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Maternal smoking and fetal erythropoietin levels.

OBJECTIVE: To determine the influence of maternal smoking on fetal erythropoietin concentrations in health term pregnancies and test the correlation between cotinine, a biomarker of maternal smoking, and erythropoietin levels in fetuses. METHODS: We invited women with healthy term pregnancies to participate in the study, excluding those with conditions previously known to be associated with elevated fetal erythropoietin levels. We recorded demographic data, smoking status, and labor outcome prospectively for each patient. Umbilical venous samples were collected, and serum was stored at -70C to be analyzed later for erythropoietin and cotinine. Umbilical arterial samples were tested for pH and base excess determination. We compared fetal erythropoietin and cotinine between smokers and nonsmokers and examined correlations between erythropoietin and cotinine. Kruskal-Wallis test, t test, median test, and Spearman rank correlation test were used when appropriate. Statistical significance was P <.05. RESULTS: We recruited 35 nonsmokers and 26 smokers and analyzed their samples. The two groups were comparable in demographics and birth outcomes, except for birth weights, which were lower in smokers. Fetal erythropoietin concentrations increased significantly with increasing maternal cigarette consumption, ranging from none to more than 15 cigarettes per day (P =.03). There was positive correlation between fetal erythropoietin and cotinine concentrations (r =.41; P =.04), suggesting a dose-response relationship. CONCLUSION: Fetuses of smokers had increased erythropoietin concentrations that correlate positively with fetal cotinine levels; which suggests an increased risk of subacute hypoxia related to degree of maternal cigarette consumption.

Adult↗

Many accurate small-discriminatory feature subsets exist in microarray transcript data: biomarker discovery.

BACKGROUND: Molecular profiling generates abundance measurements for thousands of gene transcripts in biological samples such as normal and tumor tissues (data points). Given such two-class high-dimensional data, many methods have been proposed for classifying data points into one of the two classes. However, finding very small sets of features able to correctly classify the data is problematic as the fundamental mathematical proposition is hard. Existing methods can find "small" feature sets, but give no hint how close this is to the true minimum size. Without fundamental mathematical advances, finding true minimum-size sets will remain elusive, and more importantly for the microarray community there will be no methods for finding them. RESULTS: We use the brute force approach of exhaustive search through all genes, gene pairs (and for some data sets gene triples). Each unique gene combination is analyzed with a few-parameter linear-hyperplane classification method looking for those combinations that form training error-free classifiers. All 10 published data sets studied are found to contain predictive small feature sets. Four contain thousands of gene pairs and 6 have single genes that perfectly discriminate. CONCLUSION: This technique discovered small sets of genes (3 or less) in published data that form accurate classifiers, yet were not reported in the prior publications. This could be a common characteristic of microarray data, thus making looking for them worth the computational cost. Such small gene sets could indicate biomarkers and portend simple medical diagnostic tests. We recommend checking for small gene sets routinely. We find 4 gene pairs and many gene triples in the large hepatocellular carcinoma (HCC, Liver cancer) data set of Chen et al. The key component of these is the "placental gene of unknown function", PLAC8. Our HMM modeling indicates PLAC8 might have a domain like part of lP59's crystal structure (a Non-Covalent Endonuclease lii-Dna Complex). The previously identified HCC biomarker gene, glypican 3 (GPC3), is part of an accurate gene triple involving MT1E and ARHE. We also find small gene sets that distinguish leukemia subtypes in the large pediatric acute lymphoblastic leukemia cancer set of Yeoh et al.

Biomarkers↗

Serum cardiac troponin T and creatine kinase-MB elevations in murine autoimmune myocarditis.

