Quality in the analytical phase

In today\u27s health care system the prevalence of medical errors seems to be high as stated by the report of the Institute of Medicine (IOM). An error rate of about 10% in clinical medical laboratories has been consistently reported in the literature. Most of these errors occur in the pre-analytical phase. Because only a small number of errors will be seen in the analytical phase, it is very likely that these might be very often ignored. This overview will deal with the requirements of quality that is not based on quality control sample measurement only. The knowledge of analytical interferences and critical sample quality will offer valuable solutions to improve the global quality of the total testing process. Some special areas of the analytical process such as calibration, quality control, reference interval, drug interference, statistical analysis, paraproteins and volume displacement effect will be discussed. With some examples from the literature and personal investigation, the impact of errors in the analytical process will be better understood and the examples will help reducing the number of analytical errors and interferences, so that a much better patient safety can be granted

Evaluation of reverse phase protein array (RPPA)-based pathway-activation profiling in 84 non-small cell lung cancer (NSCLC) cell lines as platform for cancer proteomics and biomarker discovery

AbstractThe reverse phase protein array (RPPA) approach was employed for a quantitative analysis of 71 cancer-relevant proteins and phosphoproteins in 84 non-small cell lung cancer (NSCLC) cell lines and by monitoring the activation state of selected receptor tyrosine kinases, PI3K/AKT and MEK/ERK1/2 signaling, cell cycle control, apoptosis, and DNA damage. Additional information on NSCLC cell lines such as that of transcriptomic data, genomic aberrations, and drug sensitivity was analyzed in the context of proteomic data using supervised and non-supervised approaches for data analysis. First, the unsupervised analysis of proteomic data indicated that proteins clustering closely together reflect well-known signaling modules, e.g. PI3K/AKT- and RAS/RAF/ERK-signaling, cell cycle regulation, and apoptosis. However, mutations of EGFR, ERBB2, RAF, RAS, TP53, and PI3K were found dispersed across different signaling pathway clusters. Merely cell lines with an amplification of EGFR and/or ERBB2 clustered closely together on the proteomic, but not on the transcriptomic level. Secondly, supervised data analysis revealed that sensitivity towards anti-EGFR drugs generally correlated better with high level EGFR phosphorylation than with EGFR abundance itself. High level phosphorylation of RB and high abundance of AURKA were identified as candidates that can potentially predict sensitivity towards the aurora kinase inhibitor VX680. Examples shown demonstrate that the RPPA approach presents a useful platform for targeted proteomics with high potential for biomarker discovery. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge

Dry chemistry : analysis with carrier-bound reagents /

Enlarged transl. of the German edition, Thieme, Stuttgart, 198

Diversity of layer 5 projection neurons in the mouse motor cortex

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function

Response to Tony Badrick regarding "Letter to the Editor regarding the article by Wayne J. Dimech et al. Time to address quality control processes applied to antibody testing for infectious diseases. Clin Chem Lab Med 2023; 61(2): 205-212 by"

Response to Tony Badrick regarding "Letter to the Editor regarding the article by Wayne J. Dimech et al. Time to address quality control processes applied to antibody testing for infectious diseases

Time to address quality control processes applied to antibody testing for infectious diseases

As testing for infectious diseases moves from manual, biological testing such as complement fixation to high throughput automated autoanalyzer, the methods for controlling these assays have also changed to reflect those used in clinical chemistry. However, there are many differences between infectious disease serology and clinical chemistry testing, and these differences have not been considered when applying traditional quality control methods to serology. Infectious disease serology, which is highly regulated, detects antibodies of varying classes and to multiple and different antigens that change according to the organisms' genotype/serotype and stage of disease. Although the tests report a numerical value (usually signal to cut-off), they are not measuring an amount of antibodies, but the intensity of binding within the test system. All serology assays experience lot-to-lot variation, making the use of quality control methods used in clinical chemistry inappropriate. In many jurisdictions, the use of the manufacturer-provided kit controls is mandatory to validate the test run. Use of third-party controls, which are highly recommended by ISO 15189 and the World Health Organization, must be manufactured in a manner whereby they have minimal lot-to-lot variation and at a level where they detect exceptional variation. This paper outlines the differences between clinical chemistry and infectious disease serology and offers a range of recommendations when addressing the quality control of infectious disease serology

Standard-Arbeitsanleitung zur peripher venösen Blutentnahme für die labormedizinische Diagnostik

Für die Gewinnung von Blut für die Diagnostik ist die periphere venöse Blutentnahme das häufigste Vorgehen. Eine fehlerhafte Blutentnahme ist eine relevante Quelle fehlerhafter Befunde. Aus diesem Grund werden als Anleitung für die Abnehmenden die wichtigen Schritte praxisnah detailliert beschrieben. Zu den dargestellten Schritten zählen Verantwortlichkeiten, klinische Fragestellung und Testauswahl, Vorbereitung und Identifikation des Patienten, Durchführung der Entnahme und Probentransport

Standard operating procedure for peripheral venous blood sampling

This document provides a recommendation for peripheral venous blood sampling by the working group Extraanalytical Quality of the German, Austrian and Swiss Society for Clinical Chemistry and Laboratory Medicine (DGKL, OGLMKC and SGKC/SSCC). It provides guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure for healthcare staff members in German-speaking countries