length, and to measure the DNA content of the discriminated subpopulations. Our data indicate that bivariate analysis of a mixed epithelial cell suspension can be used to distinguish mature villus cells, G1 crypt cells, and S-phase crypt cells. In addition, continuous labeling studies suggest that the position of a cell on the cell length axis reflects epithelial cell maturity. We applied this flow cytometric technique to determine the cytokinetic nature of epithelial cells obtained by sequential digestion of the small intestine.

Relationship between surviving clonogenic crypt fraction and animal lethality after cytosine arabinoside (Ara-C) exposure.

We have measured animal morbidity and the fraction of clonogenic crypt cells following administration of several doses of Ara-C as an infusion over a 24 h period. A nonlinear relationship between reduction in crypt cell survival and Ara-C induced animal lethality was observed, indicating that factors other than crypt cell toxicity contribute to lethality in conventionally-maintained mice. A dose of 100 mg/kg Ara-C reduced the fraction of surviving clonogenic crypt cells to 7 X 10(-3) without animal lethality. However, 300 mg/kg reduced crypt clonogenic cell survival only to 4 X 10(-3) while killing 50 percent of the animals. Maintenance of the animals on acid water before and after Ara-C treatment reduced animal lethality substantially. The magnitude of the reduction of clonogenic crypt cells was incompatible with S-phase specific toxicity as the only cytotoxic mechanism, and suggested that cell recruitment and crypt cell kill due to unbalanced growth are also operative during Ara-C infusion. In addition, the detection of a subpopulation of clonogenic crypt cells which was resistant to killing by Ara-C has important clinical implications and warrants further investigation. These results are substantially different than those found after radiation where, with high radiation doses, the fraction of clonogenic crypt cells decreases exponentially, and where a close relation between reduction in clonogenic crypt cell survival and animal lethality has been established.