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We aimed to assess elective day surgery patients' understanding of the reason for pre-operative fasting. One hundred adult patients presenting to the peri-operative unit for day procedures requiring general anaesthesia were surveyed before discharge. All day-stay, adult patients able to complete a questionnaire in English were included. Only 22% (95%CI [14,31]) of patients correctly understood why fasting was necessary. Patients who did not understand were nearly five times more likely to underrate the importance of compliance (risk ratio 4.65, 95%CI [1.2,18]). Two per cent (95%CI [0.2,7]) of patients reported actual non-compliance, and 4% (95%CI [1,10]) stated they would consider misrepresenting their fasting status if it was inconvenient for them to have their surgery postponed. The results of this study suggest a need to better inform day surgery patients about the reason for pre-operative fasting. A better understanding of the need for pre-operative fasting may lead to improved compliance and patient safety.

UFT (BMS-200604, Uftoral) is an oral fluoropyrimidine that combines uracil and the 5-fluorouracil (5-FU) prodrug, ftorafur, in a 4:1 molar ratio with single-agent activity in breast and gastrointestinal cancers. In vitro studies have shown that irinotecan downregulates thymidylate synthase (TS) expression in tumour cells, leading to synergy between irinotecan and 5-FU that is maximal when irinotecan is given 24 h prior to 5-FU. Given this observed synergy and the confirmatory clinical activity of combination therapy with 5-FU, leucovorin (LV) and irinotecan, we performed a phase I trial to determine the maximum tolerated doses (MTD) of UFT, LV, and irinotecan. Treatment consisted of irinotecan administered as a 90-min intravenous (i.v.) infusion on day 1 followed by twice daily oral UFT/LV on days 2-15, repeated every 21 days. Initial doses were irinotecan 200 mg/m(2) and UFT 200 mg/m(2)/day, with LV dose fixed at 60 mg/day. 31 patients received a total of 130 cycles of UFT/LV and irinotecan. 3 of 9 patients experienced grade 3/4 diarrhoea at the highest dose level of irinotecan 310 mg/m(2) and UFT 300 mg/m(2)/day. Other toxicities included neutropenia, anaemia, alopecia, nausea/vomiting and fatigue. Further dose escalation was not pursued since this level of toxicity was appropriate for future phase II study. One patient with colorectal cancer experienced a partial response and 9 patients with non-small cell lung, colorectal and gastro-oesophageal junction carcinomas had disease stabilisation lasting 4-26 (median 6) cycles. Methylenetetrahydrofolate reductase (MTHFR) C677T genotype was analysed in peripheral mononuclear cells (PMNs) obtained from 24 patients. 2 patients had the homozygous TT polymorphism and 1 of them had grade 3 diarrhoea at the first dose level. Irinotecan on day 1 followed by a 14-day course of oral UFT/LV beginning on day 2 is well tolerated, and suitable for testing in several tumour types. Doses recommended for further study on this schedule are irinotecan 310 mg/m(2) and UFT 300 mg/m(2)/day, with LV 60 mg/day.

Tumour necrosis factor (TNF)-alpha contributes to the pathogenesis of many inflammatory diseases. Recombinant soluble TNF receptor fusion proteins (sTNFR:Ig) are potent TNF antagonists, both in vitro and in vivo. The concentration of serum amyloid A (SAA) increases by up to 1000-fold during inflammation, largely owing to cytokine-driven transcriptional upregulation. A reporter plasmid, comprising the proximal 0.7 kb of the human SAA2 promoter fused to a luciferase gene, was used in transient transfection experiments in human HepG2 hepatoma cells to assess the quantitative and qualitative TNF antagonist properties of a construct in which sTNFR:Ig synthesis is under the control of a chimera of the SAA2 promoter and a tat/HIV element. The SAA2-tat/HIV-sTNFR:Ig construct retained the fine-tuned cytokine responsiveness of the SAA2 promoter, while exhibiting the quantitatively enhanced level of protein expression conferred by the tat/HIV element. It produced a biologically significant TNF inhibition that was at least as strong as that achieved using a CMV promoter-driven sTNFR:Ig construct. There was a dose- and time-dependent relationship between the pro-inflammatory cytokine used, and the generation of TNF antagonist activity by SAA2-tat/HIV-sTNFR:Ig. Although sTNFR:Ig protein can be induced by either TNF-alpha or interleukin (IL)-1beta, its antagonist activity is limited to the former cytokine. The SAA2-tat/HIV-sTNFR:Ig construct, and derivatives thereof, may therefore be ideally suited to gene therapy applications that require the local production of potent and specific immune modifiers only when there is active pathology. It may consequently be of particular use in the future treatment of diseases such as rheumatoid arthritis.

Increased prevalences of epidermal and hepatobiliary neoplasms in white suckers (Catostomu commersoni) and brown bullheads (Ictalurus nebulosus) in the Western region of Lake Ontario have been associated with industrial pollution, but the identity and causative role of environmental carcinogens have not yet been established. Most epidermal tumors of lip and body skin are benign focal proliferations that occur in fish from the polluted Hamilton region, and also in fish from less polluted sites in the Great Lakes. These skin tumors in white suckers do not have consistent alterations in cellular glutathione S-transferases (GST), suggesting that growth of skin tumors is not promoted by chemicals normally detoxified by GST. However, elevated levels of glutathione peroxidase (GPO) and glutathione reductase (GR) in skin papillomas are indicative of promotional peroxidative tissue injury, either caused directly by xenobiotics or indirectly by chemical-induced inflammation. Liver tumors in white suckers from Lake Ontario include preneoplastic, benign, and malignant populations of hepatocellular and biliary cells, all of which are more prevalent in fish from polluted sites. These liver tumors are consistently associated with chronic cholangiohepatitis and segmental cholangiofibrosis, but these conditions also occur in white suckers in non-industrial locations. Thus, the natural occurrence of biliary disease, not attributable to industrial pollution, may have some influence on the development of liver tumors. Some preneoplastic lesions and the majority of neoplastic hepatocellular and biliary lesions in white suckers have low levels of total GST, indicating that these liver neoplasms are not promoted by xenobiotics normally detoxified by hepatic GSTs.(ABSTRACT TRUNCATED AT 250 WORDS)