Methods and Aims-For the detection of colorectal neoplasia, 192 consecutive patients had colonoscopy to evaluate the sensitivity and specificity of three faecal occult blood tests (FOBT (Gut 1996; 39: 722-725) Australia Ltd) uses a monoclonal antibody that is specific for human haemoglobin, which theoretically should decrease the number of false positive test results. The BM Test colon albumin (BMCA) (Boehringer Mannheim, UK) is designed to detect human albumin present in the faecal sample, which may be associated with colorectal neoplasia.The aim of this study is to evaluate the sensitivity and specificity of these three FOBTs as a means of detecting colorectal neoplasia. From March 1991 until November 1992 consecutive patients who required colonoscopy for the investigation of gastrointestinal symptoms or for 'polyp surveillance' follow up (see Figure), were recruited for study. In no case was colonoscopy being performed for previously positive FOBTs and patients with a history of overt gastrointestinal bleeding were excluded. No patient had undergone previous colonic resectional surgery. Patients were asked to start the testing of stools five days before hospital admission to ensure enough time to complete the three day regimen before bowel preparation. There were no dietary restrictions placed on the patients and regular medications were continued. Methods Patients

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Background: Drug resistance and chemotherapy-induced peripheral neuropathy continue to be significant problems in the successful treatment of acute lymphoblastic leukemia (ALL). 5,7-Dibromo-N-alkylisatins, a class of potent microtubule destabilizers, are a promising alternative to traditionally used antimitotics with previous demonstrated efficacy against solid tumours in vivo and ability to overcome P-glycoprotein (P-gp) mediated drug resistance in lymphoma and sarcoma cell lines in vitro. In this study, three di-brominated N-alkylisatins were assessed for their ability to retain potency in vincristine (VCR) and 2-methoxyestradiol (2ME2) resistant ALL cell lines. For the first time, in vitro neurotoxicity was also investigated in order to establish their suitability as candidate drugs for future use in ALL treatment. Methods: Vincristine resistant (CEM-VCR R) and 2-methoxyestradiol resistant (CEM/2ME2-28.8R) ALL cell lines were used to investigate the ability of N-alkylisatins to overcome chemoresistance. Interaction of N-alkylisatins with tubulin at the the colchicine-binding site was studied by competitive assay using the fluorescent colchicine analogue MTC. Human neuroblastoma SH-SY5Y cells differentiated into a morphological and functional dopaminergic-like neurotransmitter phenotype were used for neurotoxicity and neurofunctional assays. Two-way ANOVA followed by a Tukey's post hoc test or a two-tailed paired t test was used to determine statistical significance. Results: CEM-VCR R and CEM/2ME2-28.8R cells displayed resistance indices of > 100 to VCR and 2-ME2, respectively. CEM-VCR R cells additionally displayed a multi-drug resistant phenotype with significant cross resistance to vinblastine, 2ME2, colchicine and paclitaxel consistent with P-gp overexpression. Despite differences in resistance mechanisms observed between the two cell lines, the N-alkylisatins displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell line. The N-alkylisatins proved to be significantly less neurotoxic towards differentiated SH-SY5Y cells than VCR and vinblastine, evidenced by increased neurite length and number of neurite branch points. Neuronal cells treated with 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin showed significantly higher voltage-gated

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