27:T519,

The anti-proliferative effects of natural cytokines, human tumour necrosis factor-β, natural human interferon-α and natural human interferon-γ, on three human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were investigated in vitro. The anti-proliferative effect was determined using the dye uptake method and analysed for synergism by the median effect principle. Tumour necrosis factor-β, as a single agent, had little anti-proliferative effect on any of the three cell lines, whereas interferon-α and interferon-γ exhibited a strong anti-proliferative effect against two cell lines (MIA PaCa-2 and BxPC-3) and one cell line (BxPC-3), respectively. When tumour necrosis factor-β and interferon-α were administered together (ratio 1:1), a synergistic effect was observed against PANC-1 cells. The combination of tumour necrosis factor-β and interferon-γ (ratio 10:1) was synergisic against both PANC-1 and MIA PaCa-2 cells. A synergistic anti-proliferative effect of tumour necrosis factor-β and interferons was, therefore, observed even for cell lines that showed little biological response to each cytokine alone. The data suggest that some future improvement in the treatment of pancreatic cancer may be obtained by using combination cytokine therapy.

28:T521,

The efficacy of intravenous mexiletine in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation was studied in 30 normotensive patients undergoing elective surgery. The patients were randomly allocated to one of three treatment groups: saline (n = 10); 2 mg/kg mexiletine (n = 10); and 3 mg/kg mexiletine (n = 10). The placebo/mexiletine was administered immediately before induction of anaesthesia using 5 mg/kg thiopentone and tracheal intubation was facilitated with 0.2 mg/kg vecuronium; laryngoscopy lasting 30 s was attempted 2 min after induction of anaesthesia. All groups showed a significant (P < 0.05) increase in mean arterial pressure and heart rate associated with tracheal intubation. The increase in mean arterial pressure was significantly (P < 0.05) smaller in patients receiving 3 mg/kg mexiletine compared with those receiving either saline or 2 mg/kg mexiletine. There was no significant attenuation in heart rate in either of the mexiletine treatment groups compared with the saline group. It is concluded that 3 mg/kg mexiletine given intravenously provides a simple and effective method for attenuating the pressor response to laryngoscopy and tracheal intubation.

29:T4ec,

The clinical significance of combining local anaesthetics with dextran is controversial. Although a number of investigators have found that dextran can prolong the action of local anaesthetics, others have not been able to demonstrate any significant change in the duration of anaesthesia. A study was carried out to investigate the effect of dextran on the pharmacokinetic behaviour of lignocaine during epidural anaesthesia in 20 adult male patients, who were randomly allocated to two treatment groups: group 1 (n = 10) was given lignocaine – dextran; group 2 (n = 10) was given lignocaine – saline. The results of the study demonstrated that the addition of dextran to epidural lignocaine significantly slowed systemic absorption of lignocaine as indicated by a smaller absorption rate constant, a reduced peak plasma concentration (C_max), a delayed time to reach Cmax, and a smaller area under the concentration – time curve. The observed findings suggest that dextran reduces vascular uptake of lignocaine from epidural space and that it may prolong the duration of action. The significance of these findings on systemic toxicity, dosage and onset of action of lignocaine need to be investigated.

2a:T93c,