BACKGROUND: We used a murine model of autoimmune myocarditis to investigate systematically whether serum markers of myocardial cell injury, that is, cardiac troponin T (TnT) and the MB isoenzyme of creatine kinase (CK-MB) are useful for the diagnosis of inflammatory heart disease. METHODS AND RESULTS: Fifty-two A.SW mice were immunized with cardiac myosin to induce myocarditis. The disease was evident on day 12 after the initial immunization in 14 of 22 immunized mice, on day 16 in 7 of 10 mice, on day 19 in 6 of 10 mice, and on day 23 in 5 of 10. The severity of myocarditis increased between days 12 and 16 and remained constant thereafter. TnT was elevated in a considerable number of mice with myocarditis, resulting in a diagnostic sensitivity (number of marker elevations per number of mice with myocarditis) of 0.43 on day 12, 0.71 on day 16, and 0.50 on day 19. CK-MB elevations were not seen on day 12 but resulted in a diagnostic sensitivity of 0.71 on day 16 and of 0.33 on day 19. No elevations of CK-MB or TnT were observed on day 23. All elevations were specific for the disease, as none of the mice lacking myocarditis showed increased markers. CONCLUSIONS: In murine autoimmune myocarditis, TnT is a more sensitive marker for the disease than CK-MB. Elevations clearly indicate myocarditis, but negative test results do not exclude the presence of the disease. These data suggest that the determination of CK-MB and, in particular, of TnT, can be useful for the diagnostic evaluation of patients with suspected myocarditis.

Animals↗

A urinary marker of alcohol intake.

Previously, one of us (B. K. T.) developed an assay that measures levels of free ethanol and ethanol conjugates in urine and showed that the mean levels of these ethanol markers in confirmed alcoholics were at least 20-fold higher than those levels in control subjects. In this study, we assessed the relationship of these biomarkers with self-reported levels of alcohol intake in a multiethnic sample of Los Angeles County residents who were male and over the age of 35 years (n = 128; 40 non-Hispanic whites, 46 blacks, 17 Chinese, and 25 Japanese). Regardless of race, the mean levels of free, bound, and total (free plus bound) ethanol were lowest in nondrinkers, intermediate in weekly drinkers, and highest in daily drinkers (P = 0.0001 in all three statistical tests of differences in the three biomarkers). Stepwise discriminant analysis showed that of the three potential biomarkers, total ethanol best discriminates between the three classes of drinkers (non, weekly, and daily), and that additional inclusion of either free or bound ethanol in the discriminant function had negligible effect. Overall, mean level of total ethanol was 2.2 times higher in weekly than in nondrinkers; daily drinkers, in turn, showed a 4.2-fold increase in mean total ethanol relative to weekly drinkers. However, there was no correlation between any of the three biomarkers and self-reported level (in grams of ethanol) of average consumption in either weekly or daily drinkers whose mean intake was about 13 and 42 g of ethanol/day, respectively. As the level of urinary free ethanol and ethanol conjugates showed extraordinary differences among racial groups for a given level of self-reported ethanol intake, the data suggest possible interracial differences in the in vivo elimination rate of ethanol; this latter finding needs to be confirmed in larger studies.

Adult↗

Reliable screening for acute pancreatitis with rapid urine trypsinogen-2 test strip.

BACKGROUND: This study was designed to evaluate the validity of a new rapid urinary trypsinogen-2 test strip (Actim Pancreatitis) for detection of acute pancreatitis in patients with acute abdominal pain. METHODS: A total of 525 consecutive patients presenting with abdominal pain at two emergency units was included prospectively and tested with the Actim Pancreatitis test strip. Urine trypsinogen-2 concentrations were also determined by a quantitative method. The diagnosis and assessment of severity of acute pancreatitis was based on raised serum and urinary amylase levels, clinical features and findings on dynamic contrast-enhanced computed tomography. RESULTS: In 45 patients the diagnosis of acute pancreatitis could be established. The Actim Pancreatitis test strip result was positive in 43 of them resulting in a sensitivity of 96 per cent. Thirty-seven false-positive Actim Pancreatitis test strips were obtained in patients with non-pancreatic abdominal pain resulting in a specificity of 92 per cent. Nine patients with severe acute pancreatitis were all detected by the dipstick. CONCLUSION: A negative Actim Pancreatitis strip result excludes acute pancreatitis with high probability. Positive results indicate the need for further evaluation, i.e. other enzyme measurements and/or radiological examinations. The test is easy and rapid to perform, unequivocal in its interpretation and can be used in healthcare units lacking laboratory facilities.

Abdominal Pain↗

Analysis of granzyme B activity as a surrogate marker of Leishmania-specific cell-mediated cytotoxicity in zoonotic cutaneous leishmaniasis.

