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Drosophila melanogaster was used as a model system to explore the link between nutrition and immunity, and to investigate the role of nitric oxide (NO) in enhancing immunity following dietary enhancement with L-arginine. First, we show that adding L-arginine to the food medium increases the ability of D. melanogaster larvae to encapsulate the eggs of the parasitoid Asobara tabida. Secondly, we show that the increase in immunity is specific to L-arginine, and not to an enhanced calorific content, and that immunity decreases when larvae are fed food with added L-NAME, an inhibitor of nitric oxide synthase. Finally, we show that parasitised larvae fed L-arginine have increased haemocyte numbers, and that the lamellocytes (haemocytes which play a key role in encapsulation) show evidence of an increased production of NO. These results suggest that NO plays a key role in immunity and that the effect of NO is mostly targeted via the lamellocytes.

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BACKGROUND: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant. METHODS: The dose-dependent effects of adjuvant preoperative epidural tramadol on postoperative analgesia (pain scores and patient-controlled analgesia (PCA) use) and pain processing (heat pain thresholds) were prospectively studied in a double-blind, randomised, placebo-controlled 5-day trial. Forty patients undergoing knee or hip surgery received anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous PCA tramadol in all patients. RESULTS: Postoperative pain scores were similar in all groups. The time to first PCA use was shorter, the total dose and duration of PCA use greater, and side-effects more common with 20 mg tramadol than with 100 mg or placebo (P < 0.05). There were no differences in PCA doses required or side-effects between the tramadol 100 mg and placebo treatment groups. Heat pain tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively compared to baseline and placebo (P = 0.01). CONCLUSIONS: Preoperative adjuvant epidural tramadol does not improve postoperative analgesia after lidocaine epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti-analgesia and increased side-effects. While tramadol 100 mg depresses postoperative pain-processing, as measured by heat pain tolerance thresholds, this is not reflected in improved clinical pain measures.

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The postoperative combination of epidural sufentanil and epidural droperidol was assessed in 40 patients with hip or knee arthroplasties. Patients were given a single intravenous (i.v.) bolus of sufentanil 50 micrograms with either droperidol 2.5 mg or placebo (0.9% NaCl) epidurally in a double-blind, randomized design at the first request for postoperative analgesia. Pain scores, side effects, and sufentanil plasma concentrations were regularly assessed for 5 h after injection. Heat pain thresholds were measured pre- and postoperatively. The incidence of nausea, emesis, and pruritus associated with epidural sufentanil was decreased by epidural droperidol (P < 0.01, P < 0.001, P < 0.05, respectively). More patients were sedated with epidural droperidol than with placebo (P < 0.02). The initial reduction in pain scores was similarly profound, but the duration of analgesia after sufentanil and droperidol was significantly shorter than after sufentanil and placebo (P < 0.02). Phasic and tonic heat pain thresholds were increased postoperatively 1 h after sufentanil and placebo (P < 0.01 and P < 0.0005, respectively). Only the tonic heat pain thresholds were increased 1 h after sufentanil and droperidol (P < 0.002). The addition of epidural droperidol significantly reduced the excitatory side effects of epidural sufentanil while diminishing the duration of analgesia. These interactions may be of clinical significance in reducing the toxicity of opioids, but the effect on duration of analgesia must be considered when repeated doses of opioids are prescribed.

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Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient-controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (greater than 3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of difficult-to-treat patients.

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Epidural morphine is effective in the treatment of postoperative pain, but the incidence of associated side effects is high. To assess a potential reduction of opioid side effects by droperidol, 4 mg morphine with either placebo or 2.5 mg droperidol was injected epidurally in a double-blind, randomized, postoperative trial. Forty patients undergoing hip replacement surgery were studied. The overall incidence of side effects during the first 24 h in the group receiving droperidol and morphine was less than 50% of that in the group receiving placebo and morphine (P less than 0.008). Pruritus, emesis, nausea, urinary retention, and hypotension were diminished in the group with droperidol. No significant differences in duration or quality of analgesia were seen. Epidural injection of droperidol did not result in any local or systemic side effects.

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We carried out continuous direct pH measurements of gastric fluid in 49 female patients pretreated with 300 mg ranitidine by mouth on the evening prior to surgery and 150 mg by mouth before the operation. A further 51 women were pretreated with 30 ml sodium citrate shortly before admission to the operating room. Twenty patients received 30 ml sodium citrate via a separate gastric tube after the first pH measurement; 22 were given no premedication. In 95% of cases, 30 ml sodium citrate was found to increase the pH to over 3.5 within 5 min; a failure rate of 5% can therefore be expected. This can be explained mainly by the failure of sodium citrate to mix thoroughly with the gastric fluid. Pretreatment with ranitidine increased the pH to over 4.0 in every case, and the pH on extubation was still over 4.0 even after delayed pH on extubation was still over 4.0 even after delayed or prolonged operations. We recommend that 30 ml sodium citrate be given shortly before the beginning of emergency obstetric operations. However, we prefer ranitidine for elective operations in patients at risk for aspiration because it increases of the gastric fluid pH to at least 4.0 in every case.

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