Fisiopatologia del tessuto osseo nelle neoplasie di interesse ematologico: il modello del mieloma multiplo

M. De Matteo, L. Lombardi, C. Quatraro, F. Silvestris, P. Cafforio
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Bari

Biochimica Clinica: 2007; 31(3): 175-179 [Article in italian]

ABSTRACT. Bone pathophysiology in hematological tumors: the multiple myeloma model. Bone is a dynamic tissue and undergoes continuous remodeling promoted by both osteoblasts and osteoclasts. Bone homeostasis is physiologically balanced between matrix synthesis by osteoblasts and resorption by osteoclasts, thus ensuring the function maintenance. Pathological involvement of bone during inflammatory diseases or tumors may induce osteoclast hyperactivation and concurrent derangement of osteoblast function associated to variation of serum concentrations of bone biochemical markers. Tumors with skeletal tropism generally lead to imbalance in bone metabolism induced by a number of cytokines secreted by tumor, stromal and bone cells. Recent studies suggest that the soluble receptor activator of NF-kB ligand (RANKL) and the macrophage inflammatory protein (MIP)-1a regulate the physiologic differentiation and activation of osteoclasts. In several tumors their altered secretion leads to hyperactive osteoclastogenesis and severe bone devastation. Multiple myeloma, a clonal plasma cell tumor, is characterized by its growth within the marrow and progressive erosion of bones by osteolytic lesions. We demonstrated that plasma cells directly secrete elevated amounts of RANKL and MIP-1a and degrade soluble osteoprotegerin (OPG), a decoy receptor of RANKL thus reducing its serum concentrations. Therefore, the increase of RANKL and MIP-1a may contribute to the excess of osteoclast activity. Measurements of RANKL, MIP-1a and OPG as markers of the bone pathophysiology can be useful for clinical management of the skeleton derangement present in several tumors.

La biologia molecolare dell’eritropoietina

R.A. Salvo, A. Mastrone, A. Spaccamiglio, L. Grasso, P. Borrione
Consorzio Piemontese Antidoping "Alessandro Bertinaria", Regione Gonzole, Orbassano, Torino

Biochimica Clinica: 2007; 31(3): 180-184 [Article in italian]

ABSTRACT. Molecular biology of erythropoietin. Erythropoietin (EPO) is a glycoprotein with a MW of about 30,000 Da. In adult humans, EPO is produced primarily by peritubular cells in the kidneys. The EPO gene has been found on human chromosome 7 (in band 7q21). EPO gene expression is induced by hypoxia-inducible transcription factors (HIF). It has a 165 amino acid chain with four oligosaccharide side chains and circulates in the blood at very low concentrations (~5 pmol/L). Clinical conditions that give rise to tissue hypoxia, including anaemia, lung disease or cyanotic heart disease, lead to increased concentrations of serum EPO. EPO acts by binding to a specific erythropoietin receptor (EPO-R) on the surface of red cell precursors in the bone marrow, stimulating them to transform into mature red blood cells. However, functional EPO-R have recently been demonstrated in various nonhemopoietic tissues indicating that EPO has a more pleiotropic action.

Valutazione dell’efficacia di raccomandazioni aziendali sulle strategie per l’impiego ottimale dei biomarcatori cardiaci ad un anno dalla loro introduzione

C. Valente, R. Dominici, A. Dolci, M. Panteghini
U.O. Laboratorio Analisi Chimico Cliniche, Ospedale “Luigi Sacco”, e Cattedra di Biochimica Clinica e Biologia Molecolare Clinica, Dipartimento di Scienze Cliniche, Università degli Studi, Milano

Biochimica Clinica: 2007; 31(3): 185-190 [Article in italian]

