Amphotericin B serum levels in pediatric bone marrow transplant recipients

We studied amphotericin B (AMB) serum levels (n = 590) in 41 pediatric patients, who underwent allogeneic (21) or autologous (20) bone marrow transplantation (BMT). All patients received AMB orally as part of a total gut decontamination; 30/41 patients (73%) had AMB i.v. either for prophylaxis or therapy of fungal infections. Rapid initial dose escalation of AMB and the infusion over 1 h only were well tolerated by the children. Serum level monitoring allowed AMB long-term treatment safely to be administered in children suffering from transplantation-related complications (veno-occlusive disease of the liver, graft-versus-host disease of the liver). An h.p.l.c. method was used for monitoring AMB serum trough levels to avoid levels exceeding 2 mg/l. One lethal fungal infection was observed in 41 pediatric BMT recipients (2.4%). Rapidly increasing doses of AMB at start of therapy and drug monitoring by h.p.l.c. might help to reduce fungal mortality and renal toxicity by a dose sparing effect in BMT recipients.     

Effects of chronic ethanol consumption and pair feeding on rates of protein synthesis and nucleic acid composition in rat tibia.

An investigation was made into the chronic effects of ethanol feeding on bone (represented by the tibia). Treated rats were fed a liquid diet containing ethanol as 36% of total calories, and controls were pair-fed identical amounts of the same diet in which ethanol was substituted by isocaloric glucose. Bone DNA and RNA contents in ethanol-fed rats were not significantly different from glucose-fed controls at days 3, 7, 14, 28 and 42 of treatment. Fractional rates of bone protein synthesis were measured with [43H]-phenylalanine. At 3, 7, 14, 28 and 42 days, ethanol feeding had no effect on free and protein-bound specific radioactivities, nor on fractional or absolute rates of protein synthesis. Synthesis rates relative to RNA (RNA activities) and DNA (cellular efficiencies) were also not significantly altered by ethanol feeding at these time points. Comparisons were made between rats fed a standard solid laboratory diet ad libitum (i.e. normal rats), and those fed restricted amounts of glucose-containing liquid diet (i.e. dietary-restricted rats) for 42 days. In normal rats, there was an increase in tibial mass and accretion of total collagen content, but in dietary-restricted rats, this accretion was markedly impaired. Furthermore, whilst RNA and DNA contents were increased in tibia of normal rats, the contents of these nucleic acids were reduced in bones of dietary restricted rats. Fractional rates of bone protein synthesis in normal rats were unaltered after 42 days, but reduced by feeding the control liquid diet in restricted amounts.(ABSTRACT TRUNCATED AT 250 WORDS)     

NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Meniscal abnormalities: prospective correlation of double-contrast arthrography and arthroscopy

In a prospective study conducted over a 12-month period, 30 patients underwent double-contrast arthrography of the knee followed by arthroscopic study. An 80% correlation rate was found between results. Arthrography had a higher rate of accuracy (93%) than arthroscopy (84%) and had a 7% false-positive and 0% false-negative rate. A commonly overlooked arthrographic sign--the triple-S or stuck sail sign--was 91% accurate in the prediction of meniscal tears. The complementary nature of the two examinations is discussed.     

The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice

Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.