Clinical Chemistry and Laboratory Medicine (CCLM)

Published by De Gruyter

Volume 40 Issue 10

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Contents
Journal Overview

June 1, 2005

The 9th Asian Pacific Congress of Clinical Biochemistry

P. Usha Sarma

Page range: 961-961

June 1, 2005

Circulating DNA in Plasma and Serum: Biology, Preanalytical Issues and Diagnostic Applications

Yanni Y. N. Lui, Y. M. Dennis Lo

Page range: 962-968

Abstract

The recent studies in circulating nucleic acids have brought about a new dimension to medical diagnostics. In oncology, various tumor-associated molecular alterations have been detected in the plasma/serum of cancer patients. These findings have important implications for the diagnosis, prognostication and monitoring of many types of malignancies. In pregnancy, the discovery of fetal DNA in maternal circulation has opened up a new source of fetal genetic material for noninvasive analysis for numerous fetal conditions and detection of certain pregnancy-associated disorders. The measurement of circulating DNA has also found potential application in the post-treatment monitoring of transplant patients and the assessment and prognostication of trauma patients. Although much attention has focused on circulating DNA, the knowledge of its biology is still at an early stage. For example, the origin and mechanisms of release of circulating DNA remain to be elucidated. The eventual clinical application of circulating DNA technology would also require the thorough elucidation of preanalytical factors that may affect its measurement in clinical laboratories.

June 1, 2005

Role of Steroid Hormones and Growth Factors in Breast Cancer

Leslie C. Lai

Page range: 969-974

Abstract

Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses.

June 1, 2005

Gene Polymorphism and Coronary Risk Factors in Indian Population

Tester F. Ashavaid, Kavita K. Shalia, Altaf A. Kondkar, Seema P. Todur, Kappiareth G. Nair, Sunita R. Nair

Page range: 975-985

Abstract

Asian Indians who have settled overseas and those in urban India have increased risk of coronary events. Reasons for this increased risk are thought to be genetic but are yet unclear. Advances in molecular cardiology have revealed a number of single nucleotide polymorphisms associated with atherosclerosis. In this review, gene polymorphisms that have been associated with coronary diseases among Indians are discussed. Topics include the genes involved in hyperlipidemia, hypertension, and homocysteine. Mutations in the low-density lipoprotein receptor ( LDLR ) gene resulting in familial hypercholesterolemia have strong association with premature atherosclerosis. Common polymorphism of the apolipoproteins (apo) B-100 and E genes have been associated with variation in lipid and lipoprotein levels. Recently identified polymorphisms in the apoC3 (T-455C, C-482T), and cholesteryl ester transfer protein (CETP) ( B1/B2 allele) genes are associated with increased triglycerides and reduced high-density lipoprotein (HDL)-levels, a feature now also common among Asian Indians. Angiotensin-converting enzyme-deletion (DD) polymorphism has been shown to influence beta-blocker therapy in heart failure. Mutations in methylenetetrahydrofolate reductase ( C667T ), cystathionine β-synthase ( T833C ), and methionine synthase ( A2756G ) genes cause hyperhomocysteinemia, an independent risk factor for atherothrombosis. As the genetics of atherosclerosis continues to evolve, these factors along with the newer emerging factors may become a part of the routine assessment, aiding prediction of future coronary events.

