Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.     

Neuropharmacological characterization of 1-aminocyclopropane-1-carboxylate and 1-aminocyclobutane-1-carboxylate, ligands of the N-methyl-D-aspartate-associated glycine receptor

Following intravenous administration, 1-aminocyclobutane-1-carboxylate (ACBC, 100 mg/kg), a N-methyl-D-aspartate (NMDA)-associated glycine receptor antagonist, was eliminated with a T1/2 of 5 min in mouse brain and 4 min in rat cerebrospinal fluid (CSF). 1-Aminocyclopropane-1-carboxylate (ACC), a NMDA-associated glycine receptor agonist, was found to have a T1/2 of less than 5 min in mouse brain. ACC and ACBC did not alter basal cerebellar cGMP. Glycine and D-serine increased cGMP, and 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a glycine antagonist, reversed the D-serine-induced increases in cGMP. In contrast, ACBC did not reverse the D-serine-induced increases in cGMP. These data suggest that despite their brain bioavailability and marked potency at the glycine receptor in vitro, ACC and ACBC are rapidly inactivated and thus have limited in vivo utility.     

Phylogenetic analysis of rhinovirus isolates collected during successive epidemic seasons

Human rhinoviruses (HRV) have been shown to be the major causative agent for mild respiratory infections, but also associated with more serious diseases, such as acute otitis media and pneumonia in children, and asthma. Despite the economical and medical importance of HRV, little is known about the circulation and genetic diversity of HRV during a given season. The aim of this study was to genetically characterize HRV strains causing acute respiratory infections in a cohort of small children during a 2 years follow-up time. Genetic relationships between 61 HRV field isolates were studied using partial genomic sequencing in the VP4/VP2 region (420 nt) and phylogenetic analysis of these sequences. Sequences from the clinical isolates clustered in the two previously known phylogenetic clades, the designated genetic group 2 (including HRV 14) being more predominant. The maximum genetic variation within group 1 was 32.3% and within group 2 it was 32.7%. Several distinct clusters could be observed, some of which were strictly seasonal, whereas some other variants were detected during several seasons. The results of this study show striking genetic diversity of the HRV strains circulating in a given community during a short time.     

Polypeptide chain termination in Saccharomyces cerevisiae

Summary The study of translational termination in yeast has been approached largely through the identification of a range of mutations which either increase or decrease the efficiency of stop-codon recognition. Subsequent cloning of the genes encoding these factors has identified a number of proteins important for maintaining the fidelity of termination, including at least three ribosomal proteins (S5, S13, S28). Other non-ribosomal proteins have been identified by mutations which produce gross termination-accuracy defects, namely the SUP35 and SUP45 gene products which have closely-related higher eukaryote homologues (GST1-h and SUP45-h respectively) and which can complement the corresponding defective yeast proteins, implying that the yeast ribosome may be a good model for the termination apparatus existing in higher translation systems.While the yeast mitochondrial release factor has been cloned (Pel et al. 1992), the corresponding cytosolic RF has not yet been identified. It seems likely, however, that the identification of the gene encoding eRF could be achieved using a multicopy antisuppressor screen such as that employed to clone the E. coli prfA gene (Weiss et al. 1984). Identification of the yeast eRF and an investigation of its interaction with other components of the yeast translational machinery will no doubt further the definition of the translational termination process.While a large number of mutations have been isolated in which the efficiency of termination-codon recognition is impaired, it seems probable that a proportion of mutations within this class will comprise those where the accuracy of A site codon-anticodon interaction is compromised: such defects would also have an effect on termination-codon suppression, allowing mis- or non-cognate tRNAs to bind stop-condons, causing nonsense suppression. The remainder of mutatoons affecting termination fidelity should represent mutations in genes coding for components of the termination apparatus, including the eRF: these mutations reduce the efficiency of termination, allowing nonsense suppression by low-efficiency natural suppressor tRNAs. Elucidation of the mechanism of termination in yeast will require discrimination between these two classes of mutations, thus allowing definition of termination-specific gene products.     

Foreign medical graduates and U.S. physician supply: old issues and new questions

Recent increases in the number of foreign medical graduates (FMGs) in U.S. hospital-training positions raise new questions about the future role of FMGs in U.S. medicine. Despite an historical surplus of physicians, forces such as greater demand for resident house officers, stabilization in undergraduate medical education enrollment, increase in demand for medical services, growth in both the number of women in medicine and physician employment in group practices, and continuing imbalances in the distribution of physicians favor FMG migration to the United States. Health system reform must be sensitive to the historical, current, and future role FMGs play in medical care delivery, especially in regard to service in underserved areas, specialties, and employment settings.     

Components of the costs of controlling quality: a transaction cost economics approach

This article identifies the components that contribute to a healthcare organization's costs in controlling quality. A central tenet of our argument is that at its core, quality is the result of a series of transactions among members of a diverse network. Transaction cost economics is applied internally to analyze intraorganizational transactions that contribute to quality control, and questions for future research are posed.