A marked improvement has occurred in the survival of patients with cystic fibrosis with an FEV(1) less than 30% predicted. Secondary analyses suggest that some of this improvement may be due to use of recombinant human DNase.
Overall improvements in resources and organization are accompanied by reduced mortality, shorter admissions and greater access to specialist services. There remains, however, considerable variation in the quality of secondary care provided between units.
Background: Assays for cardiac troponin (cTn) have undergone improvements in sensitivity and precision in recent years. Increased rates of outliers, however, have been reported on various cTn platforms, typically giving irreproducible, falsely higher results. We aimed to evaluate the outlier rate occurring in patients with elevated cTnI using a contemporary and high-sensitivity assay. Methods: All patients with elevated cTnI (up to 300 ng/L) performed over a 21-month period were assayed in duplicate. A contemporary assay (Abbott STAT Troponin-I) was used for the first part of the study and subsequently a highsensitivity assay (Abbott STAT High-Sensitive Troponin-I) was used. Outliers exceeded a calculated critical difference (CD) (CD ¼ z ¡2  SD Analytical ) where z ¼ 3.5 (for probability of 0.0005) and critical outliers also were on a different side of the decision level. Results: The respective outlier and critical outlier rates were 0.22% and 0.10% for the contemporary assay (n ¼ 4009) and 0.18% and 0.13% for the high-sensitivity assay (n ¼ 3878). There was no significant reduction in outlier rate between the two assays ( 2 ¼ 0.034, P ¼ 0.854). Fifty-six percent of outliers occurred in samples where cTn was an 'add-on' test (and was stored and refrigerated prior to assay). Conclusion: Despite recent improvements in cTn methods, outliers (including critical outliers) still occur at a low rate in both a contemporary and high-sensitivity cTnI assay. Laboratory and clinical staff should be aware of this potential analytical error, particularly in samples with suboptimal sample handling such as add-on tests.
The yeast Kex2 protease is regarded as the prototype of the eukaryotic family of subtilisin-like serine proteases involved in processing after dibasic amino acid sequences. Here we investigate the specificity of Kex2 using recombinant human proalbumin variants. Proalbumins with the processing site sequences Arg-Arg and Lys-Arg were cleaved after the dibasic sequence at approximately the same rate by Kex2 in vitro, and yeast expressing either of these sequences secreted mature albumin into the culture medium. As expected, the Arg-Gly-Val-Phe-His-Arg-albumin (proalbumin Lille) was not a substrate for Kex2 and neither was the Arg-Gly-Arg-Phe-His-Arg-albumin. In contrast to the mammalian endoproteases furin and the hepatic proalbumin convertase, the Kex2 protease was adversely affected by a P4 arginine. There was an 85% decrease in the cleavage of Arg-Gly-Arg-Phe-Arg-Arg-albumin compared with normal; also chicken proalbumin with an Arg-Phe-Ala-Arg processing site sequence was not a substrate for Kex2. A P1' arginine had a marked negative effect on processing and N-terminal sequence analysis confirmed that cleavage was occurring at the P1-P1' bond. The sequence context surrounding the classical dibasic site is critical in determining susceptibility to cleavage by the Kex2 protease.
An elderly white man with a long history of psoriasis, previously treated with topical steroids and ultraviolet B (UVB), developed bullous pemphigoid shortly after starting psoralen plus UVA (PUVA) therapy. The eruption spread from the forearms to the arms and neck after phototherapy was discontinued. The clinical features of the 12 reported cases of PUVA‐induced bullous pemphigoid are reviewed.
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