June 1, 2005

Clinical Utility of Free Drug Monitoring

Amitava Dasgupta

Page range: 986-993

Abstract

Most drugs are bound to serum proteins to a various degree. Only unbound or free drug is pharmacologically active. Usually total drug is measured for therapeutic monitoring because there is equilibrium between bound and free drugs, and concentration of free drug can be predicted from total drug concentration. However, under certain conditions this equilibrium is disturbed and the measured free drug concentration can be significantly higher than expected from total drug concentrations, especially for strongly protein-bound drugs. In such case a patient may experience drug toxicity even if the total drug concentration is within the therapeutic range. Conditions like uremia, liver disease and hypoalbuminemia can lead to significant increases in free drug concentration. Therefore, monitoring free phenytoin and free valproic acid is recommended in these patients. Drug-drug interactions can also lead to a disproportionate increase in free drug concentration. One strongly protein-bound drug can significantly displace another strongly proteinbound drug if both drugs share the same binding site. Several over-the-counter pain medications such as salicylate, naproxen, and ibuprofen can cause significant displacement of both phenytoin and valproic acid from albumin binding site. Interestingly, such interactions are absent in uremic patients. Elderly patients may have increased free phenytoin or valproic acid due to hypoalbuminemia. Elevated free phenytoin concentrations have also been reported in patients with AIDS. Although digoxin is 25% bound to protein, monitoring free digoxin is useful in patients with elevated endogenous digoxin-like immunoreactive substances or in patients overdosed with digoxin and being treated with digibind. Monitoring free digoxin can also eliminate interference of Chinese medicines Chan Su and Danshen in serum digoxin measurement by certain immunoassays. However, free drug monitoring is not a routine procedure in clinical laboratories due to technical difficulties and lack of established reference ranges for free drugs.

June 1, 2005

Telomerase – a Potential Molecular Marker of Lung and Cervical Cancer

Sudip Sen, Vijay G. Reddy, Randeep Guleria, Sunesh K. Jain, Kusum Kapila, Neeta Singh

Page range: 994-1001

Abstract

Telomerase, a ribonucleoprotein enzyme that adds hexameric TTAGGG nucleotide repeats onto telomeres is reactivated in most malignancies. Lung cancer is a common malignant disease worldwide as well as in India. Most patients present in advanced stages. As noninvasive diagnostic techniques are preferred, we assayed the telomerase activity in pre-bronchoscopy sputum and compared it with that of bronchial washings and bronchoscopic biopsies by telomeric repeat amplification protocol (TRAP) in 53 cases of lung cancer. These were corroborated with cytopathological/histopathological examinations. Telomerase activity was detected in 58.5% of sputum samples, 70% of bronchial washings and 74% of bronchoscopic biopsies thereby making it a good noninvasive diagnostic marker of lung cancer. Cervical cancer is the 7th most common cancer worldwide, with 100,000 new cases being reported annually in India. It is routinely screened by Papanicolaou's (Pap) smear. Human papilloma virus (HPV) is one of its etiological agents. We have assayed telomerase activity in relation to HPV-16/18 in cervical samples from 93 subjects ranging from normal to precancerous to frank cancers in tissue biopsies and cervical scrapings. HPV infection was detected by polymerase chain reaction (PCR) in 81% of tumor samples, in 6% of control hysterectomy samples and in 2% of cervical scrapings of normal healthy controls with HPV-16 being the predominant type. Telomerase activity was detected in 96.5% of cervical tumor samples, in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples, or in cervical scrapings of normal healthy controls. There was 71% correlation between telomerase activity and HPV-16/18 infection.

June 1, 2005

Association of Polymorphisms in the Collagen Region of Human SP-A1 and SP-A2 Genes with Pulmonary Tuberculosis in Indian Population

Taruna Madan, Shweta Saxena, Kolluri J. R. Murthy, Kambadur Muralidhar, Puranam Usha Sarma

Page range: 1002-1008

Abstract

Surfactant protein A (SP-A) binds to and modulates phagocytosis of Mycobacterium tuberculosis by macrophages. We investigated the relationship between polymorphisms in the collagen regions of SP-A1 and SP-A2 genes and pulmonary tuberculosis. In the present study, seven single nucleotide polymorphisms (SNPs) (4 exonic and 3 intronic) have been identified in the collagen regions of SP-A1 and SP-A2 genes in Indian population. Two intronic polymorphisms, SP-A1C1416T ((p = 0.0000, odds ratio (OR) = 20.767, 95% CI: 8.315<OR<51.870) and SP-A2C1382G (p = 0.0054; OR = 3.675, 95% CI: 1.400< OR<9.644), showed significant association with pulmonary tuberculosis (number of patients = 10, number of controls = 7). A redundant SNPA1660G of SP-A2 gene showed significant association with pulmonary tuberculosis (number of patients = 17, number of controls = 19, p = 0.0000, OR = 8.94, 95% CI: 3.31<OR<24.126). This polymorphism, when existing along with a non-redundant polymorphism, SP-A2G1649C (Ala91Pro) resulted in a stronger association with pulmonary tuberculosis (number of patients = 17, number of controls = 19, p = 0.000, OR = 16.3, 95% CI: 7.8644<OR<33.9244). The results indicated that these SNPs in the collagen region of SP-A2 may be one of the contributing factors to the genetic predisposition to pulmonary tuberculosis.