The purpose of this study was to analyze Leishmania-specific cell-mediated cytotoxicity in individuals with active or healed zoonotic cutaneous leishmaniasis (ZCL). The (51)Cr-release assay revealed a significant cytotoxicity against L. major-infected autologous macrophages in individuals with active or healed ZCL. As a surrogate marker of cytotoxic response, a test based on the measure of granzyme B activity in parasite-stimulated peripheral blood mononuclear cells was optimized and evaluated in 88 individuals. Increased granzyme B activity was found in 62.5% of patients with active ZCL and in only 30% of individuals with healed ZCL. In both groups, granzyme B activity was significantly higher than in healthy, leishmanin skin test-negative control subjects (P<.05). These data provide additional evidence that Leishmania-specific cell-mediated cytotoxicity is part of the acquired immune response developed against the parasite. Its role in resistance to reinfection should be evaluated.

Adolescent↗

Periodontal disease diagnosis: current status and future developments.

OBJECTIVES: This manuscript attempts to critically review traditional and currently employed methods of periodontal diagnosis, in the light of current knowledge about individual patients and sites at risk of progressive periodontal attachment loss. DATA SOURCES: Articles published over the last decade from international research journals, have demonstrated that existing methods of periodontal disease diagnosis are seriously deficient with respect to accuracy, their ability to predict ongoing or future disease activity and their ability to determine the current activity status of historically diseased sites. STUDY SELECTION: Longitudinal studies have questioned the rationale behind traditional treatment regimes and underlined the importance of site-directed therapy to avoid potentially damaging instrumentation of quiescent or healthy sites. The recent explosion in local, less invasive chemotherapies for periodontal disease management has aimed at addressing the site-specific nature of this group of diseases, but the true benefits of such novel therapies cannot be realised until more accurate and specific diagnostic techniques become available. CONCLUSIONS: The manuscript concludes that the range of clinical information collected by experienced periodontists using currently available technology is probably sufficient to manage mild-to-moderate chronic adult periodontitis. However, those patients at risk from more aggressive attachment loss, and those individuals that appear refractory to traditional therapies, require the development of more accurate diagnostic tests to compliment the revolution in site-specific therapies. A diagnostic model is presented, which attempts to draw together current and future diagnostic methods for managing the majority of periodontal disease types, and it is suggested that current diagnoses should include some assessment of "risk'.

Adult↗

[Therapeutic goals and outcome measurements in COPD patients].

Due to the complex pathogenesis of chronic obstructive pulmonary disease (COPD) with systemic effects and different subjective perceptions, responses to therapy are difficult to assess. Though lung function tests correlate poorly with important features of the disease such as survival and quality of life, spirometric measures, especially forced expiratory volume (FEV(1)) and inspiratory capacity, the 6-min walk test, exacerbation indices, dyspnea scales and health status measurements remain important outcomes in clinical studies as well as in clinical practice. Markers of airway inflammation are receiving increased attention. The BODE index, combining functional and systemic outcomes, is a better predictor of mortality than FEV(1) and, therefore, particularly valuable.

Adult↗

Discriminating different classes of toxicants by transcript profiling.

Male rats were treated with various model compounds or the appropriate vehicle controls. Most substances were either well-known hepatotoxicants or showed hepatotoxicity during preclinical testing. The aim of the present study was to determine if biological samples from rats treated with various compounds can be classified based on gene expression profiles. In addition to gene expression analysis using microarrays, a complete serum chemistry profile and liver and kidney histopathology were performed. We analyzed hepatic gene expression profiles using a supervised learning method (support vector machines; SVMs) to generate classification rules and combined this with recursive feature elimination to improve classification performance and to identify a compact subset of probe sets with potential use as biomarkers. Two different SVM algorithms were tested, and the models obtained were validated with a compound-based external cross-validation approach. Our predictive models were able to discriminate between hepatotoxic and nonhepatotoxic compounds. Furthermore, they predicted the correct class of hepatotoxicant in most cases. We provide an example showing that a predictive model built on transcript profiles from one rat strain can successfully classify profiles from another rat strain. In addition, we demonstrate that the predictive models identify nonresponders and are able to discriminate between gene changes related to pharmacology and toxicity. This work confirms the hypothesis that compound classification based on gene expression data is feasible.

