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M Panteghini

Publications and source records attributed to M Panteghini.

At least 19 recordsLinked to original sources

The exciting story of cardiac biomarkers: from retrospective detection to gold diagnostic standard for acute myocardial infarction and more.

This paper reviews the history of the contribution of the laboratory medicine to clinical cardiology and discusses the most important steps in this field. Until 20 years ago, the clinical laboratory only placed at the cardiologist's disposal a few assays for the retrospective detection of cardiac tissue necrosis, such as enzymatic methods for creatine kinase and lactate dehydrogenase activities. However, in the latter part of the 20th century, highly sensitive and specific assays, such as cardiac troponins, as well as assays for markers of myocardial function, such as cardiac natriuretic peptides, rapidly changed the scenario of clinical management of patients with cardiac diseases, assigning to the laboratory a pivotal role in the overall diagnostic flow. This is witnessed by the recent incorporation of these markers into international guidelines and in the redefinition of myocardial infarction. For the foreseeable future, new serum markers of myocardial ischemic, i.e. reversible, injury or related to coronary plaque instability and disruption are expected.

Acute Disease↗

Standardization in laboratory medicine: new challenges.

The primary goal of Laboratory Medicine is to provide information that is useful to assist medical decision-making and permits optimal health care. This type of information should be independently obtained of the measurement test kits and instruments, and also of the laboratory where the procedure is carried out. It is therefore important to achieve a level of comparability of laboratory results among the many measurement procedures available so that results are harmonized and interchangeable over space and time. The standardization of measurements is therefore of high priority. In recent years, numerous efforts have been made at the international level under the auspices of the IFCC and other organizations to standardize measurement results for many important analytes, e.g. enzymes, cardiac proteins, etc. The aim of this review is to discuss some concepts related to the achievement of standardization by the implementation of a metrologically correct measurement system, providing some examples on how these concepts can be applied in Laboratory Medicine.

Chemistry, Clinical↗

Recent approaches in standardization of cardiac markers.

The development of commercial assays for the determination of new cardiac proteins has been one of the most important innovations in the field of cardiovascular diagnostics in the last decade. This significant and sudden advancement has however led to some analytical and interpretative problems. There are problems in test standardization, imprecision, interference and preanalytical variability. We also need to standardize utilization of biomarkers in diagnosis and management of acute cardiac syndromes and clearly define decision thresholds. Powerful tests, such as cardiac markers, on which critical decisions will rest, need highly reliable methods. The feeling is that some assays are inadequately appraised prior to their introduction in clinical use. More studies are needed to implement new devices in the laboratory routine, and only well documented assays should be used in hospital-based laboratories. The technology to address many analytic problems is at hand, but commitment on the part of manufacturers and their customers in the laboratory community is essential.

Animals↗

Comparative study of cardiac troponin I and T measurements in a routine extra-cardiological clinical setting.

This study compared troponin I (cTnI) to troponin T (cTnT) in a population admitted to General Medicine Divisions in whom acute myocardial infarction (AMI) was suspected; 98 consecutive patients were included. Diagnoses were made without knowledge of troponin results: 51 patients had AMI, and 47 (including 8 with unstable angina) had no AMI. Patients were considered to be troponin positive if the marker concentration was >99th percentile value of the reference population. Both troponins were associated with an almost absolute sensitivity for AMI (100% for cTnI and 98.0% for cTnT), while the specificity was marginally higher for cTnI (78.7% vs. 68.1%). Increased cTnI and/or cTnT were observed in 15 patients out of 39 without acute coronary syndromes. Simultaneous positivity was seen in 8 patients with severe disorders and complications. Discordances were more frequent in favor of increased cTnT (n = 5) than the opposite (n = 2), even if this difference did not achieve statistical significance. cTnI and cTnT detected AMI with comparable efficiency. Cases without coronary syndrome positively concordant for troponins confirmed the ability of these biomarkers to detect myocardial injury undetectable by conventional diagnostic approaches.

Adult↗

Controlled fetal blood-letting of the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome: preliminary results.