June 1, 2005

Effect of Hemodialysis on the Oxidative Stress and Antioxidants

Evrim Dursun, Tomris Ozben, Gültekin Süleymanlar, Belda Dursun, Gülsen Yakupoglu

Page range: 1009-1013

Abstract

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.

June 1, 2005

Total Iron Binding Capacity and Transferrin Concentration in the Assessment of Iron Status

Ishmael Kasvosve, Joris Delanghe

Page range: 1014-1018

Abstract

Transferrin concentration and total iron binding capacity (TIBC) are currently used to assess iron status. Although correlation between TIBC and transferrin is generally considered as good, conversion factors between the two analytes found in literature show large differences. Although the price per test is lower for TIBC, there are a number of analytical advantages of serum transferrin. Due to binding of iron to other plasma proteins (mainly albumin), TIBC methods generally overestimate the iron binding capacity of transferrin. Moreover, no generic reference values are available for TIBC. In contrast to TIBC, internationally accepted interim reference ranges are available for serum transferrin. The introduction of the international CRM 470 protein standard material has lead to a significant reduction in interlaboratory variation for transferring measurements. In view of these observations, determination of transferrin concentration, rather than TIBC, is recommended. However, in non-European populations characterized by a marked genetic variation in transferrin (TF BC and TF CD variants), in certain cases, immunochemical determination of transferrin may lead to errors. In these populations, TIBC measurements may be preferred.

June 1, 2005

Increased Levels of Osteoprotegerin in Hemodialysis Patients

Ivica Avbersek-Luznik, Ivan Malesic, Igor Rus, Janja Marc

Page range: 1019-1023

Abstract

Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a “decoy” receptor for receptor activator of NF-κB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and β-CrossLaps (CTx) were measured in a control group (n = 20, age 30±6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6±14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7±14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = −0.145, p = 0.593 and r = −0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.

June 1, 2005

Levels of Testosterone, Allopregnanolone and Homocysteine in Severe Hypothyroidism

Marie Bičíková, Jaroslava Tallová, Soňa Stanická, Martin Hill, Karel Vondra, Richard Hampl

Page range: 1024-1027

Abstract

Hypothyroidism is very often associated with cardiovascular diseases and neurological complications. Recently, homocysteine has been studied as an independent risk factor for atherosclerosis which negatively affects vascular endothelial cells. Because homocysteine metabolism is related to thyroid and steroid hormones, we studied these relationships in severe hypothyroidism and in euthyroid state. Homocysteine, testosterone and allopregnanolone concentrations were measured in the fasting plasma from 16 women who underwent total thyroidectomy, and who were either hypothyroid or euthyroid. Although all women used oral contraceptives, they were not protected against hyperhomocysteinemia during hypothyroid state. With the normalization of thyroid hormone concentrations homocysteine levels decreased to normal levels. There was a positive correlation between testosterone and homocysteine in the euthyroid state which suggests that not only estrogens but also androgen state should be considered in future studies on homocysteine.

