Observer-blinded comparison of two nonopioid analgesics for postoperative pain in piglets.

Piglets are popular for studies of respiratory and cardiovascular function, but opioid analgesics are contraindicated in these studies because of central nervous system depression. We evaluated two nonopioid analgesics for postoperative pain relief following implantation of a central arterial catheter via an inguinal incision. Animals were randomly assigned to paracetamol-treated (n=8, rectal suppositories, 100 mg/kg) meloxicam-treated (n=8, 1 mg/kg meloxicam via the catheter) or untreated control group (n=8, placebo suppositories and normal saline). Additional controls received paracetamol or meloxicam, without pain (n=6 for both groups). Behavioral and physiological assessments, and blood sampling were undertaken at nine timed intervals until 24 h after surgery. Multifactorial numerical rating scale (NRS), behavioral and physiological pain scores (PPS) decreased over time for all groups (P<.001). On NRS and behavioral criteria, meloxicam was significantly better than paracetamol (P<.001), and both were better than control (p<.001 for each). Physiological parameters discriminated between the control and analgesia-treated groups, but not between paracetamol and meloxicam. Preliminary pharmacokinetics, determined by isocratic high-performance liquid chromatography (HPLC), revealed no difference in the half-life of paracetamol (2.5+/-0.3 h) vs. meloxicam (3.4+/-0.4 h). Paracetamol and meloxicam provided effective postoperative analgesia in piglets, with meloxicam superior to paracetamol on behavioral criteria.

Determinants of acute regional toxicity following isolated limb perfusion for melanoma.

Hyperthermic isolated limb perfusion (ILP) with melphalan is well established as an effective form of treatment for recurrent melanoma confined to an extremity. High drug concentrations in the limb are readily achieved, without systemic side-effects. However, regional toxicity can lead to considerable morbidity and functional disturbance. This study was undertaken to evaluate factors which might contribute to acute regional toxicity following ILP. Melphalan concentrations in limb blood samples taken at regular intervals during 135 ILPs were measured by HPLC, allowing peak melphalan concentration and area under the curve (AUC) for each procedure to be determined. Acute regional toxicity associated with ILP was found to be significantly correlated with limb tissue temperatures > 40 degrees C, peak melphalan concentration and melphalan AUC, in decreasing order, but was not correlated with tourniquet time. Further studies are required to directly assess melphalan uptake by tumour tissue, and to relate this to both limb toxicity and tumour response.

Stability of cyclosporine in an extemporaneously compounded paste.

The stability of cyclosporine in an extemporaneously compounded paste was studied. Cyclosporine oral solution 100 mg/mL was mixed with an adhesive gel to prepare six aluminum-lined ointment tubes containing paste with cyclosporine 9.6 mg/g. Two of the tubes were stored at 37 degrees C, two at 21 degrees C, and two at 2 degrees C. Cyclosporine was extracted from samples taken on days 2, 4, 5, 7, 9, 14, 18, 22, 28, and 31, and the concentration was measured by high-performance liquid chromatography (except for samples obtained on day 2) and fluorescence polarization immunoassay. Throughout the study period, the concentration of cyclosporine remaining in the paste was > 90% of the initial concentration according to both assay methods. Cyclosporine 9.6 mg/g in a paste compounded extemporaneously from cyclosporine oral solution and an adhesive gel was stable for at least 31 days when stored in aluminum-lined ointment tubes at 37, 21, and 2 degrees C.

Elevated plasma vitamers of vitamin B6 in patients with chronic renal failure on regular haemodialysis.

Plasma pyridoxal-5'-phosphate (PL-5'-P), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) were measured by high-performance liquid chromatography (HPLC) in 39 patients (15 male, 24 female) with chronic fenal failure undergoing regular haemodialysis and 46 healthy controls (28 male, 18 female). All three vitamers of vitamin B6 and the metabolite were significantly elevated in the haemodialysis patients. Mean PL-5'-P and PN concentrations were 20 times the mean in controls. Only one patient took a vitamin B6 supplement. In view of the neurotoxicity of supranutritional intakes of PN in normal humans we suggest that supplements of PN be carefully monitored when administered to patients with chronic renal failure.

Vitamin supplementation of patients receiving haemodialysis.

In order to assess the necessity of vitamin supplementation for patients who are receiving haemodialysis, measurements of vitamin status were made, and both dietary and supplementary intakes were assessed, in 26 patients who were undergoing haemodialysis. Blood samples were collected from these patients before they underwent haemodialysis, after an overnight fast, for the measurement of plasma retinol, alpha-tocopherol and ascorbate levels. Serum and erythrocyte folate levels were measured also. Thiamin status was assessed by the effect of added thiamin pyrophosphate on erythrocyte transketolase activity and pyridoxine status was assessed by the effect of added pyridoxal-5'-phosphate on erythrocyte aminotransferase activity. All patients had elevated plasma retinol levels; 48% of patients had elevated plasma alpha-tocopherol levels; the plasma ascorbate level was low in 50% of patients but was elevated in 25% of patients; and plasma and erythrocyte folate levels were elevated in 76% and 91% of patients, respectively. Thiamin status was normal in all but one patient and the pyridoxine level appeared to be low in two other patients. Many patients had low dietary intakes of vitamin C, folate and vitamin B6. We conclude that supplements of vitamins A and E are not required and, when dietary intakes of water-soluble vitamins are marginal, these should be supplemented at a dose as near as possible to the recommended dietary intake.