OBJECTIVE: To investigate the feasibility of withdrawal of blood from the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome. METHODS: Seven consecutive monozygotic monochorionic twin pregnancies affected by severe twin-twin transfusion syndrome were treated. Fetal blood was withdrawn from the recipient twin using cordocentesis. The volume of blood to be removed was determined using the formula for intrauterine blood transfusion of anemic fetuses. Fetal outcome was evaluated in relation to changes in the amniotic fluid and in growth curves (comparing the differences between the centiles of the estimated fetal weight before the procedure and the centiles of weight at birth), fetal mortality, gestational age at delivery, neonatal weight and neurological damage. RESULTS: Overall, seven of the 14 (50%) fetuses survived; at least one fetus survived in five (71%) pregnancies, both fetuses survived in two (29%) pregnancies, while in two (29%) pregnancies there were no survivors. No maternal complications were observed. At follow-up, one (14%) baby had minor neurological damage. CONCLUSIONS: Withdrawal of blood from the recipient twin in the treatment of severe twin-twin transfusion syndrome was associated with survival similar to that of the alternative techniques of serial amniodrainage and fetoscopic laser surgery, with some possible advantages such as reduced neurological damage compared with serial amniodrainage. It is also less invasive compared with fetoscopic laser surgery.

Cordocentesis↗

Recent approaches to the standardization of cardiac markers.

The development of commercial assays for the determination of cardiac proteins has been one of the most important innovations in the field of cardiovascular diagnostics in the last decade. Some assays are, however, inadequately appraised prior to their introduction to clinical use. This paper focuses on some important preanalytical, analytical and interpretative problems, and summarizes the status of the ongoing local and international standardization efforts. The most urgent issue at the moment is the development of international reference materials, which can be used for the calibration of different assays, thus decreasing between-assay biases. In order to achieve comparability of test results, another important item is the standardization of the epitopes of the antibodies used for the assay development. Efforts to improve the precision of cardiac marker assays are also warranted. Finally, the effect of storage time and temperature on apparent marker concentration and the possible influence of different anticoagulants on measured marker values should clearly be evaluated.

Biomarkers↗

Measurement of pancreatic lipase activity in serum by a kinetic colorimetric assay using a new chromogenic substrate.

We evaluate a new assay reagent for lipase determination, based on the use of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) as substrate. DGGR is cleaved by lipase, resulting in an unstable dicarbonic acid ester which is spontaneously hydrolysed to yield glutaric acid and methylresorufin, a bluish-purple chromophore with peak absorption at 580 nm. The rate of methylresorufin formation is directly proportional to the lipase activity in the sample. Bile salts, colipase and calcium chloride are included to provide optimal reactivity and specificity. Analysis of total imprecision gave a coefficient of variation of between 5.7% and 9.6%. Anticoagulants, common interfering substances and carboxylesterase had no effect on the assay, but interference by increased concentrations of serum triglycerides was noted. Good correlations were obtained with turbidimetry and a coupled enzymatic method. The estimated reference interval was 6-38 U/L. The unique characteristics of the chromogenic substrate qualify the present method as an innovative approach to serum lipase analysis.

Anticoagulants↗

Establishing a reference system in clinical enzymology.

The goal of standardization for measurements of catalytic concentrations of enzymes is to achieve comparable results in human samples, independent of the reagent kits, instruments and laboratory where the procedure is carried out. To pursue this objective, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has launched a project to establish a reference system in clinical enzymology. This system is based on three hinges: a) extensively evaluated and carefully described reference procedures, b) certified reference materials and c) a network of reference laboratories operating in a highly controlled manner. The original IFCC-recommended procedures for alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma-glutamyltransferase, lactate dehydrogenase and alpha-amylase have been slightly modified to optimize them at 37 degrees C, with the definition of detailed operating procedures. A group of laboratories perform these procedures manually, with self-made reagents on carefully calibrated instruments. Partially purified and stabilized materials, prepared in the past by the Community Bureau of Reference, have been re-certified by these laboratories for alanine aminotransferase, creatine kinase, gamma-glutamyltransferase and lactate dehydrogenase activities. Using these materials and the manufacturer's standing procedures, industry can assign traceable values to commercial calibrators. Thus, clinical laboratories, which will use routine procedures with these validated calibrators to measure human specimens, can finally obtain values which are traceable to reference procedures.