June 1, 2005

The Levels of Serum Vitamin C, Malonyldialdehyde and Erythrocyte Reduced Glutathione in Chronic Obstructive Pulmonary Disease and in Healthy Smokers

Mukadder Çalikoğlu, Ali Ünlü, Lülüfer Tamer, Bahadir Ercan, Resul Buğdayci, Uğur Atik

Page range: 1028-1031

Abstract

There is an increasing interest in the concept that oxidant/antioxidant imbalance plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, most of the studies are concentrated on the local antioxidant/oxidant balance. In this study, we investigated the oxidant/antioxidant balance in systemic circulation of patients with COPD. Serum malonyldialdehyde (MDA), vitamin C and erythrocyte reduced glutathione (GSH) were determined in patients during acute exacerbation and during the stable phase of the disease, and compared with age-and sex-matched healthy controls. The levels of serum MDA, vitamin C and erythrocyte GSH were determined according to Yagi, Beutler and Bauer et al. , respectively. Serum MDA levels were significantly higher in patients compared to controls, and during acute exacerbation compared to the stable phase. MDA levels in patients with acute exacerbation and in those in stable phase were also higher than in controls. We found significantly decreased levels of erythrocyte GSH and serum vitamin C in patients with acute exacerbation and stable COPD compared to controls. Although smoking caused an increase in oxidative stress in controls, the measured parameters were not affected by smoking in the patient group. In conclusion, there is a systemic oxidant/antioxidant imbalance in COPD, and this imbalance is probably independent of smoking.

June 1, 2005

Highly Specific, Simple and Rapid Method for the Determination of Malondialdehyde in Blood Using High-Performance Liquid Chromatography

Kandár Roman, Mužáková Vladimíra, Čegan Alexander

Page range: 1032-1035

Abstract

A novel, highly specific, simple and rapid method for the determination of malondialdehyde (MDA), the routinely used marker for free radical generation in body fluids has been developed and evaluated. Serum samples from 30 healthy volunteers in heparin and 1,4-dithiothreitol-containing tubes stored at −80 °C were analyzed. The MDA-thiobarbituric acid complex was separated from interfering substances using HPLC. For the separation, reverse phase column MAC (4 × 250 mm, Biospher SI 120 PSI C 18 , particle size 7 μm) was used. The mixture of methanol and 8.3 mmol/l phosphate buffer, pH=7.2, (35:65, v/v) was used as mobile phase. The volume of serum samples injected on the column was 50 μl. The analyte was detected at 532 nm. Retention time of MDA-thiobarbituric acid complex was 4.9±0.1 min at the flow rate 0.7 ml/min. Excellent linearity was achieved. The intra- and interassay coefficient of variation was 7.3% and 8.8%, respectively. The recovery was 95.6% and the detection limit was 0.1 μmol/l. The validity of this method was proved by comparison with the spectrophotometric determination of MDA-thiobarbituric acid complex by the method of Yagi at three different wavelengths (485, 532 and 560 nm) with Allen's correction.

June 1, 2005

Precision and Accuracy of a HPLC Method for Measurement of Fecal Porphyrin Concentrations

Floris M. J. Zuijderhoudt, Johannes S. Kamphuis, Willem E. Kluitenberg, Jenneke Dorresteijn-de Bok

Page range: 1036-1039

Abstract

We studied precision and accuracy of a HPLC method for determination of porphyrins in feces. A commercial standard solution appeared to contain less coproporphyrin (15%) than stated by the manufacturer. The between-batch coefficients of variation were often below 15% and were higher than the within-batch coefficients. The precision of porphyrin measurements was not influenced by the type of porphyria. Recoveries of added coproporphyrin and protoporphyrin were 90% and 108%; coefficients of variation were 6% and 19%, respectively.

June 1, 2005

Continuous Age-Dependent Reference Ranges for Thyroid Hormones in Neonates, Infants, Children and Adolescents Established Using the ADVIA(r) Centaur(tm) Analyzer

Ulrich Hübner, Christine Englisch, Heiko Werkmann, Hermann Butz, Thomas Georg, Siegfried Zabransky, Wolfgang Herrmann

