Lars Ødum

Error tracking in a clinical biochemistry laboratory

Abstract Background: We report our results for the systematic recording of all errors in a standard clinical laboratory over a 1-year period. Methods: Recording was performed using a commercial database program. All individuals in the laboratory were allowed to report errors. The testing processes were classified according to function, and errors were classified as pre-analytical, analytical, post-analytical, or service-related, and then further divided into descriptive subgroups. Samples were taken from hospital wards (38.6%), outpatient clinics (25.7%), general practitioners (29.4%), and other hospitals. Results: A total of 1189 errors were reported in 1151 reports during the first year, corresponding to an error rate of 1 error for every 142 patients, or 1 per 1223 tests. The majority of events were due to human errors (82.6%), and only a few (4.3%) were the result of technical errors. Most of the errors (81%) were pre-analytical. Of the remainder, 10% were analytical, 8% were post-analytical, and 1% was service-related. Nearly half of the errors (n=550) occurred with samples received from general practitioners or clinical hospital wards. Identification errors were relatively common when non-technicians collected blood samples. Conclusions: Each clinical laboratory should record errors in a structured manner. A relation database is a useful tool for the recording and extraction of data, as the database can be structured to reflect the workflow at each individual laboratory. Clin Chem Lab Med 2009;47:1253–7.

Human protein HC (α1microglobulin) and inter-α-trypsin inhibitor in connective tissue

SummaryThe presence of protein HC-(α1-microglobulin) and inter-α-trypsin inhibitor was investigated in different human tissues. Inter-α-trypsin inhibitor is a complex protein composed of bikunin and two heavy polypeptide chains. Protein HC and bikunin are transcribed from a common gene. Inter-α-trypsin inhibitor immunoreactivity was detected in mast cells. The positive reaction could be blocked by antisera absorption with bikunin, indicating that mast cells contain only bikunin. Protein HC immunoreactivity was revealed on elastic fibres in connective tissue of skin, colon and lung, and on the internal elastic lamina of blood vessels. In the testis, the basement membrane of the seminiferous tubules reacted positively with protein HC antibodies.

Peptide Hormone Processing in Tumours: Biogenetic and Diagnostic Implications

Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotein structures. According to their structural organization and sequence homology, hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptide-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently, the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PIA), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.

An evaluation of the interference of hydroxycobalamin with chemistry and co-oximetry tests on nine commonly used instruments

Abstract The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0–1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.

Blood sampling for biochemical analysis from central venous catheters: Minimizing the volume of discarded blood

Abstract The purpose of the work was to establish a reliable procedure for blood sampling from central venous catheters with a minimal loss of blood. Based on previous studies of potassium measurements, the routine procedure had been to discard 12 ml of blood. In order to clear the catheter from substances from the infusion including potassium, the catheters were first flushed with 5 ml of saline. Repeated samples in fractions of 3 ml for hematological analyses (ethylenediaminetetraacetic acid plasma; seven patients), coagulation tests (citrate plasma; seven patients) and for serum measurements (eight patients) showed that a discarded volume of 3 ml corresponding to at least six times the dead-space of the catheters was sufficient after initial flushing with saline.

Pituitary adenylate cyclase activating polypeptide (PACAP) in human ovarian cancers

Synthesis of regulatory peptides has been described in a number of ovarian tumours. The recently isolated neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is expressed transiently in steroidogenic cells of normal rat ovary. In order to evaluate if ovarian tumours also synthesize PACAP, we investigated the expression and processing of pro-PACAP in 11 serous cystadenocarcinomas, one non-differentiated carcinoma, one borderline malignant and four adenomas. Using sequence specific radioimmunoassays and gel chromatography, we found that all tumours expressed PACAP-38 immunoreactivity. Ovarian cancers contained higher (P < 0.03) concentrations (median 0.9 pmol/g, range 0.5-1.6 pmol/g, n = 13) than benign tumours (median 0.5 pmol/g, range 0.4-0.6 pmol/g, n = 4). Chromatography showed that the tumours contained PACAP-38 and PACAP-31-38 suggesting a rather complete processing. By immunohistochemistry, few scattered PACAP positive cells in small clusters or as single cells were identified in the tumours.

Bikunin and alpha 1-microglobulin in human zona pellucida and connective tissue.

The occurrence of bikunin and ·1-microglobuli n was investigated in human ovary and Fallopian tubes. Bikunin and ·1-microglobulin are transcribed in the liver from a common gene. Bikunin immunoreactivity was detected in the zona pellucida. A positive reaction for bikunin was also observed in connective tissue of the oviduct. In addition, mast cells showed a more intense posi tive reaction than the surrounding connective tissue. Specific displaceable ·1-microglobulin immunoreactivity was revealed in the zona pellucida. The data suggest that bikunin and ·1- microglobulin are trapped in the zona pellucida.

Biosynthesis of inter-α-trypsin inhibitor and α1-microglobulin in a human hepatoma cell line

Abstract 1. 1. Biosynthesis of α1-microglobulin and inter-α-trypsin inhibitor was investigated in a human hepatoma cell line HepG-2. 2. 2. α1-Microglobulin was translated as a precursor common with the light chain of inter-α-trypsin inhibitor. 3. 3. α1-Microglobulin was synthesized and secreted into the growth medium within 30 min. 4. 4. Processing of inter-α-trypsin-inhibitor-related proteins appeared slow and incomplete. The light chain was connected via a chondroitinsulphate to a heavy chain to form a 125,000- Mr protein and secreted within 1–4 hr.

Characterization of urinary proteinase inhibitors with segments of amino acids sequences identical to sequences of pancreatic secretory trypsin inhibitor

1. Slow migrating proteinase inhibitors were isolated from pathological human urine. 2. The N-terminal amino acid sequence including 23 amino acids was identical to the one in pancreatic secretory trypsin inhibitor. 3. The slow migrating proteinase inhibitors occurred in 3 forms with different electrophoretic mobility. 4. Time of flight mass spectrometry showed that the Mw of one of the forms was 6241 while the Mw of another form was 5923. 5. The Ki of complexes with trypsin was determined to be 1 x 10(-10) M, with chymotrypsin and plasmin Ki was 1 x 10(-7) M. Elastase, kallikrein and thrombin were not inhibited.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in normal pregnancy but not in preeclampsia.

Abstract Background: Neutrophil gelatinase-associated lipocalin (NGAL) serum values have been shown to increase in preeclampsia. The goal of the present study was to evaluate changes in urinary NGAL concentrations during uncomplicated pregnancy and in cases of preeclampsia and hypertension. Methods: Fifty-one pregnant women who developed preeclampsia and 28 diagnosed with essential or gestational hypertension were investigated for urinary NGAL concentrations during pregnancy. As controls, 100 healthy pregnant women with uncomplicated singleton pregnancies were randomly selected. Urinary NGAL as well as urinary creatinine and albumin were measured by a standardized clinical chemistry platform (ARCHITECT®; Abbott Diagnostics, Abbott Park, IL, USA). Results: Urinary NGAL concentrations increased during pregnancy in healthy pregnant women, whereas this increase was not detected in preeclampsia. In order to correct for diuresis, spot urine concentrations were also determined as NGAL/creatinine ratio. NGAL/creatinine ratio in pregnancy week 36–38 was significantly lower in preeclampsia than in healthy pregnant women or pregnant women with hypertension. NGAL urinary concentrations did not correlate with albumin concentration in urine. Conclusions: Urinary NGAL is not a valuable early biomarker for preeclampsia.