Background: The serum or plasma total bilirubin concentration (B(T)) has long been the standard clinical laboratory test for evaluating neonatal jaundice, despite studies showing that B(T) correlates poorly with acute bilirubin encephalopathy (ABE) and its sequelae including death, classical kernicterus, or bilirubin-induced neurological dysfunction (BIND). The poor correlation between B(T) and ABE is commonly attributed to the confounding effects of comorbidities such as hemolytic diseases, prematurity, asphyxia, or infection. Mounting evidence suggests, however, that B(T) inherently performs poorly because it is the plasma non-protein-bound (unbound or free) bilirubin concentration (B(f)), rather than B(T), that is more closely associated with central nervous system bilirubin concentrations and therefore ABE and its sequelae.
Content: This article reviews (a) the complex relationship between serum or plasma bilirubin measurements and ABE, (b) the history underlying the limited use of B(f) in the clinical setting, (c) the peroxidase method for measuring B(f) and technical and other issues involved in adapting the measurement to routine clinical use, (d) clinical experience using B(f) in the management of newborn jaundice, and (e) the value of B(f) measurements in research investigating bilirubin pathochemistry.
Summary: Increasing evidence from clinical studies, clinical experience, and basic research investigating bilirubin neurotoxicity supports efforts to incorporate B(f) expeditiously into the routine evaluation of newborn jaundice.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1373/clinchem.2008.121269 | DOI Listing |
Clin Infect Dis
January 2025
Professor of Medicine, Director, Institute for Therapeutic Innovation at University of Florida, Orlando, FL, USA.
Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM).
View Article and Find Full Text PDFCurr Opin Struct Biol
January 2025
Oxford Protein Informatics Group, Department of Statistics, University of Oxford, 24-29 St Giles', Oxford, OX1 3LB, United Kingdom.
Therapeutic antibodies are manufactured, stored and administered in the free state; this makes understanding the unbound form key to designing and improving development pipelines. Prediction of unbound antibodies is challenging, specifically modelling of the CDRH3 loop, where inaccuracies are potentially worse due to a bias in structural data towards antibody-antigen complexes. This class imbalance provides a challenge for deep learning models trained on this data, potentially limiting generalisation to unbound forms.
View Article and Find Full Text PDFThe clinical breakpoint for a drug-pathogen combination reflects the drug susceptibility of the pathogen wild-type population, the location of the infection, the integrity of the host immune response, and the drug-pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (CO), which is one of the three components used to establish the clinical breakpoint.
View Article and Find Full Text PDFBiotechnol J
January 2025
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China.
Salmonella is a common foodborne zoonotic pathogen that poses a great threat to human health and breeding industry. The rapid detection of Salmonella is necessary for early prevention and control. In this study, a subtractive inhibition assay (SIA) based on surface plasmon resonance (SPR) for the rapid detection of Salmonella was developed.
View Article and Find Full Text PDFDalton Trans
January 2025
School of Chemistry, UNSW Sydney, NSW 2052, Australia.
In my proposed mechanism of Mo-nitrogenase there are two roles for separate N molecules. One N diffuses into the reaction zone between Fe2 and Fe6 where a strategic gallery of H atoms can capture N to form the Fe-bound HNNH intermediate which is then progressively hydrogenated through intermediates containing HNNH, NH and NH entities and then two NH in sequence. The second N can be parked in an N-pocket about 3.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!