Editorial: Opportunistic infections due to Aspergillus

Changes in plasma thyroxine (T4) concentrations were followed in 27 fetal sheep after surgical implantation of catheters. Fourteen days were required before stable concentrations of T4 were achieved, whether surgery was performed between 90 and 96 days or 109 and 120 days gestation. Twenty-three fetuses were followed to birth, and during the last four days the T4 concentrations showed no change in 11 fetuses and a significant decrease in the other 12. Birth occurred between 142 and 157 days gestation in both groups. There was a significant rise in T4 concentration during labour in all 23 fetuses. There were large differences among the plasma T4 concentrations of individual ewes which were not related to ambient temperature.     

The effect of dyshemoglobins on pulse oximetry: Part I, Theoretical approach and Part II, Experimental results using an in vitro test system

Pulse oximeters are known to be inaccurate in the presence of elevated concentrations of carboxyhemoglobin and methemoglobin. This paper attempts to alleviate some of the confusion that exists between fractional and functional saturation, and to clarify the comparison of each with SpO2. A series of theoretical relationships between pulse oximeter reading (SpO2) and actual oxygen saturation (both fractional and functional) is derived using simple absorption theory. The theoretical relationships are checked using an experimental in vitro test system. This consists of a blood circuit containing a model finger, capable of simulating the pulsatile transmission signals through a real finger. Theoretical predictions and experimental results are compared and are found to agree well in the presence of carboxyhemoglobin, but less well with methemoglobin. Possible reasons are discussed.     

Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters

After administration of CTP-11, a camptothecin derivative exhibiting a wide spectrum of antitumor activity, dose-limiting gastrointestinal toxicity with great interpatient variability is observed. Because the biliary excretion is a major elimination pathway for CPT-11 and its metabolites [an active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), and its glucuronide, SN38-Glu], several hypotheses for the toxicity involve biliary excretion. Here, we investigated whether primary active transport is involved in the biliary excretion of anionic forms of CPT-11 and its metabolites in humans using bile canalicular membrane vesicles (cMVs). Uptake of the carboxylate form of CPT-11 and the carboxylate and lactone forms of SN38-Glu by cMVs prepared from five human liver samples was ATP dependent. The concentration dependence of the ATP-dependent uptake of the carboxylate form of CPT-11 and SN38-Glu suggests the involvement of at least two saturable transport components, both with lower affinity and higher capacity than in rats. The ATP-dependent uptake of the carboxylate form of SN-38 showed a single saturable component but was detectable only in one human cMV sample. Both carboxylate and lactone forms of SN38-Glu uptake also showed a large intersample variability, although the variability was less than that observed for the carboxylate form of SN-38. On the other hand, the carboxylate form of CPT-11 exhibited much less variability. The carboxylate forms of SN38-Glu and SN-38 almost completely inhibited the ATP-dependent uptake of leukotriene C4, a well-known substrate of canalicular multispecific organic anion transporter, whereas the inhibition by the carboxylate form of CPT-11 was not as marked. Thus, multiple primary active transport systems are responsible for the biliary excretion of CPT-11 and its metabolites, and the major transport system for CPT-11 differs from that for the other two compounds. A greater degree of inter-cMV variability in the uptake of SN-38 and SN38-Glu may imply that interindividual variability in biliary excretion of these metabolites might contribute to interpatient variability in the toxicity caused by CPT-11.