Calibration↗

Certification of the mass concentration of creatine kinase isoenzyme 2 (CK-MB) in the reference material BCR 608.

We describe the certification of a mass concentration value in the already prepared creatine kinase-2 reference material (BCR 608). Creatine kinase-2 was purified from human heart. The purified enzyme was diluted in order to measure its protein concentration by the Doetsch method. A protein concentration value of 124.30+/-13.17 mg/l was assigned to the stock solution of purified creatine kinase-2. This stock solution was diluted in 25 mmol/l piperazine-N,N'-bis[2-ethanesulfonic acid] (PIPES) pH 7.2, containing 2 mmol/l ADP, 5 mmol/l 2-mercaptoethanol, 154 mmol/l sodium chloride and 50 g/l human albumin to obtain a stable liquid standard of known creatine kinase-2 mass concentration (80.36 microg/l). This standard was then used to recalculate the creatine kinase-2 mass concentration measured in the BCR 608 material by immunoassay. The mass concentration of creatine kinase-2 in samples of reconstituted BCR 608 was certified to be 93.30+/-9.65 microg/l.

Calibration↗

Standardization of cardiac troponin I assays: round Robin of ten candidate reference materials.

BACKGROUND: Cardiac troponin I (cTnI) results vary 100-fold among assays. As a step toward standardization, we examined the performance of 10 candidate reference materials (cRMs) in dilution studies with 13 cTnI measurement systems. METHODS: Solutions of 10 cTnI cRMs, each characterized by NIST, were shipped to the manufacturers of 13 cTnI measurement systems. Manufacturers used their respective diluents to prepare each cRM in cTnI concentrations of 1, 10, 25, and 50 microg/L. For the purpose of ranking the cRMs, the deviation of each cTnI measurement from the expected response was assessed after normalization with the 10 microg/L cTnI solution. Normalized deviations were examined in five formats. Parameters from linear regression analysis of the measured cTnI vs expected values were also used to rank performance of the cRMs. RESULTS: The three cRMs demonstrating the best overall rankings were complexes of troponins C, I, and T. The matrices for these three cRMs values differed; one was reconstituted directly from the lyophilized form submitted by the supplier; one was submitted in liquid form, lyophilized at NIST, and subsequently reconstituted; and the third was evaluated in the liquid form received from the supplier. The cRM demonstrating the fourth best performance was a binary complex of troponins C and I supplied in lyophilized form and reconstituted before distribution. CONCLUSIONS: The cRMs demonstrating the best performance characteristics in 13 cTnI analytical systems will be included in subsequent activities of the cTnI Standardization Committee of the AACC.

Algorithms↗

Present issues in the determination of troponins and other markers of cardiac damage.

OBJECTIVE: To review some of the recently proposed improvements and the corresponding apparent issues in the field of biochemical markers of cardiac damage. CONCLUSIONS: The continuous development of new analytical tools for the biochemical evaluation of patients with suspected myocardial injury brings without doubt new challenges of careful technological evaluation, implementation, and standardization but it may also provide a unique opportunity to markedly enhance our diagnostic performance in the clinical setting of acute coronary syndrome.

Biomarkers↗

Evaluation of a fully automated assay to measure C-telopeptide of type I collagen in serum.

The measurement of the degradation product of the C-telopeptide of type I collagen in serum (s-betaCTX) has been evaluated in the form of an automated chemiluminometric assay. The between-day coefficients of variation ranged between 2.6 and 6.0% over the concentration range 0.12 to 3.25 microg/l. The s-betaCTX value correlated well with alternative serum C-telopeptide (r = 0.983) and urine deoxypyridinoline (r = 0.729) measurements. A significant inverse correlation was found between the s-betaCTX measurement and creatinine clearance in patients with renal disease.

Adult↗