Amphotericin B in children with malignant disease: a comparison of the toxicities and pharmacokinetics of amphotericin B administered in dextrose versus lipid emulsion.

In a prospective, randomized clinical trial, the toxicity of 1 mg of amphotericin B (AmB) per kg of body weight per day infused in 5% dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease. In an analysis of 82 children who received a full course of 6 days or more of AmB (117 courses), it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion, with there being no difference between the two methods of AmB administration. An intent-to-treat comparison of the numbers of courses affected by acute toxicity (fever, rigors) and chronic toxicity (nephrotoxicity) also indicated that there was no significant difference between AmB infused in dextrose (78 courses) and AmB infused in lipid emulsion (84 courses).

Fetal oxygen saturation monitoring in labour: an analysis of 118 cases.

Fetal oxygen saturation (FSpO2) was recorded during labour to determine the relationship between FSpO2 and indicators of fetal well-being, including umbilical blood gases, xanthine (X), hypoxanthine (Hx) and Apgar scores. This is one of the largest reported series of fetal pulse oximetry, with 118 fetuses monitored for over 329 hours. Mean FSpO2 for all cases was 46.

Plasma and serum micronutrient concentrations in preschool children.

The plasma concentrations of vitamin A, vitamin E, beta-carotene and serum concentrations of zinc, retinol-binding protein and prealbumin were examined for a random cluster sample, stratified by socioeconomic status, of 467 healthy preschool children. Children were aged 9-62 months; 44% were females. The mean plasma values were: vitamin A, 1.

Age-specific reference intervals for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin for Sydney children aged 9-62 months.

Paediatric reference intervals for blood concentrations of certain nutrients are often based on either adult data or are derived from small samples of young children. Biochemical data were obtained from 467 randomly selected, healthy preschool children aged 9-62 months in Sydney, Australia. Data were obtained for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin.

Effect of mu, delta and kappa opioid receptor agonists on a reactive oxygen species mediated model of skin inflammation.

Opioid agents have been shown to protect against tissue damage caused by hypoxia/reperfusion, an event which has a significant reactive-oxygen-species (ROS) involvement. We have investigated the potential anti-inflammatory activity of three opioid agonists, DAMGO, DPDPE and U50488 in rat skin inflammation induced by the ROS hydrogen peroxide. The model involves the intradermal injection of the enzyme glucose oxidase which converts glucose to D-gluconic acid and H2O2 which is locally released.

Reactive oxygen species and iron--a dangerous partnership in inflammation.

Cells of nearly all forms of life require well-defined amounts of iron for survival, replication and expression of differentiated processes. It has a central role in erythropoiesis but is also involved in many other intracellular processes in the tissues of the body. It is the fourth most abundant element in the Earth's crust and the most abundant transition metal in living organisms for which its characteristic chemistry endows it with a series of properties enabling it to fulfil certain biological reactions especially those involving redox mechanisms.

Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia.

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.

Vitamin A status in preterm neonates with and without chronic lung disease.

It has been proposed that there is an association between vitamin A (VA) deficiency and the development of chronic lung disease (CLD) in preterm infants. This study was designed to measure the VA status in preterm infants and to compare the results in the group of babies who developed CLD with the group who did not. Vitamin A status was assessed by measuring plasma VA, retinol binding protein (RBP) and the plasma VA:RBP molar ratio in 25 infants of less than 31 weeks gestation during the first 28 days of life.

Determination of conjugated and unconjugated serum 3 alpha-OH bile acids by high-performance liquid chromatography.

A simple reverse-phase liquid chromatographic method has been developed for the quantitative measurement of 11 3 alpha-OH bile acids in paediatric serum samples. Bile acids are enzymatically reduced to the corresponding 3-keto compound and then derivatized with the fluorophore dansyl hydrazine. Preliminary fractionation of bile acids is not required.

Mystery of the poisoned expedition.

The Burke and Wills expedition through the interior of Australia in the nineteenth century ended in calamity. But the cause of death was more pernicious than anyone at the time had imagined: beriberi due to thiaminase poisoning.

Proinflammatory effects of morphine in the rat adjuvant arthritis model.

Morphine has been shown to alter various aspects of the immune response. We examined its effect on progression of the T-cell-mediated model, rat adjuvant arthritis. Saline, morphine or the opioid antagonist naloxone were administered to male Wistar rats via subcutaneous osmotic pumps implanted three days prior to adjuvant disease induction by an intra-dermal injection of Mycobacterium tuberculosis in oil.