Algorithms↗

Leucocyte elastase as a marker in the diagnosis of acute appendicitis.

OBJECTIVE: To investigate the value of measuring the activity of the leucocyte elastase complex in plasma in the diagnosis of acute appendicitis, either as a single or four-hourly test. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: 165 consecutive patients admitted with suspected acute appendicitis. MAIN OUTCOME MEASURES: Correlation of concentrations of leucocyte elastase complex (elastase) and total white blood cell count (WBC) with C-reactive protein concentration and histological appearance of the appendix. RESULTS: Of 165 patients, 101 patients had their appendixes removed, and of these 86 had histologically confirmed appendicitis. An elastase value of less than 54 micrograms/l was considered to be the reference range. Elastase activity measured on admission gave a sensitivity of 61% and a specificity of 43% for acute appendicitis compared with the WBC which had a sensitivity of 81% and a specificity of 36%. The above blood tests were taken on two or more occasions four hourly after admission in 29 patients. Appendicitis was found in 25 of the 29 cases (87%), in which repeated tests showed a significant reduction in WBC together with a definite but not significant reduction in the elastase activity during the preoperative period. Repeated tests were of no value. CONCLUSIONS: Measurement of the leucocyte elastase complex in plasma does not increase the accuracy of the diagnosis of acute appendicitis. There was no significant correlation between the leucocyte elastase activity and the total white cell count.

Acute Disease↗

Hemostasis during normal pregnancy and puerperium.

During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications in connection with delivery. The most important initial factor for acute hemostasis at delivery is, however, uterine muscle contractions, which interrupt blood flow. Global tests such as Sonoclot signature, the Thromboelastogram, and a new method analyzing overall plasma hemostasis, all show changes representative of hypercoagulability during pregnancy. Increased endogenous thrombin generation, acquired activated protein C resistance, slightly decreased activated partial thromboplastin time (aPTT) and increased prothrombin complex level (PT) measured as international normalized ratio (INR) of less than 0.9 have been reported as well. In normal pregnancy, the platelet count is within normal range except during the third trimester when benign gestational thrombocytopenia, 80 to 150 x 10 9/L, can be observed. Platelet turnover is usually normal. Activation of platelets and release of beta-thromboglobulin and platelet factor 4 are reported. The bleeding time is unchanged during normal pregnancy. Most blood coagulation factors and fibrinogen increase during pregnancy. Factor (F) XI is the only blood coagulation factor that decreases. Blood coagulation inhibitors are mainly unchanged but the level of free protein S decreases markedly and the level of tissue factor pathway inhibitor increases. Thrombomodulin levels increase during pregnancy. Fibrinolytic capacity is diminished during pregnancy, mainly because of markedly increased levels of plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and plasminogen activator inhibitor-2 (PAI-2) from the placenta. Thrombin-activated fibrinolysis inhibitor is reported to be unaffected. The total hemostatic balance has been studied by analyses of prothrombin fragment 1+2, thrombin-antithrombin complex, fibrinopeptide A, soluble fibrin, D-dimer, and plasmin-antiplasmin complex. There is activation of blood coagulation and a simultaneous increase in fibrinolysis without signs of organ dysfunction during normal pregnancy. These changes increase as pregnancy progresses. During delivery, there is consumption of platelets and blood coagulation factors, including fibrinogen. Fibrinolysis improves and increases fast following childbirth and expulsion of the placenta, resulting in increased D-dimer levels. These changes are self-limiting at normal delivery. The hemostatic changes, noted during pregnancy, normalize after delivery within 4 to 6 weeks. Platelet count and free protein S, however, can be abnormal longer. Hemostasis should not be tested earlier than 3 months following delivery and after terminating lactation to rule out influences of pregnancy. PAI-1 and PAI-2 levels decrease fast postpartum, but PAI 2 has been detected up to 8 weeks postpartum. alpha 2 -antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be increased 6 weeks postpartum.

Biomarkers↗

Technical aspects of the development and validation of tests for variant Creutzfeldt-Jakob disease in blood transfusion.