Page range: 1040-1047

Abstract

In neonates, infants, children and adolescents serum concentrations of the thyroid hormones show a clear age dependency. Currently, age-dependent thyroid hormone reference ranges for the new ADVIA ® Centaur™ immunoanalyzer are not available. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (T4), free triiodothyronine (FT3) and total triiodothyronine (T3) were determined in the sera of 460 healthy children aged 0 days to 18 years from an inland (n=308) and a seaside city (n=152) using the Bayer ADVIA ® Centaur™ analyzer. Square root functions defining the upper and lower limit of the continuous age-dependent reference range and the median line for each thyroid hormone were estimated applying a parametric regression technique. Continuous age-dependent reference ranges show a better fit to the obtained data than discontinuous reference ranges. The median TSH and FT4 concentrations decrease within the first year of life and are nearly constant until 18 years of age. The median T4 decreases within the entire age interval, whereas the median FT3 is constant. The median T3 increases within the first year of life and decreases afterwards. The calculated continuous reference ranges for T4, T3 and partly FT4 are consistent with published reference ranges. However, the reference ranges obtained for FT3 and partly TSH differed considerably, compared to published reference ranges. No significant residence- or sex-specific effects on age-adjusted hormone concentrations were found except for a slight residence-specific effect on age-adjusted FT4, which was probably due to assay imprecision. Due to the lack of international standardization, the assay-specific evaluation of reference ranges is very important. Continuous age-dependent reference ranges comply better with the biological reality and are more reliable than discontinuous reference ranges.

June 1, 2005

Diagnostic Value of Various Urine Tests in the Jordanian Population with Urinary Tract Infection

Hala I. Al-Daghistani, Muna Abdel-Dayem

Page range: 1048-1051

Abstract

We compared the performance of leukocyte esterase and nitrite reductase dipstick tests with microscopic examination and uroculture in cases with clinically suspected urinary tract infection (UTI). We studied urine specimens from 504 Jordanian patients which were obtained by the mid-stream clean catch method and analyzed for bacteria. All samples were subjected to culture. Results of urine dipstick tests and pyuria (white blood cells (WBC)/high power field) were compared with urine culture for each sample. Significant bacteriuria was found in 117 cases (23.2%) with positivity of 59% and 68.5% for the presence of nitrite reductase and leukocyte esterase, respectively. Echerichia coli was the most common organism isolated. The dipstick leukocyte esterase and nitrite testing had a sensitivity of 68.5% and 59% for detecting bacteriuria in UTI cases and specificity of 73.5% and 78%, respectively. The positive predictive value of the tests was 44% and 60%, and the negative predictive value 88.5% and 86.2%, respectively. Microscopic WBC showed 86.5% specificity but low sensitivity. Urine dipstick results and pyuria significantly correlated with the results of urine culture but demonstrated more false-positive results, which ranged from 13.4–26.6%. The probability of growing a urinary pathogen correlated with urinary WBC counts and allowed prediction of the presence or absence of bacteriuria by counting urinary leukocytes. A combination of pyuria and urine dipstick testing appears to be a very useful marker for the diagnosis of UTI. Urine culture can be omitted if both tests are negative.

June 1, 2005

Performance Evaluation of the Precision™ PCx™ Point-of-Care Blood Glucose Analyzer Using Discriminant Ratio Methodology

Véronique Y. Miendje Deyi, Marianne Philippe, Kathy C. Alexandre, Philippe De Nayer, Michel P. Hermans

Page range: 1052-1055

Abstract

Point-of-care glucose testing needs to be integrated into a laboratory information system to provide continuous care. Selecting a particular glucose monitoring system is based on both analytical performance and on user's preference. We evaluated accuracy, performance and regulatory compliance of the Precision™ PCx™ glucose analyzer (Abbott), with automatic download into a central station, for remote quality control (QC) management and automatic upgrading. We used the discriminant ratio (DR) methodology, which determines the DR of a test ( e.g. the ratio between the underlying SD and the within-subject SD), and compares it to that of another test allegedly measuring the same parameter. Accuracy was evaluated by Clarke's error grid method. Seven hundred and ninety four blood samples were taken from 22 diabetic patients, combined with two capillary blood samples: one for analysis by reference method and the second for PCx™ analysis. Linear regression analysis revealed, over a 2.1 to 26.9 mmol/l glucose concentration range, a correlation coefficient of 0.963, an intercept of 0.7 mmol/l and a slope of 0.851. Mean difference between meter-generated results and the reference method was −7.1±10.8%. Between-run imprecision for PCx™ using Abbott's controls at low and mid-low concentrations was 5.4 and 3.8%, respectively. Clarke's error grid did not show any clinical impact related to difference between methods. DRs were of similar magnitude using both methods. Nursing staff found PCx™ easy for everyday use. Our data show that PCx™ results agree with those obtained with the reference method, as shown by lack of significant difference in DRs, and by excellent correlation.