N-Trifluoroacetyl-ethanolamine: a proposed urinary metabolite of halothane: validation and measurement in children.

It has been postulated that trifluoroacetyl chloride, a halothane metabolite, can bind covalently with the phosphatidylethanolamine component of the hepatic cell membrane and cause cell necrosis. Breakdown of the necrotic hepatocyte would release N-trifluoroacetyl-ethanolamine (TFAE) into the serum with subsequent urinary excretion. An original High Performance Liquid Chromatography (HPLC) method for the measurement of TFAE is described.

Biliary excretion of the halothane metabolite trifluoroacetic acid in infants.

In humans the biliary excretion of trifluoroacetic acid, the major halothane metabolite, has not been studied. We investigated the biliary excretion of trifluoroacetic acid in two infants aged five months and two months following halothane anaesthesia for the operation of choledocholithotomy. Bile, urine and faeces were collected continuously for five days after operation and trifluoroacetic acid excretion measured.

Halothane in children with chronic liver disease.

Exacerbation of pre-existing liver disease after halothane anaesthesia has been reported in adult patients. A prospective study was performed in 38 children with biopsy-proven liver disease to assess the effect of surgery and halothane anaesthesia on liver function. Plasma liver enzyme levels were measured immediately preoperatively and again four to eight days after surgery and halothane anaesthesia.

Quality assurance for biogenic amines with authentic patient specimens.

The measurement of biogenic amines and metabolites is essential for diagnosis and follow-up of neural crest tumors. A Quality Assurance programme involving the distribution of urine specimens obtained from patients with neural crest and related tumors was conducted by the Australian Association of Clinical Biochemists' Working Party on Biogenic Amines in 1988. Fifty laboratories participated in the programme and measured a number of analytes with a variety of methods.

Successful treatment of dihydropteridine reductase deficiency, with an interesting effect of 5-hydroxytryptophan deficiency on sleep patterns.

We report a child in whom dihydropteridine reductase deficiency was diagnosed prenatally because of an affected sibling and who was treated from birth with apparent good response. This family has been reported before (Firgaira et al., 1980, 1981, 1983; Lipson et al.

Determination of individual bile acids in serum by high performance liquid chromatography.

A high performance liquid chromatographic (HPLC) method for analysis of 4 free and 8 conjugated bile acids in submicromolar quantities in serum is described using precolumn derivatization with 4-bromomethyl-7-methoxycoumarin (BMC) and fluorescence detection. Bile acids were extracted from serum with 0.4 M sodium bicarbonate, adsorbed onto a Sep-Pak C18 cartridge and eluted with methanol.

Halothane metabolism in children.

Halothane (1% v/v inspired) was administered for 60 min to six children of mean age 74 months (range 14-119 months). Uptake of halothane was measured from the difference in the concentration in inspired and expired gas and varied from 176 to 310 mg kg-1, depending on minute ventilation. After administration of halothane ceased, its elimination in expired gas was measured in four patients until the conclusion of anaesthesia; 32-37% of the absorbed halothane was expired 90 min after halothane administration ceased.

A urinary cysteine-halothane metabolite: validation and measurement in children.

An attempt was made in children to identify a urinary halothane-cysteine conjugate which had been described previously in adult patients following administration of halothane. If this conjugate was found it would indicate that a reductive metabolite of halothane binds covalently with the sulphydryl-containing amino acid, cysteine, a reaction which could lead to hepatic injury. The potential halothane-cysteine conjugate, N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (acetyl BCFEC), was prepared and the identity of the compound established using hydrogen-1 and carbon-13 NMR spectroscopy and methane chemical ionization mass spectrometry.

Occurrence of platelet-activating factor (PAF) and an endogenous inhibitor of platelet aggregation in diffuse cutaneous mastocytosis.

We have identified PAF in the blister fluid from a patient with bullous mastocytosis, a rare form of mast-cell disease. We have found a novel endogenous inhibitor of platelet aggregation which obscured the presence of the PAF in unprocessed blister fluid and in ethanol or lipid extracts. The PAF was characterized by the demonstration of chromatographic, mass spectral and biological properties identical to those of authentic PAF.

A field study report of intensive computer keyboard training with schoolchildren.

A video-based keyboard skills training programme was used to teach primary and secondary school students to touch type, in ten 45-min lessons. Previous research (Glencross and Bluhm, 1986) had found the programme to be successful in training a variety of personnel in the workforce. In all, 197 students (105 females, 92 males) received instruction over a two-week period.