The development of tests for variant Creutzfeldt-Jakob disease in the context of blood transfusion is technically complicated by a number of factors, including the long asymptomatic period and uncertainty as to whether infectivity is present in human blood at all. The specific needs of a donor test impose constraints. It is argued that the only possible analyte will be blood, and that while the initial work will involve animal studies, these will provide only an approximate guide. A rapid infectivity assay is key to confirming positives in human samples, and dilutions of infected human brain will probably provide adequate routine control samples to ensure the correct performance of the test.

Animals↗

Rationale for testing the cardiovascular risk for patients with COX-2 inhibitors on the basis of biomarker NT-proBNP.

Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2 inhibitors constitutes a potential risk for the increased occurrence of thrombotic cardiovascular incidents and of the first-time occurrence or a deterioration in pre-existing heart failure. Elderly patients, particularly those with a history of ischemic heart disease, hypertension or heart failure, are at risk. One key indication for selective COX-2 inhibitors is the chronic treatment of patients suffering from rheumatoid arthritis or osteoarthritis. However, these patients have an excess cardiovascular mortality, which relates particularly to cardiovascular incidents or heart failure. The use of nonselective antiphlogistic drugs and COX-2 inhibitors is associated with a higher potential risk in these patient groups. In essence, more than 80 million patients worldwide were treated with rofecoxib up to its voluntary withdrawal. The high number of patients who are still being treated with COX-2 inhibitors or for whom the use of COX-2 inhibitors is planned justifies the use of a biochemical marker which, as a screening instrument, is initially designed to recognize the patients who are "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP levels below the cut-off, high-risk patients require further work-up. Recognition of these risk factors is easily accomplished considering the case history and the results of an established cardiovascular risk score (e.g. PROCAM score). These risk patients should then also be referred for intensive diagnostic work-up. On the other hand, symptomatic patients or those with high NT-proBNP levels should primarily be referred for more extensive cardiovascular diagnosis before a decision is taken concerning the use of COX-2 inhibitors. As an integral part of this extensive work-up the determination of NT-proBNP can help to improve the accuracy of diagnosis and prognostic assessment. With the exception of patients showing symptoms of an unstable coronary heart disease, imminent cerebral ischemia, uncontrolled arterial hypertension or decompensated heart failure, the use of a COX-2 inhibitor is possible provided special caution is exercised. Termination of treatment is advisable if there is a clinical deterioration of specific symptoms or signs in those patients (product information). Follow-up with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac decompensation at an earlier stage in order to take suitable countermeasures.

Aged↗

Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid-hyaluronidase and BTA-Stat tests.

BACKGROUND: One of the goals of a noninvasive test for bladder carcinoma screening would be to reduce surveillance cystoscopies among patients with a history of bladder carcinoma. In addition, an accurate bladder carcinoma marker could be used to screen a high-risk population. The authors examined the efficacy of the hyaluronic acid-hyaluronidase (HA-HAase) and BTA-Stat tests to detect and predict bladder carcinoma recurrence and tested their specificity for bladder carcinoma screening. METHODS: Over a four year period, the authors prospectively collected 225 urine specimens from 70 bladder carcinoma patients and analyzed them by the HA-HAase test. Tumors were identified during 178 visits, and in 47 specimens there was no evidence of disease (NED). Twenty six of these 70 patients were randomly selected to have the BTA-Stat test (111 surveillance visits). In a separate study, 401 former Department of Energy (DOE) workers, who are likely to be at a higher risk for bladder carcinoma, were screened by the HA-HAase and BTA-Stat urine tests. RESULTS: The HA-HAase test had an approximately 91.0% sensitivity, 70% specificity, 87% accuracy, 92% positive predictive value (PPV), and 67% negative predictive value (NPV) in the 70 bladder carcinoma patients. There were 14 false-positives; however, 6 of these had recurred in approximately 5 months. Only 4 out of 33 NED cases recurred in that time period (chi-square = 5.43; degrees of freedom [DF] = 1; P = 0.0198). Thus, a false-positive HA-HAase test carried a significant risk of recurrence within five months (relative risk [RR] = 3.5; odds ratio [OR] = 5.44). In a direct comparison, the HA-HAase and BTA-Stat had 94% and 61% sensitivity, 63% and 74% specificity, 87% and 64% accuracy, 89% and 88% PPV, and 77% and 38% NPV, respectively. While 6 of the 10 false-positive on the HA-HAase test recurred in 5 months (chi-square = 9.6; DF = 1; P = 0.004), only 1 of the 7 false-positives on the BTA-Stat test recurred in that time period (chi-square = 0.096; DF = 1; P = 0.756). The RR and OR for the HA-HAase test were 10.2 and 24, and for the BTA-Stat, 1.4 and 1.5, respectively. In the DOE worker screening study, the HA-HAase and BTA-Stat had 14% (56 out of 401) and 16.7% (67 out of 401) positive rates, respectively. Sixty three percent of the positives on the BTA-Stat test, but only 25% of the positives on the HA-HAase test, had benign urologic conditions. None of the biomarker positive cases with clinical follow-up (n = 29) had evidence of bladder carcinoma. CONCLUSIONS: The HA-HAase test is efficient and superior to the BTA-Stat for detecting and predicting bladder carcinoma recurrence. Noninvasive tests with low false positive rates could be used for bladder carcinoma screening in high-risk populations (e.g., those with occupational exposure to carcinogens or smokers).