June 1, 2005

Clinical Evaluation of a New Automated Anti-dsDNA Fluorescent Immunoassay

Monserrat Hernando, Concepción González, Angel Sánchez, Paloma Guevara, José Alejandro Navajo, Wolfgang Papisch, José Manuel González-Buitrago

Page range: 1056-1060

Abstract

The measurement of anti-double-stranded DNA (antidsDNA) antibodies is a useful tool for the diagnosis and the follow-up of systemic lupus erythematosus (SLE). Anti-dsDNA antibodies are involved in the pathogenesis of lupus nephritis and they are, specially the highavidity antibodies, the most specific antibodies associated with SLE nephritis and active SLE. The aim of the present study was to assess the clinical utility of an enzyme-linked immunosorbent assay (ELISA) that utilizes a circular double-stranded plasmid DNA as a nucleic acid source, adapted to an automated fluorescence immunoassay (EliA™ dsDNA, Pharmacia, Freiburg, Germany). Also, we compared this method with other immunoassays used in clinical laboratories. We have measured anti-dsDNA antibodies in the serum of 179 patients with a positive result for antinuclear antibodies (ANA). Seventy six sera were from SLE patients (14men and 62 women), and the other 103 sera (from 20 men and 83 women) constituted the control group. This latter group includes nine Sjögren's syndrome patients, six patients with rheumatoid arthritis and 88 with various other diseases, including connective tissue diseases (n=34), hepatopathies (n=17; 11 primary biliary cirrhosis and 6 autoimmune hepatitis), and 37 patients with nonautoimmune diseases (viral hepatitis, renal disease, diabetes, exanthema and hypertension). Methods used were “EliA™ dsDNA” (Pharmacia, Germany), “Varelisa ® dsDNA” (Pharmacia, Germany), Farr (Amersham, UK) and Chritidia luciliae immunofluorescence test (Vitro-Immun, Germany). We assessed sensitivity, specificity, positive predictive value and negative predictive value in the clinical study, and kappa index and scatter plots in the comparative study. The results show a low concordance between methods (κ<0.6). The evaluated EliA method shows a very good specificity for SLE (93.2%) and a good sensitivity for active SLE (70.8%).

June 1, 2005

Upper Reference Limits for Urinary Catecholamines, Metanephrines and 3-Methoxy-4-Hydroxymandelic Acid in Hypertensive Patients

Milan Skitek

Page range: 1061-1062

June 1, 2005

Growth Hormone Immunoassays: Proposal to Reduce Interlaboratory Variability

Ellen Anckaert, Johan Schiettecatte, Johan Smitz, Jesse Vanbesien, Jean De Schepper

Page range: 1063-1065

June 1, 2005

Poetry, Images and Visions: William Blake

Marek H. Dominiczak

Page range: 1066-1070

Abstract

This article focuses on the work of William Blake (1757–1827), British artist, poet and engraver. Blake is discussed as a thinker opposed to the ‘tyranny of reason’ interpreted as rational philosophies promoted with a religious zeal. The visionary, mystical character of some of Blake's works is contrasted with his eclectic reading and sharp social criticism. Blake's work is related to the early discourse on science. The article is supported by the images of his two works, the ‘Ancient of Days’ and the ‘Newton’.

July 27, 2005

Meetings and Awards

Page range: 1071-1073

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 8. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

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Topics

clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
new reagents, instrumentation and technologies
new methodologies
reference materials and methods
reference values and decision limits
quality and safety in laboratory medicine
translational laboratory medicine
clinical metrology

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers on all aspects of clinical chemistry and laboratory medicine, Guidelines and Recommendations, Point/Counterpoint Articles, Letters to the Editor, Editorials

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