ABSTRACT. One-year audit of the implementation of protocols for optimal use of cardiac biomarkers in an Italian university hospital. Biochemical tests have a key role in the evaluation of cardiac disease. However, their overutilization and inappropriate requests create a heavy workload for laboratory and increased costs to the health care system. In 2005, we introduced new strategies for optimal use of cardiac biomarkers by practice guidelines devised by a multidisciplinary team. The adopted criteria, based on international recommendations, included information for requesting and interpreting cardiac troponin (cTn) for AMI rule-in/out and risk stratification, CK-MB mass for infarct size estimation and detection of post-PCI injury, and NT-proBNP for differential diagnosis of acute dyspnoea. One year after the implementation, a comprehensive audit was undertaken to evaluate the guideline effectiveness on test utilization and costs by comparing two one-year periods, one before (S1) and one after (S2) the protocol institution. The total test number was reduced from 201,090 to 135,017 (-33%). Myoglobin and CK-MB (as activity) were completely abolished in S2, whereas CK-MB mass showed a -87.7% reduction. No significant changes were observed for cTn (-2%), while a slight increase was demonstrated for NT-proBNP (1275 in S1 vs. 1614 in S2; +26.6%) reflecting its increasing usefulness in ED setting. The cTn workload in S2 was 14,540 tests, with 47.7% of requests coming from ED and a significant over-requesting (18.4% of total) by cardiac surgery division. Testing costs were reduced by € 104,871 per annum. This audit provided valuable information on the effective running of the newly introduced cardiac biomarker protocols indicating their efficacy in reducing inappropriate biomarker requests.

Metodologia KIMS: valutazione dei reagenti di Ia generazione per la misura di oppiacei e amfetamine e dei reagenti di IIa generazione per metadone, cocaina e cannabinoidi su analizzatore Hitachi 912

L. Marchioro, S. Ponchia, M. Plebani
Dipartimento di Medicina di Laboratorio, Azienda Ospedaliera di Padova

Biochimica Clinica: 2007; 31(3): 191-196 [Article in italian]

ABSTRACT. KIMS methodology: evaluation of 1st generation reagents for the measurement of opiates and amphetamines and IInd generation reagents for methadone, cocaine and cannabinoids on the Hitachi 912 analyzer. We evaluated reagents of Ist and IInd generation for the determination of several drugs of abuse in urine samples, based on the KIMS technique (Kinetic Interaction of Microparticles in a Solution). All determinations were performed on the Roche Hitachi 912 analyzer. We evaluated the imprecision, the functional reproducibility and the limit of detection of all parameters. We also determined the performance of methadone assay in comparison with results obtained for the reagent previously used (1st generation). In summary, we obtained good results for all the new KIMS reagents, with excellent performance characteristics.

Biochips e droghe d’abuso: valutazione del sistema Evidence in confronto con la metodologia KIMS

L. Marchioro*, A. Trombin, F. Castagna, S. Maietti, M. Plebani
*Dipartimento di Medicina di Laboratorio, Azienda Ospedaliera di Padova

Biochimica Clinica: 2007; 31(3): 197-204 [Article in italian]

ABSTRACT. Biochips and drugs of abuse: evaluation of the evidence system and comparison with kims methodology. We evaluated the analytical and diagnostic performances of a multiparameter technique (Evidence®). This is a new generation automatic analyser that employs biochips technology to determine drugs of abuse in urine samples. As comparison method, we used KIMS technology. The Evidence Drugs of Abuse assay panel is measured with an indirect chemiluminescent competitive immunoassay. DTRs (Discrete Test Regions) are generated on the biochip surface, where specific antibodies bind some substances of abuse: amphetamines, cocaine, barbiturates, cannabinoids, opiate, methadone, phencyclidine and benzodiazepines. A total of 322 urine samples were compared with the two technologies. 15 samples with significant differences between the two evaluated methods were assayed using the gas chromatography/mass spectrometry technique (GC-MS). The obtained results show a good analytical performance of Evidence that was found easy to use and very useful for laboratories with a medium-high workload.