Biomarkers, Tumor↗

Complex chromosomal rearrangements induced in vivo by heavy ions.

It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects.

Aged↗

Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients.

BACKGROUND: In clinical practice, the assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Therefore, this study was designed to determine whether the serum cystatin C (Cys C) and activities of some tubular enzymes could be used as screening markers for renal dysfunction in diabetic patients. METHODS: Serum Cys C levels and urinary activities of N-acetyl-b-D-glucosaminidase (NAG), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and whole blood glycolyse hemoglobin (HbA1C) were measured in 56 diabetic patients and 20 healthy subjects (controls). The results were compared with serum creatinine (Cr) and creatinine clearance (CCr), which were measured and estimated with the Cockcroft-Gault formula (CCG) and 24-hr urine microalbuminuria (MAU). We examined the influence of albuminuria, HbA1C and CCr levels of patients on the levels of the analyzed parameters. Sensitivity and specificity for the diagnosis of renal impairment were calculated by a receiver operating characteristics (ROC) curve for serum Cys C, Cr and urinary enzymes. RESULTS: In normoalbuminurics, only serum Cys C levels and urinary NAG activities were found elevated as compared to controls. In addition to the elevation of serum Cys C levels and urinary activities of NAG, urinary ALP and LDH activities were also found elevated in microalbuminurics. Serum Cys C levels and urinary NAG, ALP, LDH activities started to increase above the normal range when CCr declined and while serum Cr was in the normal range in patients with 50<CCr<80 (grade 2 group). Moreover, these parameters in patients with good metabolic control were significantly lower than in patients with poor metabolic control. There was a significant positive correlation between serum Cys C, urinary NAG, LDH, ALP activities and serum Cr levels. However, there was an inverse correlation between serum Cys C, urinary NAG, LDH, ALP and CCr and CCG in diabetic patients. The ROC plot indicated that serum Cys C and urinary NAG and ALP had higher sensitivity than serum Cr and met the criteria for detecting glomerular and tubular dysfunction as screening tests for early diagnosis of diabetic nephropathy. CONCLUSION: This study demonstrated that measuring serum Cys C levels and urinary NAG, ALP and LDH activities could be useful as screening markers to follow-up glomerular and tubular dysfunction in diabetic patients.

Acetylglucosaminidase↗

IFCC Committee on Standardization of Markers of Cardiac Damage: premises and project presentation. International Federation of Clinical Chemistry and Laboratory Medicine.

The field of biochemical markers of cardiac damage is in a dynamic state, with new applications continually appearing and new assays and markers being developed. These significant and sudden advancements in the development of new biochemical assays have led however to several analytical and interpretative problems. In this situation, it is essential that a uniform and rigorous outlook be maintained to ensure optimal test utilization. For these reasons, the IFCC Scientific Division recently agreed to establish a Committee on "Standardization of Markers of Cardiac Damage" (C-SMCD), inviting members from the established American and European groups to become members of this Committee. In this presentation, the premises, the issues, and the proposed plan of action of C-SMCD are presented and discussed.

Biomarkers↗