Retrospective evaluation of risk factors and treatment outcome predictors in cats presenting to the emergency room for constipation.

OBJECTIVES: Constipation is a common complaint in cats presenting to the emergency room and can become a frustrating recurrent condition. Despite widespread anecdotal reports of risk factors for constipation, at the time of writing there have been no studies supporting these associations or assessing treatment outcomes. The aim of this study was to identify risk factors in the signalment, history, physical examination and clinicopathologic findings of cats presenting to the emergency room for constipation. In addition, we aimed to assess factors contributing to the success or failure of enemas administered to these cats. METHODS: A medical record search identified 189 cats with a diagnosis of constipation/obstipation that were treated and discharged by the emergency service at an academic veterinary hospital. Data regarding signalment, medical history, physical examination and clinicopathologic findings, as well as treatments performed, were recorded. Ninety-nine cats presenting to the emergency room for other reasons were identified as controls. Statistical analysis was performed to assess risk factors for constipation, as well as success/failure of enema treatments. RESULTS: Older, overweight cats and cats with chronic kidney disease or previous episodes of constipation were found to be at increased risk of constipation (P <0.0001, P = 0.0004, P = 0.0046 and P <0.0001, respectively). Ionized calcium levels were significantly higher in constipated cats, though varied significantly within the cohort (P = 0.0133). Cats noted to be painful on abdominal palpation were less likely to defecate following an enema. Adjunctive treatments (fluids, laxatives) increased the likelihood of a successful enema but were not statistically significant. CONCLUSIONS AND RELEVANCE: Older, overweight cats with a history of constipation or chronic kidney disease are more likely to present for constipation. Further studies are needed to determine the most appropriate treatment protocol in an urgent care setting.

A role for the copper transporter Ctr1 in the synergistic interaction between hyperthermia and cisplatin treatment.

PURPOSE: Hyperthermia enhances cytotoxic effects of chemotherapeutic agents such as cisplatin. However, the underlying molecular mechanisms remain unclear. We hypothesised that hyperthermia increases cisplatin accumulation and efficacy by modulating function of copper transport protein 1 (Ctr1), a major regulator of cellular cisplatin uptake. We examined the significance of Ctr1 in the synergistic interaction between hyperthermia and cisplatin. We assessed the importance of cisplatin- and hyperthermia-induced Ctr1 multimerisation in sensitising cells to cisplatin cytotoxicity. MATERIALS AND METHODS: Ctr1 protein levels and cisplatin sensitivities were assessed in bladder cancer cell lines with immunoblotting and clonogenic survival assays. Using Myc-tagged-Ctr1 HEK293 cells, we assessed the effect of hyperthermia on Ctr1 multimerisation with immunoblotting. The effect of hyperthermia on cisplatin sensitivity and accumulation was assessed in wild-type (WT) and Ctr1 knockout (Ctr1-/-) mouse embryonic fibroblasts (MEFs) with clonogenic assays and inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Increased Ctr1 protein expression was observed for the most cisplatin-sensitive bladder cancer cell lines and MEFs. Heat-induced increase in Ctr1 multimerisation with cisplatin was observed in Myc-tagged Ctr1 cells. Hyperthermia enhanced cisplatin-mediated cytotoxicity in WT more than Ctr1-/- cells (dose modifying factors 1.75 versus 1.4, respectively). WT cells accumulated more platinum versus Ctr1-/- cells; this was further increased by hyperthermia in WT cells. CONCLUSIONS: Hyperthermia enhanced cisplatin uptake and cytotoxicity in WT cells. Heat increased Ctr1 activity by increasing multimerisation, enhancing drug cytotoxicity. Furthermore, Ctr1 protein profiles of bladder tumours, as well as other tumour types, may predict their response to cisplatin and overall efficacy of treatment.