Le non conformità del campione: modalità di registrazione e specifiche di qualità

M.S. Graziani, L. Mantovani, M. Nundini, P. Rizzotti
Laboratorio di Analisi Chimico-Cliniche ed Ematologiche, Ospedale Civile Maggiore, Azienda Ospedaliera di Verona

Biochimica Clinica: 2007; 31(3): 205-208 [Article in italian]

ABSTRACT. The sample non-conformities: registration and quality specifications. While clinical laboratories have traditionally been involved in the control of the analytical phase, there is emerging evidence that most errors occur in the pre-analytical phase. The sample non-conformities are the main cause of pre-analytical errors and the inappropriate specimen quality is the most frequent reason for sample rejection. We present here the procedures currently in use in our Laboratory to detect and register unsuitable samples. The sample non-conformities are detected either by instruments or by visual inspection and reported to the wards, by including in the reports codified comments. These are then retrieved from the Laboratory Information System and examined. In the year 2006 we received 811,534 samples for which we registered 11,681 non-conformities (1.4%). The most frequent unsuitable samples were hemolyzed (42%), followed by incorrect (24%) and clotted (17%) samples. The Intensive Care Units presented the largest number of non-conformities. When the number of non-conformities was expressed to the activity of the specific process, we registered 0.5% of clotted (haematology and coagulation) and 1.0% of hemolyzed samples (coagulation and chemistry). When the number was expressed as part per million of tests performed, we obtained 2147, 1263 and 887 for hemolyzed, incorrect and clotted samples, respectively. These figures are difficult to evaluate since data in the literature are neither abundant nor homogeneous. It is, therefore, important to encourage other laboratories to establish specific procedures for sample rejection in order to implement a reliable benchmarking.

L’inappropriatezza nella richiesta di esami di laboratorio per difetto di conoscenza. Errore individuale o errore di sistema?

A. Camerotto*, F. Formenton, E. Ramazzina, R. Di Liddo, F. Carmignoto
*Dipartimento di Patologia Clinica, Servizio di Medicina di Laboratorio, Rovigo

Biochimica Clinica: 2007; 31(3): 209-215 [Article in italian]

ABSTRACT. The inappropriate request for laboratory tests due to an imperfect knowledge. Individual or system error? The inappropriate request for diagnostic tests is a main problem in Laboratory Medicine, because of important implications on ethics, malapractice, risk management and costs. In this work, in order to analize this problem and suggest possible solutions, the whole error is considered imputable to both the individual error of the physician and the system error of the overall health system. Herein, it is discussed the clinician reasoning based on required knowledge during the diagnostic process to formulate a prescription, which is actually a free and conscious clinician choice. To this aim, tools for acquiring the scientific knowledge are described, as well as the individual and system problems that limit the effective use of information. We conclude that the inappropriate prescription is more properly defined as a logic system error, even if it could undoubtely arise from an individual error. At the end of a diagnostic process, the physician is not the responsible for the error but rather the heir of the system, which has not created the necessary conditions to have an accurate cognition when the prescription is required. Solutions are proposed for reducing the number of inappropriate requests. The opportunities coming from the Information Tecnology could permit a structural solution to the problem by means of using softwares that can drive prescriptions at the idoneous cognition level, as a necessary precondition for an actually consciuos and appropriate choice suitable to clinic needs.

Raccomandazioni per la rilevazione e la gestione dei campioni non idonei nei laboratori clinici

G. Lippi, G. Banfi, M. Buttarello, F. Ceriotti, M. Daves, A. Dolci, M. Caputo, D. Giavarina, M. Montagnana, V. Miconi, B. Milanesi, A. Mosca, M. Morandini, G.L. Salvagno
Gruppo di Studio Intersocietario SIBioC-SIMeL-CISMEL sulla Variabilità Extra-Analitica del Dato di Laboratorio

Biochimica Clinica: 2007; 31(3): 216-224 [Article in italian]

ABSTRACT. Recommendations for detection and management of unsuitable samples in clinical laboratories. A large body of evidence attests that quality improvement programs targeted at the sole analytical phase would not grant additional clinical and economical outcomes, since the large majority of errors encountered in clinical laboratories occurs in the extra-analytical areas of testing, especially in manually-intensive preanalytical processes. Most preanalytical errors result from system flaws and insufficient audit with the operators involved in sample collection and handling responsibilities, leading to an unacceptable number of unsuitable specimens due to misidentification, in vitro hemolysis, clotting, insufficient volume, wrong container and contamination. Detection and management of unsuitable samples are, therefore, necessary conditions to overcome this unwelcome variability. The present document is aimed to review the major causes of unsuitable specimens in clinical laboratories, providing consensus recommendations on detection and management.

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